Overall Survival In Pts Research Articles

Real-world (rw) treatment (tx) patterns and overall survival (OS) in patients (pts) with locally advanced/metastatic urothelial carcinoma (la/mUC) treated with avelumab first-line maintenance (1LM): Updated results from the SPEAR Bladder II study.

393 Background: Avelumab 1LM tx is approved in the US for pts with la/mUC who do not have disease progression after platinum-based chemotherapy (PBC). The tx landscape is evolving due to the recent approvals of newer therapies for pts with la/mUC. This study examines rw tx patterns, tx sequencing post avelumab 1LM, and OS in pts with la/mUC who initiated 1L tx in the US community oncology setting. Methods: This retrospective cohort study used the US Oncology Network (iKnowMed) EHR database. The study included adult pts (≥18 years) with la/mUC initiating 1L tx (index date) between Dec 1, 2019, and Nov 30, 2023. Pts were censored for OS at their last contact date or the end of study period, Feb 28, 2024. Descriptive statistics were used to describe tx patterns. Kaplan-Meier analysis was used to evaluate OS from the start of 1LM or second-line (2L) enfortumab vedotin (EV) treatment post avelumab 1LM. Results: A total of 1,658 pts with la/mUC initiated 1L tx with a median (range) follow-up of 9.0 months (0.1-50.4). The median (range) age at diagnosis was 73 years (31-90+), 74.7% were male and 47.1% had ECOG performance status ≤1. The 1L therapies included: IO monotherapy (41.2%), PBC only (32.4%), PBC followed by avelumab 1LM (11.2%), and other tx (15.1%). Since the US FDA approval (June 30, 2020), the utilization of avelumab 1LM among 1L PBC users ranged from 25.0% to 32.9% in 2023. Median (range) follow-up from the start of avelumab 1LM was 9.1 months (0.5-42.2). During the study observation period, 44 pts (23.7%) remained on avelumab 1LM. Median (95% CI) OS from start of avelumab 1LM was 18.5 months (13.8-23.8). Among the overall study cohort, 598 (36.1%) and 196 pts (11.8%) received 2L and third-line tx, respectively. The most common 2L therapies were IO monotherapy (44.1%) and EV monotherapy (23.9%). After discontinuation of avelumab 1LM, 81 pts (43.5%) received 2L tx, 48 (59.3%) of those received EV; median OS from start of 2L EV was 12.7 months (7.2-16.5). Conclusions: These rw study findings demonstrate avelumab 1LM effectiveness for pts whose disease has not progressed on 1L PBC and provides evidence of the use of 2L EV after avelumab 1LM. There was an increased uptake of avelumab 1LM since its FDA approval. Survival outcomes are consistent with the JAVELIN Bladder 100 clinical trial and other rw studies that had shorter follow-up. We observed high IO monotherapy use despite the platinum-ineligible population typically making up 11% of pts with la/mUC. 1 Some of these pts treated with IO monotherapy may benefit from alternative 1L regimens. Future rw studies are needed to further characterize contemporary tx patterns, optimal tx sequencing, and survival in pts with la/mUC amidst the evolving tx landscape. 1 Gupta S, et al. JNCI 2024;116(4):547–554.

The correlation between L1CAM expression and outcomes in patients with metastatic colorectal cancer treated with first-line chemotherapy.

95 Background: L1CAM is a cell adhesion molecule and stem cell marker belonging to the immunoglobulin superfamily of cell adhesion molecules (IgCAMs). L1CAM may be aberrantly expressed in several types of human tumors. The aim of the present study was to evaluate the correlation between L1CAM expression and outcomes in patients with metastatic colorectal cancer. Methods: We retrospectively collected data from 51 mCRC pts treated between 2017 and 2022 at the Medical Oncology Unit of the University Hospital of Cagliari. Tumor samples were retrospectively tested for L1CAM immunohistochemical (IHC) expression with the aim of evaluating the correlation with clinical outcome in terms of overall survival (OS) and progression-free survival (PFS). The primary endpoint was the mOS while secondary endpoint was mPFS. The aim of the present analysis was to evaluate the role of L1CAM expression in tumor cells in predicting the clinical outcome of CRC patients treated with standard chemotherapy. Statistical analysis was performed with the MedCalc Statistical Sofware Version 14.10.2. Results: Median age was 70 (±13), 58.8% were males and 41.2% were females. 29.4% of pts had carcinoma of the right colon, 39.2% left colon and 31.4% rectum. Negative or weak L1CAM score 0 was observed in 39.2% patients; 43.1% pts showed a score 1+; 11.8% showed score 2+, and 5.9% showed score 3+. Positivity for L1CAM correlated with a worse prognosis. The median OS for pts not expressing L1CAM was 74.0 months versus 32.0 for patients expressing the biomarker ( p = 0.0021). The mPFS for patients not expressing L1CAM was 21.0 months, vs 6.0 for patients expressing the biomarker ( p = 0.0066). The same negative correlation on outcomes was shown based on the degree of L1CAM expression. A different L1CAM score corresponded to a different OS and PFS. Pts with score 0 showed a mOS of 74 months vs 37 and 18 months for scores 1+ and 2+/3+, respectively ( p < 0.0001). Similar results were obtained with the mPFS: patients with score 0 showed a median of 21 months vs 8 and 2 months for scores 1+ and 2+/3+, respectively ( p = 0.0138). Conclusions: L1CAM expression in cancer cells correlates with a worse prognosis in mCRC patients. Immunohistochemical evaluation of this biomarker could allow the identification of a subgroup of patients capable of benefiting from a targeted therapy.

Atezolizumab versus placebo in combination with bevacizumab and non-platinum-based chemotherapy in recurrent ovarian cancer: Final overall and progression-free survival results from the AGO-OVAR 2.29/ENGOT-ov34 study.

LBA5501 Background: Paclitaxel or pegylated liposomal doxorubicin (PLD) in combination with bevacizumab (bev) are standard treatment options in patients with relapsed ovarian cancer not candidates for platinum, but responses are usually short-lived. Recently, two trials have reported a numerical but non-significant advantage from the addition of atezolizumab (atezo) to chemo plus bev in the recurrent setting (ATALANTE, Kurtz JE et al., J Clin Oncol & NRG GY009, O'Cearbhaill et al, IGCS 2023). AGO-OVAR 2.29 investigated the efficacy of atezo in combination with bev and non-platinum-based chemo. Methods: AGO-OVAR 2.29 is a randomized, double blind, phase III trial evaluating the efficacy and safety of atezo plus bev and chemo in patients (pts) with recurrent ovarian cancer. Eligible patients had a 1st/2nd relapse within 6 months after completing platinum-based chemo or a 3rd relapse regardless of treatment-free interval. A fresh biopsy for central PD-L1 testing (VENTANA SP142 assay) prior to randomization was mandatory. All pts received weekly paclitaxel or PLD and bev until disease progression or intolerable toxicity and were randomized 1:1 to either atezolizumab 840 mg q14 days or placebo until progression or for a maximum duration of 24 months. Number of prior lines, planned chemo, prior bev and PD-L1 status served as stratification factors. Overall survival (OS) and progression-free survival (PFS) in the intention to treat (ITT) population were primary endpoints, both to be analyzed after observation of 391 deaths. Data cut-off (DCO) occurred on 26/01/2024. OS and PFS analysis is based on a multiple Cox regression with treatment arm and stratification factors as covariates. Safety is reported for pts who received at least one dose of study treatment. Results: 574 pts were randomly assigned to atezo (285) or placebo (289). 45.1% received PLD and 53.7% paclitaxel. 7 pts did not start study treatment. 36.1% of pts had received 3 prior lines and 72.5% prior bev. 25.8% were PD-L1 positive. At DCO 418 OS and 505 PFS events have occurred. Median OS was 14.3 months (mos) in the atezo and 13.0 mos in the placebo arm (HR 0.83, 95% CI 0.68-1.01; p=0.06) and PFS 6.3 mos for atezo vs 6.6 mos for placebo arm (HR 0.88, 95% CI 0.73-1.05; p=0.15). Similar HR were observed in PD-L1 positive and negative pts. In total, 580 SAE and 141 AESI were reported. AEs of ≥ grade 3 were reported in 71.5% in the atezo and 68.9% in the placebo arm. 63.7% of pts in the atezo and 51.4% in the placebo arm experienced serious AEs. Conclusions: The addition of atezo to chemo plus bev did not significantly improve OS or PFS in pts. with recurrent ovarian cancer who are no candidates for platinum. Safety was within the expected range. Translational research is ongoing. Clinical trial information: NCT03353831 .

