Difference In Median Progression-free Survival Research Articles

A real-world study of TACE combined with regorafenib as a second-line treatment for advanced hepatocellular carcinoma.

e16144 Background: Regorafenib is a guideline-recommended second-line systemic drug, and its combination with transarterial chemoembolization (TACE) for the treatment of advanced liver cancer after first-line therapy has been gradually recognized by clinicians. We investigated the efficacy and safety of TACE combined with regorafenib with or without anti-PD-1 immunotherapy as a second line choice for advanced hepatocellular carcinoma (HCC). Methods: In this retrospective study, we retrieved patients with advanced liver cancer who had failed first-line therapy in our center from January 2019 to December 2021, and screened out patients who received TACE combined with regorafenib as second-line therapy. The data of objective response rate (ORR), progression-free survival (PFS) and adverse reactions (ARs) of treatment in these patients were analyzed and summarized. Subgroup analysis of patients with and without PD-1 inhibitors was also performed. Results: A total of 43 eligible patients were screened and treated with TACE in combination with regorafenib in second-line therapy, including 29 patients treated with PD-1 inhibitors. In all patients, one patient had complete response (CR) and 11 patients had partial response (PR), with ORR of 27.91% (12/43) and 24 patients had stable disease (SD), with disease control rate (DCR) of 83.72% (36/43). The median PFS was 10.0 months for all patients in survival follow-up, with PFS rates of 77.65% and 37.17% at 6 and 12 months follow-ups, respectively. Overall survival (OS) rates were 90.49%, 67.03%, and 58.65% at 12, 18, and 24 months, respectively. In subgroup analysis, there was no statistical difference in median PFS between the groups with or without PD-1 inhibitors (11.0 months vs 8.0 months, p=0.229), but there was a trend toward survival benefit in the combined group (hazard ratio/HR 0.62). The incidence of treatment-related ARs in all treated patients was 81.40% (35/43), all grade 1-2. Among ARs, hand-foot syndrome (27.91%), loss of appetite (20.93%), and elevated transaminases (16.28%) were predominant. Conclusions: This study verified the efficacy and safety of TACE combined with regorafenib as second-line therapy for the treatment of advanced HCC after failure of first-line therapy, and the results need to be further justified in future prospective studies with larger sample sizes. [Table: see text]

Impact of synchronous (sync) vs metachronous (meta) metastasis at the presentation on survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor signaling inhibitors (ARSIs).

5049 Background: Pts with sync metastatic castration-sensitive prostate cancer (mCSPC) appear to have worse survival outcomes and earlier time to developing castration resistance than pts with meta mCSPC (PMID: 33914595). However, the impact of the initial timing of metastasis on survival in the mCRPC setting is less clear. Herein, our objective was to assess the correlation between the sync/meta metastatic disease presentation and survival in real-world newly diagnosed mCRPC pts. Methods: In this IRB-approved study, patient-level data were collected retrospectively. Eligibility: confirmed diagnosis of mCRPC, treatment with ARSI (abiraterone or enzalutamide) as first-line (1L) therapy for mCRPC, and no prior exposure to ARSI in the mCSPC or localized states. The disease was considered sync if distant metastasis was diagnosed within 90 days of the initial prostate cancer diagnosis. Study endpoints: progression-free survival (PFS) was defined from the start of therapy for 1L mCRPC to progression (per PCWG-2) or death from any cause. Overall survival (OS) was defined from the start of therapy for 1L mCRPC to the date of death from any cause or censored at the last follow-up. A multivariate analysis using the Cox proportional hazards model was used, adjusting for potential confounders. Results: 323 pts (144 sync and 179 meta) were eligible and included in the analysis. Sync and meta pts had respectively similar baseline characteristics: median PSA (19.6 vs 20.8 ng/ml), liver metastasis (9 vs 12.3%), median alkaline phosphatase (97 vs 95 IU/L), and ECOG performance > 1 (9 vs 3.9%). The difference in median PFS was not statistically significant (8.2 vs. 10.7 months, HR 1.13, 95% CI 0.85-1.49, p=0.4 for sync and meta, respectively). Median OS was significantly shorter in pts with sync compared to meta (26 vs. 38.7 months, HR 1.51, 95% CI 1.11-2.08, p=0.01). In the multivariate analysis, the initial timing of metastasis remained an independent prognostic factor. Conclusions: For the first time, we report the impact of the initial timing of metastasis on mCRPC prognosis in a real-world patient population with sync disease being associated with having a poor prognosis. Initial timing of metastasis may be worth accounting for in future mCRPC clinical trials to explore its prognostic value further. These hypothesis-generating data need external validation. [Table: see text]

Validation of the PDACai signature in predicting relative benefit from frontline FOLFIRINOX (FFX) and gemcitabine/nab-paclitaxel (GA) for patients (pts) with metastatic pancreatic cancer (mPDAC).

4149 Background: Nearly 50% of pts with mPDAC never receive a 2nd line of therapy for metastatic disease following frontline FFX or GA. Genomic alterations in the DDR pathway (e.g. BRCA1/2) are associated with increased progression-free survival (PFS) on platinum-containing regimens (e.g. FFX), but other biomarker-treatment associations that predict benefit from GA and/or FFX in mPDAC remain unexplored. In this retrospective real-world evidence (RWE) study, we use a data-driven machine learning approach to gain new insights from the mutational landscape in mPDAC and validate the PDACai signature in predicting personalized benefit from both FFX and GA. Methods: We analyzed real-world outcomes from 711 pts with mPDAC who underwent genomic profiling via the Know Your Tumor program or were referred to Perthera by treating oncologists. Chart-abstracted PFS data on either 1st line FFX or GA were split (60:40) into independent training and validation cohorts for each regimen. All models integrate a shared set of clinical (age < 63, sex) and lab-agnostic molecular features derived from clinical NGS testing reports (DDR pathway alterations, specific KRAS variants, frequently mutated genes). Relative benefit scores predicted by FFX or GA models were evenly binned into three PDACai signature categories representing lower, middle, and upper tertiles for each independent cohort. Statistical differences in median PFS were evaluated using ordinal Cox regression. Results: Median PFS followed predicted trends as generated by PDACai for each therapy in training and validation cohorts. The predictive utility of PDACai was confirmed in the independent validation cohorts when comparing PFS on FFX (p = 0.03744; HR = 0.75 [95% CI: 0.58-0.98]) and GA (p = 0.00006861; HR = 0.65 [95% CI: 0.53-0.8]) across tertiles. Conclusions: Response to chemotherapy is heterogeneous and difficult to predict in pts with mPDAC. Using RWE, the PDACai signature successfully predicted relative differences in PFS on both FFX and GA in mPDAC. With prospective validation, personalized insights generated by PDACai from pts with similar biomarker profiles could be used to tailor treatment sequencing in pts with NGS testing results, particularly those without actionable genomic findings. [Table: see text]