Use of baseline and serial ctDNA dynamics to predict outcomes in patients treated with first-line tebentafusp, including those who were and were not treated beyond progression.

9536 Background: Tebentafusp (tebe), a bispecific soluble T cell receptor specific for a gp100 peptide, is licensed for the treatment of metastatic uveal melanoma (mUM) in HLA-A*02:01+ individuals. As part of the pivotal, Phase 3 IMCgp100-202 study, 378 mUM pts were randomized to receive tebe or investigators choice. Approximately 60% of patients (pts) with metastatic UM in the IMCgp100-202 study had detectable baseline ctDNA. We have reported the strong relationship between change in ctDNA at 9 weeks (wks) and overall survival (OS). Additionally, radiographic treatment response is a poor predictor of who is benefitting from therapy. We hypothesized that ctDNA dynamics would help identify those patients (pts) who benefit from treatment beyond progression (TBP). Methods: Sera (n=202 pts) collected at baseline and wk 9 on tebe were analyzed for ctDNA using a targeted mPCR-NGS assay for 15 genes including GNAQ, GNA11, SF3B1, PLBC4, EIF1AX, and CYSLTR2. RECISTv1.1 was assessed by investigators; TBP was allowed per protocol. OS was analyzed in subsets of pts who were not TBP, and those who were TBP and treated with tebe for < or > 16 wks; the approximate time point where TBP pts would have had confirmatory imaging, although confirmatory scan data is not available. At baseline, pts were determined to be ctDNA detectable or undetectable. At wk 9, pts were determined to have cleared ctDNA, < or ≥ 68% (0.5 log-fold) reduction, < or ≥ 50% reduction. Data cut-off was July 2023. Results: Of 202 pts randomized to tebe and with ctDNA at baseline and wk 9, 126 (62%) received TBP (80 <16 wks, 46 ≥ 16 wks). Undetectable ctDNA at baseline was associated with improved OS regardless of TBP, while TBP was associated with improved OS in those with baseline detectable ctDNA (hazard ratio, HR, 0.59, 95% confidence interval, CI, 0.4-0.88). Subgroup analysis of those with baseline detectable ctDNA demonstrated improved OS in only those who received TBP for ≥ 16 wks (HR 0.33; 95% CI 0.21-0.51). Clearance of ctDNA at wk 9 was associated with better OS than in those who did not have clearance. TBP was associated with better OS in pts who did not have clearance (HR 0.48, 95% CI 0.30-0.79), but not in those with clearance (HR 0.87, 95% CI 0.43-1.78). Finally, TBP was associated with improved outcomes in pts with ≥50% and ≥68% reduction, compared to those without reduction, HR 0.63 (95% CI 0.4-0.97) and 0.62 (95% CI 0.39-0.99), respectively. Conclusions: Baseline and wk 9 ctDNA detection predicts OS in mUM pts treated with first line tebe. The utility of ctDNA predicting pts most likely to benefit from TBP is less clear, although TBP seems to be more beneficial in those with reduction of ctDNA at wk 9. Optimization of time points, assay, and integration of ctDNA data with radiomics are necessary to understand the true utility of ctDNA in helping select which pts should receive TBP. Clinical trial information: NCT03070392 .

Clinical characteristics and treatment outcomes in Hispanic/Latino patients with advanced renal cell carcinoma at a single institution.

e13738 Background: The incidence of renal cell carcinoma (RCC) is increasing, with an expected 81,610 new cases and 14,390 deaths in 2024. While clinical characteristics in patients with RCC have been well described, studies focusing on minority patients, such as Hispanic and Latino (HL), are limited. The objectives of the current study are to analyze differences in clinical, pathological, and outcome characteristics between HL and non-Hispanic Latino (NHL) pts. with advanced RCC (aRCC) in South Florida. Methods: We retrospectively reviewed clinical and pathological data from pts. with aRCC treated at Sylvester Comprehensive Cancer Center (SCCC) from 2010 to 2023. Descriptive statistics were used to summarize demographic and baseline characteristics. HL vs. NHL groups were compared using chi-square or Fisher’s exact test for categorical variables, and Wilcoxon rank-sum test for continuous variables. Time-to-event outcomes including metastasis-free survival (MFS) and overall survival (OS) were estimated using Kaplan-Meier method, and two groups were compared using the log rank rest. Results: A total of 417 patients diagnosed with aRCC who received care at SCCC were analyzed. HLs comprised 45% while NHLs represented 55% of patients with aRCC. A higher proportion of HLs presented at an earlier age (< 60y.o, 53% vs. 44%), were female (31% vs. 24%), and had a higher proportion of ISUP grade 4 tumors (47% vs. 34.8%). HLs had a significantly shorter metastasis-free survival (HR 1.48 [95% CI: 1.06-2.05]) compared to NHLs. There were no differences in the frequency of AEs from TKI, IO or IO-TKI based therapies between HLs and NHLs. HLs were less likely to achieve an objective response (CR/PR) to 1st-line therapy compared to NHLs (OR 0.54 (95% [CI: 0.31-0.94]), including HLs with non-ccRCC (OR 0.24 [95% CI: 0.07-0.81]). There was no significant correlation between ethnicity and overall survival in pts. treated with systemic therapy. HLs were less likely to achieve CR/PR to 1st-line therapy compared to NHLs (OR 0.54 [95% CI: 0.31-0.94, p=0.030]) in 217 pts. treated with 1st-line therapy, and in 55 with non-cc RCC (OR 0.24 [95% CI: 0.07-0.81, p=0.021]). There was no significant correlation between ethnicity and overall survival in pts. treated with systemic therapy. Conclusions: In our cohort, patients with aRCC presented at an earlier age and we had a higher proportion of females in HLs compared to NHLs. HLs had a higher risk of developing metastases after nephrectomy compared to NHLs and were less likely to achieve an objective response to 1st-line systemic therapy. Our results, suggesting a potentially more aggressive clinical course of aRCC in HLs in our patients, need further validation in a larger cohort. Future studies will incorporate analysis of molecular tumor characteristics, to further understand biological differences explaining outcomes observed in HL vs NHL populations with aRCC.

Long-term survival outcomes of patients (pts) with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) treated with brexucabtagene autoleucel (brexu-cel) in ZUMA-3.

6531 Background: Brexu-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for pts ≥18 y with R/R B-ALL in the US (≥26 y in the EU). In the 3-y follow-up of ZUMA-3, median overall survival (OS) was 25.6 mo (N=78). Survival benefit was seen regardless of age, prior treatment, or subsequent allogeneic stem cell transplant (sub alloSCT) status (Shah et al. ASCO 2023. #7023). Here we report 4-y survival outcomes for ZUMA-3. Methods: Eligible pts (≥18 y) had R/R B-ALL and received brexu-cel (1×106 CAR T cells/kg) after leukapheresis and lymphodepleting chemotherapy. The primary endpoint was overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate per independent review with OS as a key secondary endpoint. Descriptive statistics are reported for post hoc exploratory subgroup analyses. Results: As of July 23, 2023, median follow-up time in Phase 1 and 2 pts who received the pivotal dose of brexu-cel (N=78) was 53.6 mo (range 44.7-82.3). Median OS (95% CI) was 25.6 mo (16.2-60.4) in all treated pts and 47.0 mo (23.2-not estimable [NE]) in pts with CR/CRi (n=57). In pts <26 y (n=15), median OS (95% CI) was 23.2 mo (9.0-NE) and was 26.0 mo (15.9-NE) in pts ≥26 y (n=63). Median OS (95% CI) in pts with 1 prior therapy (n=15) was 60.4 mo (7.6-NE) and was 25.4 mo (15.9-47.0) in pts with ≥2 prior therapies (n=63). Medians for OS (95% CI) in pts with (n=38) and without (n=40) prior blinatumomab (blina) were 15.9 (8.3-26.0) and 60.4 mo (18.6-NE), respectively. Median OS (95% CI) was 36.3 mo (10.2-NE) in responders who went on to sub alloSCT (n=14) and 60.4 mo (23.2-NE) in those who did not (n=43). The 48-mo OS rate was 40% (95% CI, 28-52) in all pts but appeared lower in pts with prior blina (24%; Table). No new adverse events or deaths occurred since the prior analysis. Grade ≥3 infection rates since the start of study appeared higher in pts <26 y and in pts with prior blina (Table). Rates of non-relapse mortality (NRM) and relapse-related mortality (95% CI) at 48 mo were 25% (15-37) and 34% (24-45; N=78), respectively. Of note, 6/17 NRM events (35%) occurred in pts with sub alloSCT. Conclusions: After >4 y follow-up, pts in ZUMA-3 continued to experience OS benefit regardless of age, prior therapy, or sub alloSCT status, though pts with prior blina had a numerically lower 48-mo OS rate. Small subgroups and unbalanced pt characteristics limit interpretation of these results. No new safety signals were observed. Further studies are needed to fully assess the impact of age, prior therapies, and sub alloSCT on outcomes after brexu-cel. Clinical trial information: NCT02614066 . [Table: see text]

Effect of tumor burden on survival in patients with stage IV EGFR-mutant NSCLC receiving osimertinib monotherapy.

8611 Background: Osimertinib (osi) has traditionally been given as monotherapy for patients (pts) with stage IV EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC), although acquired resistance remains a challenge. Recent data from the FLAURA2 study demonstrated a progression free survival (PFS) benefit of approximately 9 months (mos) when osi is combined with platinum-pemetrexed chemotherapy. Despite this improvement, combination therapy is associated with higher rates of adverse events, making it challenging to decide which pts should receive TKI + chemo vs TKI monotherapy. Tumor burden (TB) in pts with stage IV EGFRm NSCLC, which may be associated with risk of developing resistant clones on TKI monotherapy, and its association with clinical outcomes has not been examined. Methods: Retrospective, single institution manual case review of pts who received osi monotherapy. Primary objectives were PFS (i.e., oligoprogression requiring local therapy, disease progression (PD) with osi discontinuation, or death) and overall survival (OS) related to extent of TB. Those who did not receive osi monotherapy for stage IV EGFRm NSCLC or discontinued osi for reasons other than PD were excluded. Demographics, comorbidities, performance status, PD-L1 expression, histology, EGFRm subtype, prior TKI use, total number of visceral tumors (TTn), and total number/sites of metastatic disease (MDn) collected for analysis. Extent of TB categorized by TTn (1-4, 5-9, ≥10) and MDn (1-2, 3-4, ≥5). PFS and OS estimated by Kaplan-Meier method and compared using log-rank test. Results: 325 pts eligible for analysis. Median follow-up time was 22.7 mos. Median PFS (mPFS) for the overall cohort was 16.3 mos (95% CI; 13.7 - 18.9) and median OS (mOS) was 31.1 mos (95% CI; 27.4 - 39.3). Pts with a TTn of 1-4 had significantly better mPFS compared to those with a TTn of 5-9 and ≥10 (mPFS: 21.5 vs 16.3 vs 13.4 mos, respectively; P = 0.001). Pts with a TTn ≥10 had significantly worse mOS compared to those with a TTn of 5-9 and 1-4 (23.7 vs 35.1 vs 57.7 mos, respectively; P < 0.0001). Similarly, pts with a MDn of 1-2 had significantly better mPFS and mOS compared to those with a MDn of 3-4 and ≥5 (mPFS: 21.6 vs 11.4 vs 9.0 mos, respectively [P < 0.0001]; mOS: 44.3 vs 20.8 vs 22.4, respectively [P < 0.0001]). Pts with liver and bone mets had significantly worse mPFS and mOS, whereas those with lung and brain mets had worse mOS without affecting PFS. Conclusions: The extent of baseline TB, categorized by TTn and MDn, impacts both PFS and OS in pts with stage IV EGFRm NSCLC treated with osi monotherapy. Pts with “low-TB” (i.e., TTn 1-4, MDn 1-2) appear to have a survival advantage compared to those with “intermediate- or high-TB” (i.e., TTn 5-9 and ≥10, MDn 3-4 and ≥5) and may derive less benefit from the addition of chemotherapy to osi. Prospective, matched real-world treatment cohorts are warranted to optimize treatment strategies for this patient population.

Impact of body mass index and karyotype on clinical outcomes in adolescents and young adults (AYA) with acute myeloid leukemia.

6551 Background: Acute myelogenous leukemia (AML) represents 15%–20% of leukemias in children and approximately 33% in adolescents and young adults (AYA) (1). Obesity has been associated with worse outcome in acute lymphoblastic leukemia in AYA patients (pts). To date, however, the relationship between weight and clinical outcomes in AYA pts diagnosed with AML has not been established. We investigated the impact of body mass index (BMI) along with other prognostic factors on outcomes of AYA AML pts receiving intensive chemotherapy and/or allogeneic stem cell transplant (SCT). Methods: This retrospective chart review included pts 18-39 yrs newly diagnosed with AML between 01/2006-12/2023. All pts received intensive chemotherapy with cytarabine- and anthracycline-based induction followed by consolidation chemotherapy +/- SCT. BMI was calculated using height and weight at AML diagnosis. Pts were classified by BMI into under, normal, overweight, or obese categories. AML risk classification (ELN 2022) and HCT co-morbidity index (HCT-CI) were performed. Outcomes included complete response (CR), CR with incomplete counts (CRi), overall response rates (CR+CRi), event free survival (EFS), and overall survival (OS). Results: Eighty-seven pts (median age 25 yrs, range 18-38) were identified. 44 (51%) were male; 85% were Caucasian. Per ELN 2022, 27 (31%) had favorable, 40 (46%) intermediate, and 20 (23%) adverse risk. Overall response rate to chemotherapy was 92% (CR 80%, CRi 12%). CR rate by ELN was 96%, 72% and 58%, respectively. Median OS for all pts was 788 days and per ELN risk was 1379, 569, and 595 days, respectively. Co-morbidity indices (HCT-CI) ranged from 0-5. Sixty-two percent underwent SCT. 29% relapsed. The percentage of pts alive at 2 and 5 years was 54% and 29%. Pts were categorized by BMI: underweight (BMI < 18.5, 6%), normal weight (NW) (BMI 18.5-24.9) (37%), overweight (OW)(BMI 25-29, 26%), and obese (OB) (BMI > 30, 31%) pts. Overall, there was a trend to improved outcomes in NW vs OW and OB pts. Median OS was 1006 (NW) vs 748 (OW) vs 678 (OB) days (p=0.0036 for NW vs OW/OB). Two-year OS was 63%, 52%, and 48%; 5-year OS was 38%, 26%, and 19%. The impact of BMI was dependent on AML karyotype. In favorable risk AML AYA pts, the relapse rate was 4%, 4% and 12%. Median OS was 1982 (NW), 1169 (OW), and 1256 (OB) days (p=0.0525 NW vs OW/OB). Five-year OS was 50%, 25% and 18%. The most common causes of death were GVHD-induced multi-organ failure and respiratory failure which did not correlate with HCT-CI. In intermediate and adverse risk AML, there was no difference in outcomes by BMI. Conclusions: Outcomes of favorable risk AYA AML pts following intensive chemotherapy +/- SCT was influenced by BMI with increased mortality and shorter OS in pts with high BMI (overweight and obese) as compared to normal BMI. Additional studies to confirm this finding and elucidate the underlying reasons are warranted.