Differential efficacy of tyrosine kinase inhibitors (TKIs) according to the types of EGFR mutations and agents in non-small cell lung cancer (NSCLC): A real-world study.

e21040 Background: Both 1st and 2nd-generation (gen) EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data about the difference in the efficacy of EGFR-TKIs according to types of EGFR mutations and agents. Methods: This retrospective real-world study evaluated the outcome and clinicopathologic characteristics including the type of EGFR mutations in 237 advanced NSCLC patients (pts) treated with 1st or 2nd-gen (afatinib) EGFR TKIs as first-line therapy. Results: The median progression-free survival (PFS) and overall-survival (OS) of all pts were 11 months (M) and 25M, respectively. In univariate analysis, pts with exon 19 deletion (del) (n = 130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p = 0.047), without difference in PFS (p = 0.138). Pts treated with afatinib (n = 60) showed significant longer median OS compared to those treated with 1st gen TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p = 0.037). In pts with exon 19 del, there was no significant difference in median PFS (p = 0.868) and OS (p = 0.361) between pts treated with afatinib and those with 1st gen TKIs, while significantly better PFS (p = 0.042) and trend in OS (p = 0.069) were observed in pts receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p = 0.028), while age > 70 years (p = 0.017), ECOG performance status ≥2 (p = 0.001), primary metastatic disease (p = 0.007), and synchronous brain metastasis (p = 0.0026) were independent prognostic factors of poor OS. Conclusions: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC pts receiving first-line EGFR TKIs. Moreover, in pts with exon 19 del, first generation TKIs seem to be a reasonable option if osimertinib is unavailable.

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma.

Daratumumab is an anti-CD38 mAb, used frequently in combination with lenalidomide and pomalidomide. No studies compared daratumumab plus lenalidomide and dexamethasone (DRd) to daratumumab plus pomalidomide and dexamethasone (DPd) in lenalidomide-exposed multiple myeloma. We identified 504 consecutive multiple myeloma patients who received daratumumab at Mayo Clinic between January 2015 and April 2019. We excluded patients who received daratumumab in the first line, received more than four lines of therapy prior to daratumumab use, did not receive lenalidomide prior to daratumumab, or had an unknown status of lenalidomide exposure, and patients who received daratumumab combinations other than DRd or DPd. We examined the impact of using DRd compared to DPd on progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory multiple myeloma. Out of 504 patients, 162 received DRd or DPd and were included; 67 were lenalidomide-exposed and 95 were lenalidomide-refractory. DRd was used in 76 (47%) and DPd in 86 (53%) patients. In lenalidomide-exposed multiple myeloma, there was no difference in median PFS; 34.2 months [95% confidence interval (CI), 22.8-44.6] for DRd compared to 25.2 months (95% CI, 4.9-35.3) for DPd, P = 0.2. In lenalidomide-refractory multiple myeloma, there was no difference in median PFS; 18.6 months (95% CI, 13-32) for DRd compared to 9 months (95% CI, 5.2-14.6) for DPd, P = 0.09. No difference in median OS was observed in DRd compared to DPd. Our study shows combining daratumumab with lenalidomide in patients with prior lenalidomide use is a viable and effective treatment option.

Abstract P4-01-43: PyrotInib in combination with Capecitabine for trasTUzumab-REsistant, HER2-positive advanced breast cancer (PICTURE): a multicenter phase 2 trial

Abstract Background: Approximately 10% of patients with HER2-positive breast cancer have primary resistance to trastuzumab, leading to poor prognosis. Although several trials enrolled those hard-to-treat patients, there has been no strong evidence available for the clinical decision making. This multicenter phase 2 trial aimed to investigate the activity and safety of pyrotinib plus capecitabine only in those patients with trastuzumab-resistant, HER2-positive advanced breast cancer. Methods: Patients from 17 sites in China received pyrotinib 400 mg once a day and capecitabine 1000 mg/m2 twice a day on days 1-14 every 21 days until disease progression or intolerable toxicity. Based on the definitions used in prior clinical trials, primary trastuzumab resistance was defined as progression during trastuzumab treatment (Group 1) or within 12 months after completing trastuzumab treatment in the (neo)adjuvant setting (trastzuzumab should have been for ≥9 weeks, Group 2), or progression within 6 months after the initiation of trastuzumab treatment in the advanced setting (treatment should have been for ≥6 weeks, Group 3). The primary endpoint was progression-free survival (PFS). The study is registered with ClinicalTrials.gov, NCT04001621. Results: Between June 2019 and September 2021, a total of 100 patients enrolled; 35 (35.0%) patients had hormone receptor (HR)-positive disease, and 65 (65.0%) had HR-negative disease. Prior use of trastuzumab, pertuzumab and antibody-drug conjugate was reported in 100%, 21.0% and 2.0% of patients, respectively. By the data cutoff on July 10, 2022, the median follow-up duration was 23.4 months (95%CI, 20.5-25.6) with 66 PFS events documented. Median PFS was 11.8 months (95%CI, 8.4-15.1) in the overall population. Patients in Group 2 (n=49) had the longest median PFS of 17.8 months (95%CI, 13.8-not reached), which was significantly different from either 8.2 months (95%CI, 3.0-20.7; p = 0.001) in Group 1 (n=21) or 5.6 months (95%CI, 4.1-6.9; p < 0.001) in Group 3 (n=30). No significant difference in median PFS was observed in subgroup by HR status (HR-positive: 9.7 months [95%CI, 6.4-18.4]; HR-negative: 12.3 months [95%CI, 8.2-17.8]; p = 0.764). Objective response rate was 70.0% (95%CI, 60.0%-78.8%). Overall survival data was immature. The most common grade ≥3 treatment-emergent adverse events included diarrhea (24.0%), palmar-plantar erythrodysaesthesia syndrome (9.0%), neutrophil count decreased (7.0%), hypokalemia (5.0%), and decreased appetite (5.0%). No treatment-related deaths occurred. Conclusions: Pyrotinib plus capecitabine resulted in a promising PFS that crossed the pre-specified efficacy boundary in patients with HER2-positive advanced breast cancer who met the traditional definition of primary trastuzumab resistance. Patients in Group 2 had a significant longer PFS than those in either Group 1 or Group 3, highlighting the need to re-define primary trastuzumab resistance and to clarify efficacy of new anti-HER2 biologicals for each subpopulation. Citation Format: Xichun Hu, Jun Cao, Yue’e Teng, Hui-Ping Li, Lili Zhang, Quchang Ouyang, Weimin Xie, Yueyin Pan, Zhenchuan Song, Xiaoling Ling, Xiaohong Wu, Jingwei Xu, Li Li, Liping Ren, Hong Wang, Dongxian Zhou, Jing Luo. PyrotInib in combination with Capecitabine for trasTUzumab-REsistant, HER2-positive advanced breast cancer (PICTURE): a multicenter phase 2 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-43.