Effectiveness and toxicity of multidisciplinary treatment of head and neck cancer among people with HIV: Real-world evidence from a tertiary cancer center in Brazil.

e24139 Background: The incidence of head and neck squamous cell carcinoma (HNSCC) is rising among people with HIV (PWH). Previous studies have shown an increase in treatment-related toxicities in this population. This study aims to determine the demographics and treatment outcomes in this patient group at a tertiary cancer center in Brazil. Methods: HNSCC patients (pts) with HIV diagnosis treated at our institution between 2009 and 2022 were included. Medical charts were analyzed to extract clinical data. Log rank was used to compare survival estimates and stratified Cox regression model was used for univariate and multivariate analyses. Results: Our search identified 75 pts with HIV among 5956 pts with HNSCC. Median age at cancer diagnosis was 53 years (IQR 49-59.5), 80% were male and 82.7% had a smoking history. Most pts had an oropharynx primary tumor (38.7%) and locally advanced disease (80%), with T3 and T4 tumors in 55 pts (73.3%) and N+ in 48 pts (64.1%). A feeding tube (FT) was placed in 32% of pts before treatment. HIV viral load was detectable in 23 (30.7%) pts and 19 (25.3%) had a CD4 count of fewer than 200 cells/mm³, while 97.3% of the pts were on combination antiretroviral therapy at the time of HNSCC diagnosis. 26 pts were operated with curative intent and 20 pts received adjuvant therapy. In the total population, concurrent cisplatin-based chemoradiation (CCRT) was prescribed to 26 pts (34.7%) and 34 (45.3%) received radiotherapy (RT) alone. 65.4% of the pts in the CCRT group and 20.6% in the RT group were unable to complete treatment as prescribed, mostly due to toxicity. No pts with positive viral load or CD4 < 200 cells/mm³ were able to complete CCRT. Treatment toxicity led to hospitalization in 24% of pts and 7 pts needed FT placement. There were 8 deaths during treatment, 5 in pts with CD4 < 200 cells/mm³. Positive viral load was associated with CCRT interruption (p = 0.03) and a CD4 count of less than 200 cells/mm³ increased the risk of death during treatment (p = 0.02). Median overall survival (OS) was 31.7 months (IQR 14.6-53.7). Multivariate analysis did not show a statistically significant decrease in OS in pts with positive viral load or CD4 < 200 cells/mm³. Factors associated with worse OS on multivariate analysis were FT usage (HR = 2.91; 95% CI: 1.45-5.83) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) greater than 1 (HR = 3.26; 95% CI: 1.46-7.24). Conclusions: HNSCC treatment in PWH is associated with a high discontinuation rate, even in pts with antiviral therapy. High toxicity rates and deaths during treatment were observed. Positive viral load and low CD4 count were considered contributing factors. ECOG-PS and enteral feeding tube usage were independently associated with worse survival. The development of more tailored strategies in this population is needed to improve outcomes in patients with HNSCC and HIV.

Avelumab + axitinib vs sunitinib in patients (pts) with advanced renal cell carcinoma (aRCC): Final overall survival (OS) analysis from the JAVELIN Renal 101 phase 3 trial.

4508 Background: The JAVELIN Renal 101 (NCT02684006) phase 3 trial compared first-line treatment with avelumab + axitinib vs sunitinib in aRCC. The trial previously met one of its primary objectives by showing significantly longer progression-free survival (PFS) with avelumab + axitinib vs sunitinib in pts with PD-L1+ tumors; longer PFS, higher objective response rate (ORR), and an acceptable safety profile were also observed in the overall population. OS data were immature. Here we report the final analysis. Methods: Pts with untreated aRCC (any IMDC risk score) were randomized 1:1 to avelumab + axitinib or sunitinib. OS and PFS (by blinded independent central review) in pts with PD-L1+ tumors (SP263 assay) were independent primary endpoints. OS and PFS in the overall population were key secondary endpoints; response and safety were also analyzed. Results: Of 886 pts randomized, 560 (63.2%) had PD-L1+ tumors. At data cutoff (August 31, 2023), median follow-up in the avelumab + axitinib and sunitinib arms was 73.7 and 73.6 months, respectively (≥68 months in all pts). Final efficacy data are shown in the Table. In the avelumab + axitinib and sunitinib arms, grade ≥3 TRAEs occurred in 66.8% vs 61.5%, respectively. Second-line therapy was received by 58.1% vs 69.4%, including a PD-(L)1 inhibitor in 18.8% vs 53.6%, respectively. Conclusions: The JAVELIN Renal 101 trial provides the longest follow-up for immune checkpoint inhibitor + tyrosine kinase inhibitor combination treatment from a phase 3 trial reported to date. OS analyses favored avelumab + axitinib vs sunitinib but did not reach statistical significance. PFS was longer with avelumab + axitinib vs sunitinib, and responses were durable in a subset of pts. Final analysis results confirm the long-term efficacy and manageable safety profile of avelumab + axitinib treatment in pts with aRCC. Clinical trial information: NCT02684006 . [Table: see text]

Comparison of chemotherapy to chemo-immunotherapy as first-line treatment in patients with advanced large cell neuroendocrine carcinomas (LCNECs) of mixed histology: A multi-institutional international retrospective study.

8602 Background: LCNECs are a rare subtype of lung cancer, with limited clinical trial data and an unclear consensus on first-line treatment. Even less is known about the optimal treatment approach for pts with mixed LCNECs, a pathologic subtype where tumors contain both LCNEC histology as well as features of adenocarcinoma, squamous cell, or small cell lung cancer. Methods: We conducted an international multi-institutional retrospective analysis (n=13 institutions) of pts with advanced or metastatic mixed LCNECs who received 1st-line systemic therapy with either chemotherapy alone (chemo) or chemo-immunotherapy (chemoIO) between 2010-2023. Clinical outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (trAEs). Survival comparisons were made via the log-rank test. Results: Seventy-three pts with mixed LCNECs received either chemo (n=42, 57.5%) or chemoIO (n=31, 42.5%). The most common chemo regimens were carboplatin/etoposide (n=27) and cisplatin/etoposide (n=8), while the most common chemoIO was carboplatin/etoposide/atezolizumab (n=19). Median age at 1st-line therapy initiation was 65 (IQR: 60-72). 64% of pts were male (n=47). The majority were former smokers (n=41, 56.2%), with 22 current smokers (30.1%), and 10 non-smokers (13.7%). Mixed histologies included LCNEC/NSCLC (n=45, 56.2%), LCNEC/SCLC (n=17), LCNEC/carcinoid (n=1), and unspecified mixed LCNEC (n=10). Median PFS for chemo was 5 months (95% CI 2.7-9.2) vs. 6 months (95% CI 4.4-8.3) for chemoIO ( p=0.86). Median OS for chemo was 14.2 months (95% CI 10.4-22.5) vs. 17.2 months (95% CI 9.4-27.2) for chemoIO ( p=0.66). The ORR did not differ between chemo (n=18, 45%) and chemoIO (n=15, 48.4%) ( p=0.81). In the chemo group, 60% (n=25) experienced trAEs of any grade, with 23.8% (n=10) experiencing grade 3+ events and four requiring hospitalizations. For chemoIO pts, 61% (n=19) experienced trAEs, with 25.8% (n=8) experiencing grade 3+ events and six requiring hospitalizations. Neutropenia was the most common grade 3+ trAE for both chemo (n=5) and chemoIO (n=4). Overall, there were no significant differences between chemo or chemoIO groups for ORR ( p=0.81), all-grade trAEs ( p=0.88), grade 3+ trAEs ( p=0.84), PFS ( p=0.86), or median OS ( p=0.66). There were no significant differences in median PFS ( p=0.46) or OS ( p=0.99) for pts with mixed LCNEC/NSCLC vs. LCNEC/SCLC. Conclusions: For mixed LCNECs, there was no significant difference in PFS or OS between first-line treatment with chemo vs. chemoIO, suggesting limited benefit from immunotherapy for these pts. Additionally, survival outcomes did not differ between mixed LCNEC/NSCLC and LCNEC/SCLC, suggesting a biology primarily driven by their neuroendocrine component.