A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma.

Relapsed or refractory classical Hodgkin lymphoma (cHL) remains a difficult treatment challenge. Although checkpoint inhibitors (CPI) have provided clinical benefit for these patients, responses are generally not durable, and progression eventually occurs. Discovering combination therapies which maximize the immune response of CPI therapy may overcome this limitation. We hypothesized that adding ibrutinib to nivolumab will lead to deeper and more durable responses in cHL by promoting a more favorable immune microenvironment leading to enhanced T-cell-mediated anti-lymphoma responses. We conducted a single arm, phase II clinical trial testing the efficacy of nivolumab in combination with ibrutinib in patients ≥18 years of age with histologically confirmed cHL who had received at least one prior line of therapy. Prior treatment with CPIs was allowed. Ibrutinib was administered at 560 mg daily until progression in combination with nivolumab 3 mg/kg IV every 3 weeks for up to 16 cycles. The primary objective was complete response rate (CRR) assessed per Lugano criteria. Secondary objectives included overall response rate (ORR), safety, progression free survival (PFS), and duration of response (DoR). A total of 17 patients from two academic centers were enrolled. The median age of all patients was 40 (range 20-84). The median number of prior lines of treatment was five (range 1-8), including 10 patients (58.8%) who had progressed on prior nivolumab therapy. Most treatment related events were mild (<Grade 3) and expected from the individual side effect profiles of ibrutinib and nivolumab. In the intent to treat population (n = 17), the ORR and CRR were 51.9% (9/17) and 29.4% (5/17), which did not meet the prespecified efficacy endpoint of a CRR of 50%. In patients who received prior nivolumab therapy (n = 10), the ORR and CRR were 50.0% (5/10) and 20.0% (2/10), respectively. At a median follow up of 8.9 months, the median PFS was 17.3 months, and the median DOR was 20.2 months. There was no statistically significant difference in median PFS between patients who received previous nivolumab therapy versus patients who were nivolumab naïve (13.2 months vs. 22.0 months, p = 0.164). Combined nivolumab and ibrutinib led to a CRR of 29.4% in R/R cHL. Although this study did not meet its primary efficacy endpoint of a CRR of 50%, likely due to enrollment of heavily pretreated patients including over half of who had progressed on prior nivolumab treatment, responses that were achieved with combination ibrutinib and nivolumab therapy tended to be durable even in the case of prior progression on nivolumab therapy. Larger studies investigating the efficacy of dual BTK inhibitor/immune checkpoint blockade, particularly in patients who had previously progressed on checkpoint blockade therapy, are warranted.

Prognostic impact of immune-related adverse events on survival outcomes in metastatic gastrointestinal cancer: A single-institutional experience.

801 Background: Immune checkpoint inhibitors (ICIs) have several approved indications in the treatment of gastrointestinal (GI) malignancies including metastatic disease. The adverse events related to ICI use or Immune related adverse events (irAEs) are now being more readily recognized. The association between the occurrence of irAEs and survival outcomes is not well understood. Whereas complete tolerability of ICIs with minimal irAEs may be indicative of a lack of response, the development of moderate to severe irAEs could result in significant morbidity and mortality especially in already advanced disease. This dilemma has provided an impetus to present our 5-year single institutional experience wherein we aim to determine the impact of irAEs on survival outcomes in metastatic GI malignancies. Methods: We retrospectively reviewed a cohort of adult patients who received ICIs for metastatic GI malignancies at the Cleveland Clinic foundation between 2017-2022 by utilizing an outpatient oncology pharmacy database. ICIs of interest included atezolizumab, ipilimumab, nivolumab and pembrolizumab. The occurrence of irAEs was as determined by primary oncologist. The primary and secondary outcomes were overall survival (OS) and progression free survival (PFS) in patients based on irAE presence, respectively. Results: There was a total of 151 patients who received ICIs for various metastatic GI malignancies. Among these, 38 unique irAEs were identified constituting 25% of the entire cohort. The table shows their distribution by organ system and type of GI malignancy. We observed hyper progressive disease in 3% of irAE cohort. Grade 3-4 irAEs requiring hospitalization occurred in 32% of all irAEs, median hospital length of stay of 5 (range:1-15) days with 11% resulting in death. 26 % discontinued treatment due to irAEs while 44% had palliative care consultations/hospice transition soon after. The median OS rates in patients who had irAEs vs those who didn’t, respectively, were 10 months [95% confidence interval (CI, 5-NA)] vs. 9 months [95% confidence interval (CI, 6-12)], p=0.85. There was also no statistically significant difference in median PFS between both groups (p=0.76). Conclusions: In our single institution cohort of metastatic gastrointestinal cancer patients, despite significant morbidity from irAEs, the prognosis was similar as previous studies suggesting a better outcome in patients with irAEs compared to those who did not experience irAEs.[Table: see text]

Efficacy and Prognostic Factors of Regorafenib in the Treatment of BCLC Stage C Hepatocellular Carcinoma After Failure of the First-Line Therapy.

Regorafenib is a standard second-line treatment for hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy and safety of regorafenib in the treatment of patients with Barcelona clinic liver cancer (BCLC) stage C HCC after failure of the first-line therapy and to analyze factors affecting the efficacy of regorafenib as the second-line treatment. A retrospective analysis was conducted on 103 BCLC stage C HCC patients who received regorafenib as the second-line treatment. Among them, 51 patients received regorafenib plus transarterial chemoembolization (TACE) and 52 patients received regorafenib alone. Progression-free survival (PFS), overall survival (OS), and adverse events were compared between the two groups, and factors influencing the efficacy of regorafenib were analyzed. In patients with BCLC stage C HCC after failure of the first-line therapy, there was no statistically significant difference in median PFS between regorafenib plus TACE group and regorafenib group (5.3 vs 4.0 months, P=0.432). The median OS was significantly longer in the regorafenib plus TACE group than that in the regorafenib group (11.3 vs 8.2 months, P=0.034). Patients in both groups experienced adverse events at rates of 78.43% and 75%, respectively. Rates of grade III-IV serious adverse events were 19.61% and 13.46%, respectively. Hand-foot skin reactions, fatigue, abdominal pain, and hypertension were common side effects of regorafenib. The number of tumors was noted as an independent prognostic factor for PFS in the univariate and multivariate Cox regression analyses, while Eastern Cooperative Oncology Group (ECOG) performance status (ECOG-PS) score, tumor size, the number of tumors, and combined local therapy were independent prognostic factors for OS. Regorafenib combined with TACE treatment improved OS for patients with ECOG-PS scores of 0-1, tumor size < 5 cm, and the number of tumors ≥ 3 compared with regorafenib alone. Regorafenib exhibited to be a safe and effective sequential therapy for patients with BCLC stage C HCC after failure of the first-line treatment, and its combination with TACE could achieve a higher efficacy. ECOG-PS score, tumor size, the number of tumors, and combined local therapy were noted as prognostic factors affecting patients with BCLC stage C HCC who were treated with regorafenib.

The Impact of Poorly Differentiated Histology on Immunotherapy in Advanced Gastrointestinal Cancers

Introduction: Checkpoint inhibitors (CPI) have significantly improved survival among patients with various cancer types. Prior studies have shown a correlation between immune cell infiltration and poorly differentiated cancers. This study evaluated the impact of poorly differentiated histology on survival in patients with advanced gastrointestinal cancers treated with immunotherapy. Methods: This study was a retrospective, single-center analysis of patients with gastrointestinal cancers treated with CPIs between 2016 and 2021. Univariate and multivariable analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor and patient characteristics, progression-free survival, and overall survival. Results: A total of 123 patients were eligible and included in the analysis. Median age was 66 years (23–88 years). Majority had stage IV disease (89%), were white (65.5%), and were male (64.5%). Most common diagnoses were hepatocellular carcinoma (30.5%), gastric adenocarcinoma (16.5%), esophageal adenocarcinoma (17%), and colorectal cancer (19.8%). About 32% of the tumors were microsatellite instability-high (MSI-High/dMMR), with BRAF V600E mutation rate of 10%. About 25% of the patients received CPIs as initial treatment, while 35.5% had received two or more prior lines of therapy. Compared with well and moderately differentiated histology, patients with poorly differentiated tumors had a shorter median overall survival (mOS) (not reached [NR] vs. NR vs. 9.3 months, p = 0.0264). There was no statistically significant difference in median progression-free survival (mPFS) between histology types (2.5 vs. 4.2 vs. 2 months, p = 0.1314). On univariate survival analysis, moderately differentiated tumors correlated with a significantly longer mOS (HR: 0.48, CI: 0.24–0.93, p = 0.030) and mPFS (HR: 0.62, 95% CI: 0.38–1.00, p = 0.048) compared to poorly differentiated histology. Female patients (HR: 0.55, 95% CI: 0.34–0.90, p = 0.018) and the Eastern Cooperative Oncology Group (ECOG) of 1 (vs. ≥2) had significantly longer mPFS (HR: 0.58, 95% CI: 0.35–0.97, p = 0.036). ECOG of 1 also correlated with longer mOS (HR: 0.47, 95% CI: 0.23–0.94, p = 0.034). Microsatellite stable (MSS) tumors had significantly shorter mPFS (HR: 5.74, 95% CI: 2.41–13.63, p < 0.001) and mOS (HR: 5.45, 95% CI: 1.64–18.12, p = 0.006). The number of prior systemic therapies was also associated with shorter mPFS (HR: 1.19, 95% CI: 1.03–1.39, p = 0.022) and mOS (HR: 1.23, 95% CI: 1.01–1.50, p = 0.045). On multivariable analyses, ECOG status of 0/1 versus ≥2 and MSI-High/dMMR versus MSS remained significantly associated with longer mPFS and mOS. There was no correlation with histologic differentiation status, race, or mutations such as BRAF V600E or KRAS. Conclusion: Results from this study demonstrate that poorly differentiated histology was associated with shorter mOS but was not associated with improved PFS in patients treated with CPI. Treatment-naïve patients, moderately differentiated tumors, female gender, ECOG 1, and MSI-High/dMMR were most likely to benefit from CPI.

Abstract B127: Impact of race on the outcomes of advanced stage non-small cell lung cancer in an equal access setting