Frailty risk assessment and impact on acute myeloid leukemia outcomes (FRAIL-AML): A population-based study from Ontario, Canada.

6506 Background: In acute myeloid leukemia (AML), treatment decisions, specifically intensive versus non-intensive approaches, depend on the clinician’s assessment of patient fitness. Frailty as a measure of fitness is a broader concept than commodities and is associated with worse outcomes in many cancers. Frailty assessment is incorporated to provide the precision to oncology treatment selections in addition to disease-related factors. The impact of frailty on outcomes in AML is not well studied. Methods: This retrospective cohort study from population-based health administrative databases in Ontario, Canada (ICES) included all patients (pts) ≥18 years diagnosed with AML between 2006 and 2021, treated within 90 days after diagnosis. Frailty was measured using McIsaacs’s frailty index (MFI)- a validated tool. Progressively increasing tertiles of MFI were categorized as fit (FT), pre-frail (PFR), or frail (FR). Treatment intensity was classified as intensive (IT) or non-intensive (NIT) based on standard practices. The primary outcome was overall survival (OS). Association of frailty with OS was measured using Cox regression separately for IT and NIT AML. Results: Out of 5450 pts, with a median age of 65 (IQR 54-74), 55.8% were males and 44.2% were females. 65% (n=3543) received IT, out of which 29.4% and 35.5% pts were FR and PFR respectively. Remaining 35% (n=1907) received NIT, with 41.1% and 32.3% pts being FR and PFR. Median overall survival in months (OS, 95% CI) for the entire group, IT, and NIT were 12.5 (12.0-13.2), 16.7 (15.7-18.2), and 7.6 (7.0-8.2), respectively. OS (table) was notably lower in FR pts compared to fit pts (p<0.0001) in both IT and NIT. Univariate and multivariate analyses identified frailty, advanced age, and previous non-AML malignancy as risk factors associated with worse OS in both IT and NIT groups (table). Conclusions: Higher frailty is independently associated with worse OS in AML pts after adjusting for advanced age. A substantial proportion of AML pts in both IT and NIT groups exhibit a mismatch in treatment intensity assignments based on their frailty status, with about 30 % FR pts receiving IT and over 25 % FT pts receiving NIT. This study sheds light on the need for frailty evaluations using standardized tools to optimize treatment decisions in AML pts. [Table: see text]

Effects of socioeconomic status (SES) and healthcare resource (HCR) availability on survival in Black patients (pts) versus (vs) White pts with multiple myeloma (MM): A SEER Medicare analysis.

e13678 Background: In MM, disparities exist for overall survival (OS) by race, and many factors may contribute to these differences. This study evaluates whether SES and HCR availability impacts OS in older pts with newly diagnosed MM (NDMM) based on race. Methods: This retrospective study used linked SEER-Medicare claims (diagnosis [Dx] 6/1/2013–12/31/2017) and Area Health Resource Files (AHRFs; from 2018) to identify non-Hispanic White and non-Hispanic Black pts aged ≥66 years with NDMM. AHRFs included county-level HCR availability data (e.g. number of long-term hospital beds, medical doctors [MDs]). Continuous Medicare A and B enrollment until 12/31/2019 or preceding death was required. Pts with other cancers, Dx from death data, missing county information and enrollment in health maintenance organizations or clinical trials were excluded. Kaplan-Meier was used for unadjusted median OS and Cox proportional hazards for OS risk by race. Age, sex, race, Charlson Comorbidity Index (CCI), poverty, education, and HCR availability were included in the adjusted mixed effects Cox model. Results: We identified 6,609 pts with NDMM; 15.6% were Black. For Black pts vs White pts, median age at Dx was 76 vs 77 years, 57.1% vs 46.0% were female, and mean CCI was 2.1 vs 1.4 (p<.001 for all). Within census tracts, mean percentage of pts living under the poverty line and received <12 years of education was 21.2% vs 11.3% (p<.001) and 19.0% vs 11.3% (p<.001) for Black pts vs White pts, respectively. Unadjusted median OS for Black pts vs White pts was 2.76 vs 3.01 years (hazard ratio [HR]: 1.08; p=.063). In the adjusted model, several SES and HCR availability factors were significant. OS HR by race reversed directionality when adjusted for demographics, SES and HCR availability, but this was not significant (HR: 0.92; p=.12; Table). Conclusions: We found that Black pts with NDMM in SEER-Medicare claims were younger, had higher CCI, completed less education, and were more likely to live in census tracts with higher poverty percentages vs White pts. Several factors relating to SES and HCR availability significantly influenced OS and may drive disparities in care. Further research on larger datasets is needed to better understand these disparities. [Table: see text]

Overall survival (OS) in a u.s. Asian population with stage IV NSCLC with EGFR mutations treated with first-line (1L) osimertinib (Osi) compared to earlier generation (Gen) of TKIs or sequential treatment (Tx).

e20597 Background: Osi, a 3rd-gen EGFR tyrosine kinase inhibitor (TKI), was approved as 1L tx for metastatic non-small-cell lung cancer (NSCLC) with EGFR mutations (ex19del or L858R) in 2018. This was based on the FLAURA trial, showing improved progression-free survival and OS of 1L osi compared to 1st-gen TKIs. Despite this, subgroup analyses revealed no OS difference in Asian or L858R patients (pts). Studies such as GioTag and UpSwinG showed better median OS in Asians with ex19del mutations on sequential afatinib and osi tx, prompting the question if sequencing of tx may also benefit L858R pts. We conducted this analysis of real-world outcomes in U.S. Asian pts with EGFR mutated NSCLC treated with 1L osi, 1st- or 2nd- gen TKIs (prior-TKIs-only), or sequential 1st- or 2nd- gen TKI followed by osi (sequential-TKI-osi). Methods: We conducted a single-institution IRB-approved retrospective study at NYU, including Asian pts diagnosed with stage IV NSCLC with EGFR ex19del or L858R, who received any gen of TKIs from 1/1/2010 to 1/13/2023. We compared 3-year (3y) OS based on tx and mutation subtypes, excluding pts with less than 3 years of follow-up. The analysis utilized the Cox proportional-hazards model to calculate hazard ratios (HR) and P values of OS. Survival curves were estimated using the Kaplan-Meier method. The log-rank tests were used to assess survival differences between tx groups. Additionally, a multivariable Cox proportional-hazards model explored the association between pts' survival time and multiple predictor variables. Results: We analyzed 139 cases: 103 (74%) females, 68 (49%) L858R, 113 (81%) never smokers, and age 31-96 years. The 3y OS analysis revealed no significant difference in the OS in L858R pts who received prior-TKIs-only (p = 0.83) or sequential-TKI-osi (p = 0.90), compared to 1L osi (median OS not reached in all three groups). However, in ex19del pts, prior-TKIs-only (HR 0.31, 95% CI 0.13-0.76) and sequential-TKI-osi (HR 0.30, 95% CI 0.11-0.85) txs showed superior OS compared to 1L osi, with a median OS of 24.7 mo in 1L osi and not reached in other two txs. Among all predictor variables (tx, age, sex, EGFR subtypes, and smoking status), only age had a significant but small impact on OS (HR 1.03, 95% CI 1.01-1.06). Conclusions: Our real-world analysis revealed that Asian stage IV NSCLC pts with L858R treated with 1L osi had a similar 3y OS compared to those treated with prior-TKIs-only and sequential-TKI-osi. Whereas, 1L osi was inferior to both txs in OS for ex19del pts. This finding may be unique and significant in Asian ex19del pts, though our analysis is limited by the small cohort of a retrospective study. Larger cohorts from retrospective studies or prospective trials are needed to investigate the response of Asian ex19del pts to 1L osi, while underling the need for novel tx options for L858R pts.