Abstract Introduction: Immunotherapy has improved outcomes in patients with advanced stage lung cancer. However, the studies which led to approval of these therapies did not include a substantial number of Black patients. Studies focusing on racial disparities in advanced stage non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) report conflicting data. In an equal access setting, some studies have demonstrated improved outcomes in Black patients. Very few studies have high or equal representation of Black patients, and these studies lack detail on access to care, such as time to treatment initiation (TTI) in this target population. To our knowledge, this study is one of few with almost equal representation of Black and White patients. Methods: This was an IRB approved retrospective study of stage IV NSCLC patients &amp;gt; 18 years who received immunotherapy-based systemic therapy at Vidant Medical Center between 2014 and 2021. Analyses were done utilizing IBM PSAW (SPSS Version 28). Associations between race and other demographic characteristics were examined using chi-square tests. Kaplan-Meier curves were generated to determine overall survival (OS) and progression-free survival (PFS) stratified by race. Multivariate Cox proportional hazards model was applied to determine predictors of OS and PFS. A p-value &amp;lt; 0.05 was deemed statistically significant. Results: Of 194 patients who met the eligibility criteria, 42.3% were Black (n=82). On Kaplan-Meier analysis, there was no difference in median PFS (6.30 versus 7.90 months; log-rank p=0.977) and OS (9.50 versus 11.77 months; log-rank p=0.457) between White and Black patients respectively. On multivariate analysis, there was no difference in PFS (HR: 0.98; 95% CI: 0.68,1.43; p=0.928) or OS (HR: 1.01; 95% CI: 0.67,1.51; p=0.969) when controlling for race, sex, age at diagnosis, pack years, marital status, insurance type, histology, and Charlson Comorbidity Index (CCI). The most frequently administered ICIs were pembrolizumab (74.7%), nivolumab (13.4%), atezolizumab (8.8%), nivolumab plus ipilimumab (1.5%), and durvalumab (1.5%). There was no difference in treatment selection between Black and White patients (p=0.184; chi-square). Median time to initial overall cancer treatment initiation (28.00 days versus 22.00 days; p=0.159) did not differ, but there was a significant difference in median time to immunotherapy initiation (34.00 versus 27.00 days; p=0.042) between White and Black patients respectively. Conclusion: Although race was expected to permeate patient outcomes, OS and PFS did not differ between Black and White patients. The significantly shorter time to immunotherapy treatment for Black patients is an unexpected finding. In our study we highlighted that equitable access reduces disparities, bridges gaps in care, and improves patient outcomes, regardless of race. Further studies with equitable representation of diverse racial groups are warranted to better understand how race impacts cancer outcomes. Citation Format: Melisa Pasli, Radhamani Kannaiyan, Praveen Namireddy, Mahvish Muzaffar. Impact of race on the outcomes of advanced stage non-small cell lung cancer in an equal access setting [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B127.

Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma.

Telomerase reverse transcriptase promoter (TERTp) mutations are a biological marker of glioblastoma; however, the prognostic significance of TERTp mutational status is controversial. We evaluated this impact by retrospectively analyzing the outcomes of patients with isocitrate dehydrogenase (IDH)- and TERTp-wild-type glioblastomas. Using custom next-generation sequencing, we analyzed 208 glioblastoma samples harboring wild-type IDH. TERTp mutations were detected in 143 samples (68.8%). The remaining 65 (31.2%) were TERTp-wild-type. Among the TERTp-wild-type glioblastoma samples, we observed a significant difference in median progression-free survival (18.6 and 11.4 months, respectively) and overall survival (not reached and 15.7 months, respectively) in patients with and without phosphatase and tensin homolog (PTEN) loss and/or mutation. Patients with TERTp-wild-type glioblastomas with PTEN loss and/or mutation were younger and had higher Karnofsky Performance Status scores than those without PTEN loss and/or mutation. We divided the patients with TERTp-wild-type into 3 clusters using unsupervised hierarchical clustering: Good (PTEN and TP53 alterations; lack of CDKN2A/B homozygous deletion and platelet-derived growth factor receptor alpha (PDGFRA) alterations), intermediate (PTEN alterations, CDKN2A/B homozygous deletion, lack of PDGFRA, and TP53 alterations), and poor (PDGFRA and TP53 alterations, CDKN2A/B homozygous deletion, and lack of PTEN alterations) outcomes. Kaplan-Meier survival analysis indicated that these clusters significantly correlated with the overall survival of TERTp-wild-type glioblastoma patients. Here, we report that PTEN loss and/or mutation is the most useful marker for predicting favorable outcomes in patients with IDH- and TERTp-wild-type glioblastomas. The combination of 4 genes, PTEN, TP53, CDKN2A/B, and PDGFRA, is important for the molecular classification and individual prognosis of patients with IDH- and TERTp-wild-type glioblastomas.

The price, efficacy, and safety of within-class targeted anticancer medicines between domestic and imported drugs in China: a comparative analysis

Affordability to novel anticancer drugs has become a major health issue in China. It is encouraging to note that China initiated its drug regulatory reform and national price negotiation policies since 2015. As a growing number of domestic within-class targeted anticancer drugs are approved in China, it is expected that this may reduce the price of novel anticancer drugs and improve the affordability of anticancer drugs. This study aimed to evaluate the price, efficacy, and safety of the within-class anticancer drugs between domestic and imported drugs approved in China from 2010 to2022. The domestic and imported within-class targeted drugs for solid cancers approved in China between 2010 and 2022 were extracted. We classified it as a class of anticancer drugs based on the same indication and similar biological mechanism. The published literature derived from pivotal clinical trials of these domestic and imported drugs was identified based on the review report and the latest labels issued by the China National Medical Products Administration. We evaluated the monthly treatment price at launch and the latest (2022), primary efficacy endpoint and safety between domestic and imported anticancer drugs. Meta-analyses were further employed to evaluate the efficacy and safety of the domestic and imported anticancer drugs, including pooled hazard ratios (HR) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR) for solid cancers, and relative risk for serious adverse events (SAE) and Grade ≥3 adverse events (AEs). In our cohort study, 12 within-class anticancer drugs with 7 cancer diseases were analyzed, including 18 domestic (21 indications; 21 pivotal trials) and 18 imported (21 indications; 27 pivotal trials) novel anticancer drugs, respectively. The median monthly treatment price of domestic and imported drugs from the years of launch to 2022 had significantly decreased by 71% and 62%, respectively. Moreover, the median monthly treatment price of domestic targeted anticancer drugs on the market at launch ($3786 vs. $5393, P=0.007) and the latest ($1222 vs. $2077, P=0.011) was significantly lower than that of imported drugs. No significant differences in median PFS gains (9.0 vs. 11.0 months; P=0.24), OS gains (9.3 vs 10.6 months; P=0.66), and ORR (57% vs 62%, P=0.77) of targeted anticancer drugs in their pivotal trials were observed between the domestic and imported drugs. Additionally, there was no significant difference between domestic and imported drugs in the incidence of SAE (23% vs. 24%; P=0.41) and Grade ≥3 AEs (59% vs. 57%; P=0.45). These findings were also further confirmed in the meta-analyses for primary efficacy endpoints and safety outcomes. The prices of both domestic and imported anticancer drugs significantly decreased after market entry mainly due to the role of national price negotiations. The median monthly treatment price of domestic within-class targeted anticancer drugs was significantly lower than that of imported drugs. Furthermore, the efficacy and safety of domestic anticancer drugs were comparable to that of imported drugs. This evidence implicated that the development of within-class anticancer drugs with national price negotiations in China significantly improved the affordability for patients. This study was supported by postdoctoral fellowship from Tsinghua-Peking Joint Centers for Life Sciences (CLS).

Efficacy of Osimertinib Combined with Bevacizumab in Advanced Non-small Cell Lung Cancer Patients with Acquired EGFR T790M Mutation

Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) capable of overcoming non-small cell lung cancer (NSCLC) with EGFR T790M mutation. Although the addition of bevacizumab to 1st generation EGFR-TKIs confers a significant improvement in progression-free survival (PFS) in treatment-naive EGFR mutant NSCLC patients, osimertinib plus bevacizumab combination failed to show prolongation in the phase 2 study WJOG8715L. Data of such combination in Chinese patients are still lacking. This study aimed to explore the efficacy of the addition of bevacizumab to osimertinib as second-line therapy in real-world data, and to evaluate the role of anti-angiogenesis plus osimertinib combination therapeutic strategies in pretreated Chinese NSCLC patients with acquired EGFR T790M mutation. A total of 42 advanced NSCLC patients with acquired EGFR T790M mutation after prior EGFR-TKIs treatment were collected between January 2020 to August 2021, with 16 cases treated with osimertinib plus bevacizumab and 26 cases treated with osimertinib. The treatment effect of patients were analyzed. The objective response rate (ORR) in combination group and osimertinib group were 43.8% and 50.0% respectively (P=0.694). No statistically significant difference in median PFS (14.0 mon vs 13.0 mon, P=0.797) and overall survival (OS) (29.0 mon vs 26.0 mon, P=0.544) between the combination group and osimertinib group were observed. Prior history of bevacizumab was identified as an independent predictor of PFS (P=0.045) and OS (P=0.023). Our study demonstrated that adding bevacizumab to osimertinib could not show advantages in PFS and OS in pretreated NSCLC patients harboring EGFR T790M-mutation.

Impact of Circulating Lymphoma at Diagnosis on Outcomes in Patients with Marginal Zone Lymphoma

Introduction Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma that includes 3 subtypes: extranodal marginal zone lymphoma (EMZL) of the mucosa-associated lymphatic tissue (MALT), splenic MZL (SMZL), and nodal MZL (NMZL). Although flow cytometry can detect circulating lymphoma cells in many cases of MZL, outside of case reports and small case series, the relevance of this circulating lymphoma (CL) in patients with MZL at diagnosis is largely unknown. Hence, we sought to evaluate the impact of CL at diagnosis on outcomes in patients with MZL. Methods This multicenter, retrospective cohort study of MZL patients treated at 3 US medical centers included patients who were ≥18 years old, diagnosed with MZL from 2010-2020, and had peripheral blood flow cytometry performed at diagnosis. Patients who never received therapy for MZL were excluded. Patients were classified according to positive or negative flow cytometry results as CL+ and CL-, respectively. The primary endpoint was progression-free survival (PFS) defined as the time from the start of first-line therapy until lymphoma relapse/progression or death from any cause, censoring at the last clinical assessment. Secondary endpoints were overall survival (OS, from the start of first-line therapy until death or last follow-up) and time from diagnosis to systemic therapy in CL+ and CL- groups. Results Among 294 eligible patients with newly diagnosed MZL, 75 (25%) had detectable CL at diagnosis. The CL+ group had a higher median age (66 vs 63 years), advanced-stage disease (100% vs 53%), bone marrow involvement (91% vs 35%), elevated LDH (49% vs 22%), lower albumin (24% vs 13%), and less often received R-chemotherapy (39% vs 41%) compared to the CL- group. SMZL constituted the predominant subtype (52%, n=39) in the CL+ group with NMZL and EMZL constituting 24% each (n=18). The median PFS was not significantly different between the CL+ (6.2 years, 95%CI=3.6-NR) and CL- (5.9 years, 95%CI=4.3-8.4), p=0.73 (Figure 1) groups. Similar results were noted across the MZL subtypes with no significant difference in median PFS in EMZL (p=0.51), NMZL (p=0.51), or SMZL (p=0.38) according to the CL status. The median PFS was not significantly different between CL+ and CL- groups among patients treated with rituximab monotherapy (median PFS 4.1 vs 3.2 years, respectively, p=0.69) or immunochemotherapy (median PFS NR vs 8.7 years, respectively, p=0.84, Figure 2). After adjusting for factors associated with PFS in multivariate cox regression (age, B symptoms, albumin level, LDH>ULN, and type of first-line treatment regimen), there was no difference in PFS between CL+ and CL- groups (HR=0.73, 95%CI=0.45-1.20, p=0.22). We did not observe a significant difference in OS between the CL+ and CL- groups with a 5-year rate of OS being 89% vs 82% in the CL+ and CL- groups (p=0.31). Furthermore, the time from diagnosis to systemic therapy initiation did not significantly differ between the CL+ and CL- groups with % of patients who started treatment at 1, 3, and 5 years from diagnosis being 83% vs 92%, 95% vs 96%, and 97% vs 99%, respectively (p=0.42). Conclusions This is the first study to compare the outcomes of patients with CL+ and CL- groups in newly diagnosed MZL. In this largest study to date evaluating the prognostic relevance of CL in patients with MZL, we found that CL at diagnosis was not associated with shorter PFS, OS, or time from diagnosis to first-line therapy. Further studies should evaluate whether the presence of CL is associated with specific molecular or other clinically relevant markers that were not available in our patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Safety, Feasibility, and Efficacy of Upfront Daratumumab-Based Therapy in Blacks with Dysproteinemia