Concurrent enhancer of Zeste homolog 2 (EZH2) over-expression with BRAFV600E mutation predicts a poor outcome in patients with Langerhans cell histiocytosis (LCH): A pilot study.

e18536 Background: Prior studies demonstrated upregulated EZH2 protein expression and p-ERK1/2 cascade signaling in histiocytic and dendritic cell neoplasms. BRAFV600E is the most common driver mutation reported in LCH patients (34-64%). In melanoma studies, a signaling pathway with BRAFV600E activating mutation resulted in upregulation of EZH2. The frequency of EZH2 co-expression with BRAFV600E is unknown in LCH. Given the limited durable responses after discontinuation of treatment with BRAF inhibitors in histiocytic disorders, we investigated the prognostic role of EZH2 overexpression and BRAFV600E mutation in LCH. Methods: We analyzed a cohort of 27 consecutive patients (pts) diagnosed with LCH at Moffitt Cancer Center and Tampa General Hospital between 2010-2022. Immunohistochemical (IHC) staining using antibodies against EZH2 (D2C9 clone, Cell Signaling) and BRAFV600E (VE1 clone, Ventana medical systems) were performed. Expression was assessed by an IHC score of stain intensity (0, 1+, 2+ and 3+) multiplied by percent positive cells (H score). H score ≥ 30 was considered as positive. Pyrosequencing was performed to detect BRAFV600E mutations and correlated with VE1 staining results. A positive outcome from either IHC or PCR was deemed indicative of mutation positivity, given the robust presence of mutation representation in melanoma studies through IHC. Results: Entire cohort were grouped for pts who had both EZH2 overexpression and BRAFV600E mutation (EZH2/BRAFV600E) versus those who did not. Out of 27 pts, 25.9% (n=7) had both EZH2/BRAFV600E. EZH2/BRAFV600E group differed from control group by age ( p=0.046). BRAFV600E mutation was identified in 37.03% (10) pts, and 40.7% (11) showed expression of VE1 by IHC study. Discrepancies between PCR and IHC study were observed in 4 pts and potentially attributable to the restricted availability of tissue samples. 63% and 48.1% of pts were positive for EZH2 and BRAFV600E respectively. 6 pts were observed, 8 underwent surgery with or without radiation, 12 received induction chemotherapy, and only 1 received a BRAF inhibitor. After 18.6 months of median follow up, 92.6% pts were alive. Overall response rate (ORR) to the 1st line therapy was 55.6%. In univariate analysis of OS, H score and BRAFV600E mutation trended towards worse OS but were not statistically significant owing to small sample size. However, BRAFV600E mutation and EZH2 over expression demonstrated a poor overall survival (OS) ( p=0.012). Conclusions: Our study indicates that concurrent presence of BRAFV600E mutation and EZH2 overexpression correlates with poor OS in LCH pts. We hypothesize that in a subset of LCH pts combination therapy targeting both EZH2 and BRAFV600E may improve ORR or overcome resistance to BRAF inhibitor monotherapy. However, the results of our pilot study need to be validated on a larger sample set.

Characterization of complete responders to nivolumab + gemcitabine-cisplatin vs gemcitabine-cisplatin alone and patients with lymph node–only metastatic urothelial carcinoma from the CheckMate 901 trial.

4509 Background: In the CheckMate 901 trial, combination nivolumab (NIVO) + gemcitabine-cisplatin (GC) demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) with compelling objective response rates (ORR; 57.6% with NIVO+GC vs 43.1% with GC alone) and deep, durable complete responses (CR; 21.7% with NIVO+GC vs 11.8% with GC alone) in patients (pts) with previously untreated unresectable or metastatic urothelial carcinoma (mUC). Lymph node (LN)-only metastatic disease is a favorable prognostic factor in pts with mUC and a subset of pts achieve durable disease-free, treatment-free survival with GC +/- surgical consolidation. We conducted a post hoc analysis to characterize the subset of pts with CR, with further analysis of pts with LN-only mUC. Methods: In the global, open-label, randomized, phase 3 CheckMate 901 (NCT03036098) trial, cisplatin-eligible pts received NIVO 360 mg + GC every 3 wk for ≤6 cycles followed by NIVO 480 mg every 4 wk until disease progression/unacceptable toxicity or up to a maximum of 2 yrs, or GC every 3 wk for ≤6 cycles. Primary endpoints were OS and PFS by blinded independent central review (BICR). ORR per BICR and safety were exploratory endpoints. These post hoc analyses evaluated treatment outcomes in complete responders and in pts with LN-only disease. Results: Of the 608 pts randomized, 102 (16.8%) achieved a CR. Baseline disease characteristics of these pts are shown in the Table. As pts with LN-only mUC were enriched in the CR group, additional analysis of this subgroup was performed. Of all randomized pts, 54 treated with NIVO+GC and 56 treated with GC had LN-only mUC. In these pts, the ORR and CR rate was 81.5% (95% CI 68.6-90.7) and 63.0% versus 64.3% (50.4-76.6%) and 33.9% for NIVO+GC and GC, respectively. Median OS (95% CI) in LN-only pts was 46.3 (24.0-NE) mos with NIVO+GC vs 24.9 (21.4-29.9) with GC (HR, 0.58, 95% CI 0.34-1.00), and median PFS (95% CI) was 30.5 (9.6-NE) mos with NIVO+GC vs 8.8 (7.5-10.9) mos with GC (HR 0.38, 95% CI 0.22-0.66). Conclusions: NIVO+GC generated deep responses in CheckMate 901 with a fixed duration of chemotherapy and up to 2 years NIVO. Exploratory characterization of pts with CR identified a group of pts enriched with LN-only disease.In pts with LN-only mUC, NIVO+GC induced durable disease control and clinically meaningful improvements in OS and PFS vs GC alone. These results provide additional support for NIVO plus cisplatin-based chemo as a first-line treatment option for pts with mUC. Clinical trial information: NCT03036098 . [Table: see text]

Abstract PO3-03-04: Metaplastic breast cancer: a single center retrospective study