Background: Black patients (pts) with dysproteinemia are underrepresented in clinical trials included in new drug applications and biological license application submissions. Even after approval, access to novel therapies remains a challenge. Daratumumab (dara) is an anti-CD38 monoclonal antibody, which has revolutionized the care of patients with both multiple myeloma (MM) and light chain (AL) amyloidosis. The underrepresentation of black pts in clinical trials of dara in newly diagnosed patients with dysproteinemia raises concerns regarding the safety, tolerability and efficacy of dara in this population. We report the results from a cohort of pts treated with dara in the management of newly diagnosed MM (NDMM) and AL amyloidosis. Methods: The Cancer and Aging Resilience Evaluation in Hematologic Malignancies (CARE-Heme) registry is an ongoing prospective registry enrolling pts ≥50 years of age with a diagnosis of hematologic malignancy undergoing treatment at a single institution. For this analysis, we included pts with NDMM and AL amyloidosis treated with dara-based combination therapy between January 2020 and January 2022. We obtained baseline disease- and patient-related characteristics. Toxicity was evaluated by chart review up to the first 6 cycles and adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events (CTCAE v5.0). For patients receiving >1 cycle, response assessment was ascertained using International Myeloma Working Group (IMWG) uniform response criteria. All patients were followed until progression, death or last follow up and progression-free survival (PFS) and overall survival (OS) were measured using Kaplan Meier methods. Health-related quality of life (HRQoL) was measured using Patient-Reported Outcomes Measurement Information System (PROMIS) global 10 and quantified using physical health (PH) and mental health (MH) t-scores at baseline and 3 month follow up. Variables were compared in each race by using independent and paired sample t-tests as appropriate. Results: Over the study period, 36 black pts (NDMM=32; AL=4) and 50 white pts (NDMM=44; AL=6) received upfront dara-based combination therapy. There were no differences in age or sex, IGH translocations, but there was a higher incidence of cytogenetic high-risk disease among the black pts in our cohort (p=0.02). Black pts presented with more advanced disease at the time of presentation - hypercalcemia 33% vs. 14%, p=0.04; renal dysfunction 56% vs. 28%, p=0.01; anemia 67% vs. 38%, p=0.01). Incidence of bone disease was similar between the groups (p=0.69) (Table 1) Among blacks, the most utilized regimen was DaraVRd (56%), DaraRd (17%), DaraKRd (11%) and DaraVCd (11%). While for the white pts, it was DaraVRd (52%), DaraRd (12%), DaraKRd (8%) and DaraVCd (22%). Blacks had a similar incidence of ≥grade 3 non-hematologic AEs (p=0.21), with fatigue, diarrhea and leg edema being the most common. There is a trend towards higher ≥grade 3 hematologic AEs which did not reach statistical significance (p=0.05). After 6 cycles of therapy, overall response rate was comparable (100% vs. 94%, p=0.81) among the two groups (≥VGPR 47% vs. 62%, p=0.36). With 18 month median follow up, there was no difference in median PFS and OS, both not reached (Figure 1). Complete quality of life (QoL) t-scores were available at baseline for 55 pts (20 blacks and 35 whites). The baseline PH and MH related QoL scores were comparable between whites and blacks (p= 0.51; p=0.58, respectively). From baseline to 3 months follow up, PH t-scores improved in both whites as well as blacks although the difference was not statistically significant. Meanwhile, MH t-scores remained largely unchanged from baseline to follow up in both groups. Conclusions: We report the largest cohort to date of black pts with dysproteinemia systematically treated with frontline dara. Our data shows the feasibility of this strategy in a single institution setting with comparable safety, efficacy and HRQoL with the use of upfront dara-based combinations in black and white pts. Our data supports comparable clinical outcomes among black pts when treated with novel therapeutic combinations despite a higher proportion of high risk cytogenetic abnormalities in our cohort without an increase in AEs. Minority representation in cancer clinical trials as well as access to approved novel therapies can significantly help mitigate disparities in outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Renal Toxicity with Carfilzomib in Multiple Myeloma: Secondary Analysis of SWOG S1304 Comparing Low-Dose Versus High-Dose Carfilzomib

Introduction: Randomized controlled trials (RCTs) testing carfilzomib-based combination regimens in myeloma have demonstrated a signal of increased renal toxicity, with a relative risk of 2.3 for grade≥3 toxicities with carfilzomib-based versus non-carfilzomib-based regimens (Ball et al. Annals of Hematology. 2020). Nonetheless, there are insufficient data on detailed characterization of carfilzomib-induced renal toxicity, especially in patients treated with carfilzomib alone or with dexamethasone, without the confounding effect of additional classes of anti-myeloma therapy. The objective of our study was to estimate the incidence, timing, nature, and potential risk-factors of carfilzomib-induced renal toxicity using data from S1304 which compared two doses of carfilzomib (56 mg/m2 (K56) vs 27 mg/m2 (K27) twice-weekly), both with dexamethasone, in relapsed/refractory myeloma (Ailawadhi et al. Clinical Cancer Research. 2020). Methods: Individual patient-level data from S1304 trial (NCT01903811) were utilized to estimate the incidence, nature, and timing of renal toxicities. The toxicity of interest was acute kidney injury (AKI), in which, we included the adverse event description of "increased creatinine". Baseline characteristics in patients who developed AKI versus those who didn't were compared using Fisher's exact test. Results: Our analysis on renal toxicity included 123 patients, with 57 patients randomized to K56 and 66 to K27 arms. All-grade AKI/increased creatinine (hereafter, referred to as AKI) was seen in 21 patients overall (17.1%), with grade≥3 toxicity seen in 6 patients (4.9%). By treatment arms, the incidence of all-grade and grade≥3 AKI for K56 was 21.1% and 5.3% respectively, whereas for K27 arm it was 13.6% and 4.5%, respectively. The median time to onset of AKI was 2.5 (range, 2-3) and 2 (range, 1-7) cycles for all-grade and grade≥3 respectively. Kidney toxicities of interest other than AKI were CKD and proteinuria. The overall incidence of all-grade CKD and proteinuria were low at 1.6% and 2.4% respectively, with no grade ≥3 events. The incidence of CKD in K56 and K27 arms was 1.8% and 1.5% respectively, whereas that for proteinuria was 1.8% and 3% respectively. The median time to onset of CKD was 3.5 cycles (range, 3-4) and that of proteinuria was 2 cycles (range, 1-9). Subsequently, we investigated any potential differences in baseline patient-specific, disease-specific, or treatment-specific characteristics between patients who developed AKI versus those who did not (Table 1). The only variable that showed a near-significant difference between the two was percent bone marrow plasma cells (BMPC), with %BMPC in the two groups being 41% vs 18% respectively (p=0.052). There was no significant difference in the proportion of patients receiving K56 between the two groups (56% vs 45% respectively; p=0.45). Next, we performed a 3-month landmark analysis to estimate progression-free survival (PFS) stratified by development of any-grade AKI that was at least possibly attributable to study treatment prior to 3 months following randomization. There was no significant difference in median PFS between patients who developed kidney toxicity versus those who did not. Conclusion: In summary, we showed that ≥grade 3 AKI is observed in ~5% of patients receiving carfilzomib plus dexamethasone, with most events occurring early at a median of about 2 cycles from treatment initiation. Furthermore, high tumor burden at baseline is a potential predictor of AKI with carfilzomib, whereas dose-intensity of carfilzomib was not different between patients who developed AKI versus those who didn't. Our findings are comparable to that of the ARROW trial which tested once weekly (70 mg/m2) versus twice-weekly (27 mg/m2) carfilzomib, and demonstrated grade≥3 AKI in 4% and 6% of patients, respectively. Future studies should investigate additional risk-factors and reversibility of carfilzomib-induced renal toxicity as well as impact on survival in larger patient cohorts. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Afatinib and Dacomitinib Efficacy, Safety, Progression Patterns, and Resistance Mechanisms in Patients with Non-Small Cell Lung Cancer Carrying Uncommon EGFR Mutations: A Comparative Cohort Study in China (AFANDA Study).

(1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, has also shown promising potential for uncommon EGFR mutations. However, no comparative study has been conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 patients with uncommon EGFR mutations admitted to two tertiary hospitals in China, and an external validation afatinib cohort (ex-AC), extracted from the Afatinib Uncommon EGFR Mutations Database (N = 1140). The AFANDA cohort was divided into an afatinib cohort (AC) and a dacomitinib cohort (DC) for internal exploration. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were assessed for comparison. Progression patterns and resistance mechanisms were explored. (3) Results: In total, 286 patients with advanced NSCLC carrying uncommon EGFR mutations treated with afatinib or dacomitinib were enrolled, including 79 in the AFANDA cohort (44 in the DC, 35 in the AC) and 207 in the ex-AC. In internal exploration, the ORR of the DC was significantly higher than that of the AC (60.5 vs. 26.7%, p = 0.008), but there was no significant difference in median PFS between the DC and the AC (12.0 months vs. 10.0 months, p = 0.305). Multivariate analysis confirmed an independent favorable effect of dacomitinib on PFS (hazard ratio (HR), 1.909; p = 0.047). In external validation, multivariate analysis confirmed the independent prognostic role of dacomitinib in PFS (HR, 1.953; p = 0.029). Propensity score matching analysis confirmed the superiority of dacomitinib over afatinib in terms of PFS in both univariate and multivariate analyses. Toxicity profiling analysis suggested more G1 (p = 0.006), but fewer G3 (p = 0.036) AEs in the DC than in the AC. Progression patterns revealed that the incidence of intracranial progression in the AC was significantly higher than that in the DC (50 vs. 21.1%, p = 0.002). Drug resistance analysis indicated no significant difference in the occurrence of T790M between the AC and the DC (11.8 vs. 15.4%, p = 0.772). (4) Conclusions: Compared with afatinib, dacomitinib demonstrated a more favorable activity with manageable toxicity and different progression patterns in patients with NSCLC carrying uncommon EGFR mutations.

Eribulin in Patients with Liposarcoma and Leiomyosarcoma: A Retrospective Single-Center Experience

Introduction: Soft tissue sarcomas are rare and heterogenous malignancies with a poor prognosis in advanced disease stages. Eribulin is used in metastatic liposarcoma (LPS) patients, who have failed first-line chemotherapy and has been approved for use in patients with LPS in the USA and Europe due to its efficacy in this histological subtype in a phase 3 trial. We have evaluated efficacy and tolerability of eribulin in LPS and leiomyosarcoma (LMS) patients in the routine clinical setting at our department. Methods: In this retrospective single-center analysis, efficacy and safety of eribulin were retrospectively evaluated in advanced LPS and LMS patients at the Division of Oncology, Medical University of Vienna. Results: A total of 32 adult patients treated with eribulin were identified and included in this analysis. Overall response rate was 9.4% for all patients, with one patient with LPS and two patients with LMS showing a partial response. Disease control rate (partial response plus stable disease) for all patients was 50% (LPS: 47.1%; LMS 53.3%). No statistically significant difference in median progression-free survival and overall survival was detected between patients with LPS and LMS (p = 0.807 and p = 0.519, respectively). Patients with LMS (n = 2) had received fewer previous therapy lines than patients with LPS (n = 14) (≤ previous treatment lines, p < 0.001). Toxicity was generally manageable, and grade 3 + 4 events were rare. Conclusion: The activity and tolerability of eribulin in LPS as in well in LMS patients in the routine clinical setting is comparable to outcomes reported in published phase 3 trials.

EGFR uncommon alterations in advanced non-small cell lung cancer and structural insights into sensitivity to diverse tyrosine kinase inhibitors.

Background: Approximately 10% of patients with non-small cell lung cancer (NSCLC) harbor uncommon epidermal growth factor receptor (EGFR) alterations. This study aims to investigate the therapeutic responses and predict the binding activity of different tyrosine kinase inhibitors (TKIs) for EGFR uncommon alterations. Methods: Between May 2014 and June 2021, clinical outcomes of NSCLC patients harboring EGFR uncommon alterations who received diverse treatment modalities: first-generation (1G) EGFR-TKI, second-generation (2G) EGFR-TKI afatinib, chemotherapy, and 1G TKI in combination with chemotherapy as the initial therapy were retrospectively analyzed, and structural analysis for the binding activity of major uncommon subtypes G719A, S768I, and L861Q to different TKIs were predicted. Results: A total of 102 NSCLC patients harboring EGFR uncommon alterations with treatment and survival outcomes were included and analyzed. The majority of patients presented compound mutations (54.9%), and G719X plus S768I was the predominant subtype (n = 33, 32.3%). There was a significant difference in median progression-free survival (mPFS) between therapeutic patterns (p = 0.015) and EGFR alteration subtypes (p = 0.017). Rather than almonertinib and furmonertinib, afatinib, dacomitinib and osimertinib revealed favorable binding activity to G719A mutation. In contrast, S768I and L861Q mutation indicated an unaffected binding activity to these diverse kinds of EGFR TKIs. Conclusion: Together with afatinib, 1G-TKIs combined with chemotherapy might be another effective option for NSCLC patients harboring EGFR uncommon alterations. Based on computational findings, afatinib, dacomitinib, and osimertinib might confer favorable activity to G719A, S768I, and L861Q, whereas almonertinib and furmonertinib revealed less activity to G719A.