Abstract Background: Metaplastic breast cancer (MBC) is a rare malignancy that accounts for up to 1% of all primary invasive breast carcinomas (BC). It is histologically heterogeneous, usually presents with a triple-negative phenotype and comprises low-grade and high-grade (HG) variants. HG variants have a higher risk of recurrence and a shorter disease-free and overall survival compared to other BC subtypes. Our research aimed to estimate the prevalence of HG-MBC among the Slovenian population and determine the characteristics of patients (pts) and tumours and the disease outcome. Patients and methods: Our retrospective study included pts diagnosed with HG-MBC at the Institute of Oncology Ljubljana from January 1983 until January 2021. Clinicopathologic characteristics such as tumour subtype, size and grade, nodal status, hormonal receptors (HR) and HER-2 status, lymphovascular invasion (LVI), tumour-infiltrating lymphocytes (TIL) and presence of germline BRCA mutation status were determined. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model examined the association between risk factors and survival outcomes. Results: We evaluated 113 HG-MBC pts among a total of 27700 pts diagnosed with BC over 38 years (0.41%). The median age was 61.6 years (range 29.7 -93.9), majority of pts were postmenopausal (78.69%). The median follow-up was 15.5 years. The most common tumour subtype in our cohort was mixed MBC (53 cases, 46.9%), followed by MBC with mesenchymal differentiation (24 cases, 21.2%), squamous cell carcinoma (20 cases, 17.7%) and spindle cell carcinoma (16 cases, 14.2%). From the 113 evaluated pts, we obtained data about the stage in 105 pts, pathological tumour size in 100 pts, number of positive lymph nodes in 99 pts, HR status in 95 pts, HER2 status in 76 pts, grade in 97 pts, LVI in 85 pts, MIB-1 in 41 pts and TIL in 77 pts. At diagnosis, 17/105 pts (16.2%) had stage I disease, 59/105 pts (56.2%) stage II, 25/105 pts (23.8%) stage III and 4/105 pts (3,8%) stage IV. Most tumours were poorly differentiated (90/97, 92.2%) without LVI (60/85, 70.6%). Only 6/95 (6,3%) pts had positive HR, 7/76 (9.2%) pts had positive HER-2 status and 8/77(10.4%) pts intensive TIL. Overall, 13 pts were tested for BRCA germline mutation, among which only 1 (7,7%) had BRCA1 mutation. Modified radical mastectomy was the most frequent type of surgery (63.5%); 49.5% of the patients received radiotherapy. In total, 66/113 pts received CT: from 1983 to 2000, 16/36 (44.4%), and after 2000 50/77 (74.9%). In the first period, most pts received CMF (14/16; 87.5%) and anthracyclines and taxanes (27/50; 54%) in the second period. The disease progressed at 37 pts. At 19 pts, new malignancies were found. 55 pts died, 37 of them because of BC. Five- and 10-year disease-free survival (DFS) was 61.7% and 54.1%, while 5-and 10-year overall survival (OS) was 67.1 % and 56.7%, respectively. However, DFS and OS did not differ between the pre-2000 and post-2000 periods. The best outcome was found in pts with squamous cell carcinoma (5- and 10-year DFS 83.5% and 77.0% and 5-and 10- year OS 89.4 % and 83.0%). A subtype of MBC (squamous cell vs other) was the only predictive factor in multivariate analysis for both DFS (HR 0.21; 95% CI 0.05-0.92; p = 0.038 and OS (HR 0.27; 95%CI 0.09-0.78; p = 0.016), no association was seen between survival and tumour size, nodal status, stage, HR and HER2 status, grade, LVI and TILs. Visceral organs were the most common localization of distant metastases (21/37, 56.8%). Metastases in CNS occurred in 9/37 (24.3%) pts. Median OS after the first progression was only 0.9 years. Conclusions: The proportion of HG-MBC in our cohort of pts is 0.41%. Disease outcomes are poor; the 10-year OS of pts with early HG-MBC is only 56.6% and has not improved during the last decades. Squamous cell differentiation predicts a better outcome and is the only independent predictive factor of DFS and OS among HG-MBC pts. Citation Format: Maša Auprih, Gorana Gasljevic, Eva Setina, Anja Zizek, Simona Borstnar. Metaplastic breast cancer: a single center retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-04.

Abstract PO4-04-05: HER2 immunohistochemistry (IHC) expression in HER2-positive (HER2-pos) metastatic breast cancer (mBC): clinical and prognostic differences between IHC 2+ and IHC 3+ populations

Abstract Background: The exploration of heterogeneity in mBC has gained significant interest in optimizing therapeutic strategies. While the impact of differential HER2 IHC staining has been extensively studied in HER2-low neoplasms, limited data is available regarding IHC 2+ and IHC 3+ categories in HER2-pos mBC. The aim of our study is to compare, the clinical variables, metastatic patterns, and prognosis between patients classified as IHC 2+ and IHC 3+ in HER2-pos mBC. Methods: Pts with HER2 pos mBC, determined by HER2 IHC staining of 3+ or 2+ with amplification at the in situ hybridization assay, were selected from the GIM14 study database for analysis. Associations among variables were assessed by conducting logistic regression analyses. Additionally, prognostic factors for overall survival (OS) and time to treatment failure (TTF) were evaluated using both uni- and multi-variable Cox regression models. Results: A total of 766 HER2-pos mBC pts were included in the analysis. Among them, 302 (39%) had IHC score of 2+ and 464 (61%) had a IHC score of 3+. Central nervous system (CSN) metastases (mts) were observed in 68 (9%) pts (32% IHC 2+; 68% IHC 3+), lymph node (LN) mts in 330 (43%) pts (46% IHC 2+; 54% IHC 3+), lung (LU) mts in 182 (24%) pts (46% IHC 2+; 54% IHC 3+), liver (LI) mts in 227 (30%) pts (45% IHC 2+, 55% IHC 3+), skin (SK) mts in 68 (9%) pts (28% IHC 2+; 72% IHC 3+) and pleural (PL) mts in 40 (5%) pts (47% IHC 2+, 53% IHC 3+). In univariable (uni) analysis, IHC 3+ compared to IHC 2+ was significantly associated with SK mts (OR 1.76, P=0.043) and less likely to be associated with LI (OR 0.71, P=0.031), LU (OR 0.70, P =0.036), and LN (OR 0.63, P=0.002) mts. In multivariable (multi) analysis, LN mts maintained statistical significance (OR 0.62, P=0.004). In subgroup analysis, among IHC 3+ patients, factors associated with worse OS pts were neo Tx (HR 1.55, P=0.032), adjuvant radiotherapy (HR 1.34, P=0.042), neo ChT (HR 1.63, P=0.002), CNS mts (HR 1.98, P=0.002), and LI mts (HR 1.68, P< 0.0001). In multi analysis, CNS mts (HR 1.73, P=0.028) and LI mts (HR 1.47, P=0.017) remained prognostic for IHC 3+ subgroup. The only factor associated with worse OS in IHC 2+ pts was LI mts (HR 1.67, P=0.005). Multi analysis in the overall HER2-pos population identified neo chemotherapy (ChT) (HR 1.49, P=0.009), CNS mts (HR 1.53, P=0.003) and PL mts (HR 1.50, P=0.036) as negative prognostic factors for OS, while PL mts (HR 1.74, P=0.048) were associated with a shorter time to treatment failure (TTF). Conclusions: Our exploratory data revealed that HER2-pos mBC with a IHC score of 3+ is less likely to be associated with LN mts and with visceral mts. The site of mts has prognostic significance, as CNS mts are associated with worse OS in pts with an IHC score of 3+ pts, while LI mts are associated with worse OS in both IHC 2+ and 3+ subgroups. However, the IHC score itself (2+ or 3+) does not have independent prognostic value. The relationship between HER2 IHC staining and treatment outcomes requires further investigation to better understand its potential impact on clinical practice. Citation Format: Arianna Dri, Eva Blondeaux, Claudia Bighin, Simona Gasparro, Stefania Russo, Lorenzo Foffano, Palma Pugliese, Andrea Fontana, Enrico Cortesi, Antonella Ferzi, Ferdinando Riccardi, Valentina Sini, Luca Boni, Alessandra Fabi, Filippo Montemurro, Michelino De Laurentiis, Grazia Arpino, Lucia Del Mastro, Lorenzo Gerratana, Fabio Puglisi. HER2 immunohistochemistry (IHC) expression in HER2-positive (HER2-pos) metastatic breast cancer (mBC): clinical and prognostic differences between IHC 2+ and IHC 3+ populations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-05.

Abstract PO5-06-08: Real-world analysis of efficacy, adverse events and predictive biomarkers for advanced triple negative breast cancer (TNBC) treated with immune check point Inhibitors (ICI): A single center experience

Abstract Introduction KEYNOTE-355 investigated the addition of pembrolizumab to chemotherapy in advanced TNBC patients (pts) with PD-L1 positive tumors showing median overall survival (OS) of 23.0 months (mos) and median progression-free survival (PFS) of 16.1 mos. Given significant OS benefit with pembrolizumab, it is the current standard of care while the indication of atezolizumab has been withdrawn due to lack of OS benefit in IMPASSION-130. Clinical efficacy and adverse events in pts on this treatment regimen in clinical practice is unknown and understanding the real-world outcomes of this regimen is critical. Methods We conducted a retrospective, single-center observational study among TNBC pts treated with ICI (Pembrolizumab or Atezolizumab) at Roswell Park Comprehensive Cancer Center from January 2017 to May 2023. Demographics and clinicopathological variables were collected including comorbidities, laboratory data, sites of metastases (mets), treatment received, immune related adverse events (irAEs), and clinical outcomes. Adverse events were reported using the Common Terminology Criteria for Adverse Events v5.0. Serial CT scans were reviewed and response rate was determined using RECIST v1.1. Patient demographic, clinical and outcome characteristics were summarized by treatment and survival outcomes were obtained using standard Kaplan-Meier methods. Associations between survival outcomes and baseline or treatment characteristics were evaluated using Cox regression models using Firth’s method. All analyses were conducted in SAS v9.4 at a significance level of 0.05. Results A total of 44 pts with advanced TNBC treated with ICI were included (23 received pembrolizumab and 21 received Atezolizumab). The study population consisted of all female pts with stage IV disease, median age 53.7 years (IQR 30.4-85.2), 68.2 % (30/44) White, 25.0% (11/44) Black, 34.1% (15/44) obese (BMI≥30). 27.3% (12/44) pts developed any grade irAEs which included myocarditis (4.5%), rash (9.1%), hyperthyroidism (6.8%), hypothyroidism (4.5%), adrenal insufficiency (2.3%), diabetes mellitus (2.4%), colitis (2.3%), and transaminitis (2.3%). Distribution of reported irAE was 25% grade 1 (3/12), 66.7% grade 2 (8/12) and 8.3% grade 3 (1/12). 75% pts (33/44) received standard treatment (ICI+ chemotherapy) of which 72.7 % (24/33) received it in the first-line setting. Median OS in pts treated in first line was 16.2 mos (95% CI, 10.7-NR) and median PFS was 4.4 mos (95% CI, 2.7-8.4). Overall response rate (ORR) was 29.1% (7/24) of which 8.3% (2/24) had complete response and 20.8% (5/24) had partial response. ORR was 22.2 % (2/9) in pembrolizumab cohort and 33.3 % (5/15) in atezolizumab cohort. Among pts with first line treatment, obese pts were found to have improved PFS compared to non-obese (11.5 vs 3.8 mos, univariate hazard ratio (HR) 0.46, 95% CI 0.23-0.93, p= 0.031), and this difference was maintained in multivariable analysis even after adjusting for age (adjusted HR (aHR) 0.40, 95% CI 0.17-0.98, p= 0.044). Pts with brain mets had poor extracranial PFS compared to those without brain mets (2.8 vs. 5.2 mos, HR 2.25, 95% CI 1.08-4.68, p= 0.036), however this difference was not observed when further adjusted for age (aHR 2.27, 95% CI= 0.91-5.68, p= 0.08). Conclusion Clinical outcomes in our study were inferior to KEYNOTE-355 where median PFS was 16.1 mos and OS was 23.0 mos and ORR was 52.7% for PD-L1 positive population. This may reflect a more heterogeneous population of pts treated in routine clinical practice who are typically less fit than pts on clinical trials. Our study found improved outcomes among obese patients, similar to data reported in other disease settings. These data warrant multi-center validation with larger number of patients. Citation Format: Archit Patel, Arya Mariam Roy, Malak Alharbi, Kristopher Attwood, Chi-Chen Hong, Song Yao, Thaer Khoury, Amy Early, Tracey O'Connor, Ellis Levine, Shipra Gandhi. Real-world analysis of efficacy, adverse events and predictive biomarkers for advanced triple negative breast cancer (TNBC) treated with immune check point Inhibitors (ICI): A single center experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-08.

Abstract PO3-03-05: Clinical outcomes in early-stage TNBC according to HER2-low status

Abstract Background: Clinical outcomes according to HER2 immunohistochemistry (IHC) in patients with early-stage HER2-negative breast cancer have differed across studies. For early-stage TNBC (eTNBC), less representation of this subtype in cohorts studied to date has limited interpretation of results. We sought to evaluate outcomes according to HER2 IHC in a multi-institutional cohort of patients (pts) with eTNBC who received neoadjuvant therapy (NAT). Methods: Pts diagnosed with stage I-III TNBC (including HR-low; ER and PR < 10%) who received NAT and underwent surgery between 1/1/16-6/30/19 were identified across three institutional prospective databases. HER2 was defined as low (1+ or 2+/ISH non-amplified) or HER2-0 according to local testing at diagnosis. Pathological complete response (pCR) was defined as no residual invasive disease in breast and axilla. Multivariable logistic regression was used to compare pCR rates (HER2-low vs HER2-0) adjusting for age at diagnosis, race, anatomic clinical stage, germline BRCA1/2 (gBRCA), histology, HR status and receipt of anthracycline and taxane NAT. Recurrence-free (RFS), distant recurrence-free (DRFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards model was used to estimate adjusted hazard ratios. Results: A total of 978 pts were identified of which 388 (39.7%) had HER2-low and 590 (60.3%) had HER2-0 tumors at diagnosis. Median age was 50.3 (range: 21.0-83.4) yrs. 174 (17.8%) pts had HR-low tumors. 142 (14.5%) pts had a known gBRCA mutation. 790 pts (80.8%) received anthracycline- and taxane NAT. No significant differences were observed in age, race, gBRCA, histology, HR status (low vs negative), clinical tumor size, or type of NAT between HER2-low and HER2-0 groups. Clinical nodal positivity was higher in HER2-low (55.2%) vs HER2-0 (46.6%), p=0.011. No significant difference in pCR was observed between HER2-low (32.0%) and HER2-0 (32.7%) groups, adjusted p=0.928. Among pts with residual disease (RD) post-NAT with HER2 IHC also available in the RD sample, 244/363 (67.2%) had concordant HER2 status. 70/225 (31.1%) of HER2-0 tumors at diagnosis had IHC expression post-NAT (66 HER2-low, 4 HER2-positive); 48/138 (34.8%) of HER2-low tumors at diagnosis were HER2-0 post-NAT. At a median follow-up of 3.1 yrs, RFS did not significantly differ between HER2-low vs HER2-0 pts with pCR (p=0.368) or in those with RD post-NAT (p=0.573). Similarly, DRFS did not differ according to HER2 category for pts with pCR (p=0.509) or RD (p=0.812), nor did OS for pts with pCR (p=0.514) or RD (p=0.285) (Table 1). Conclusion: In a large cohort of pts with eTNBC treated with NAT, HER2-low status was not associated with pCR or survival after adjusting for clinical factors. High rate of discordance in HER2 IHC between diagnostic and RD post-NAT was observed, highlighting the importance of repeat IHC testing in serial samples given the development of antibody drug conjugates for HER2-low breast cancer. Table 1. RFS, DRFS and OS by HER2 expression Citation Format: Ana Garrido-Castro, Danielle Brandes Zakon, Qingchun Jin, Michael Grimm, Akshara Singareeka Raghavendra, Melissa Hughes, Mathew Cherian, Julie Vincuilla, Tonia Parker, Paolo Tarantino, Elizabeth Mittendorf, Tari King, Vicente Valero, Debu Tripathy, Bhuvaneswari Ramaswamy, Sara Tolaney, Nabihah Tayob, Nancy Lin, Daniel Stover, Carlos Barcenas. Clinical outcomes in early-stage TNBC according to HER2-low status [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-05.