Improvement In Disease-free Survival Research Articles

HLA-I and breast cancer prognosis: A systematic review and meta-analysis

BackgroundBreast cancer (BC) is a significant global health issue, accounting for 1 in 8 cancer diagnoses worldwide. HLA class I molecules are typically expressed on the cell surface, but cancer cells can develop mechanisms to evade recognition by CTLs, including the downregulation of HLA class I expression. In this context, we aimed to conduct a systematic review and meta-analysis to clarify the role of HLA class I expression in clinical outcomes for patients with BC. MethodsA comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases. Effect sizes, along with I2 and Tau2 statistics, were used to assess heterogeneity through a DerSimonian and Laird random-effects model. Statistical analyses were performed using R statistical software, version 4.2.3. ResultsAmong the 8 included studies, most of the analyzed samples consisted of ductal carcinoma cases (1588, 86.39 %), from the luminal (A or B) intrinsic subtype (1865, 69.07 %), with no lymph node metastasis (2658, 57.24 %), no HER2 overexpression (2594, 67.46 %), negative Ki67 status (1721, 71.26 %), and positive hormone receptor status (4732, 64.05 %). The analysis revealed a significant reduction in disease-free survival (HR 0.57; 95 % CI 0.34 to 0.95; p = 0.034; I2 = 84 %) in the group with low HLA-I expression. However, no significant difference was found between the groups with high and low HLA-I expression regarding overall survival (HR 0.77; 95 % CI 0.28 to 2.14; p = 0.62; I2 = 86 %). ConclusionsThis systematic review and meta-analysis demonstrated that HLA class I expression is associated with a significant improvement in disease-free survival, though no significant effect on overall survival was observed.

Evidence from resected early-stage non-small cell lung cancer with EGFR mutation: a literature review.

Non-small cell lung cancer (NSCLC) in early-stages (I-IIIA) with epidermal growth factor receptor (EGFR) mutation may have specific epidemiological, clinical characteristics and treatment implications. This review aims to summarise the available evidence on these particularities, especially focusing on patient characteristics, treatment outcomes and safety with EGFR-tyrosine-kinase inhibitor (TKI). An exhaustive search of international bibliographic databases, as well as in abstracts of communications from major international congresses was performed for evidence related to EGFR-mutated NSCLC or early-stage NSCLC published in English before December 31st, 2023. Early-stage NSCLC with EGFR mutation presents with a variable incidence depending on geographical aspects. The clinical, radiological and molecular features differ slightly from both early-stage NSCLC without EGFR mutation and advanced NSCLC with EGFR mutation. Adjuvant treatment with the third-generation EGFR-TKI osimertinib has led to improvements in disease-free survival and overall survival (OS) in these patients, representing a practice changing and a new standard of care in clinical practice. No new safety signals have been reported with EGFR-TKI in the adjuvant setting. Clinical trials are ongoing to explore new therapeutic options in the adjuvant and neoadjuvant setting as well as the optimal duration of adjuvant osimertinib. Detection of EGFR mutation in early-stage NSCLC is an important goal due to the different characteristics and additional therapeutic options that improve patient outcomes and follow-up.

The significance of risk stratification through nomogram-based assessment in determining postmastectomy radiotherapy for patients diagnosed with pT1 − 2N1M0 breast cancer

ObjectiveTo explore the high-risk factors affecting the prognosis of pT1 − 2N1M0 patients after mastectomy, establish a nomogram prediction model, and screen the radiotherapy benefit population.MethodThe clinical data of 936 patients with pT1 − 2N1M0 who underwent mastectomy in the fourth hospital of Hebei Medical University from 2010 to 2016 were retrospectively analyzed. There were 583 patients received postmastectomy radiotherapy(PMRT), and 325 patients without PMRT. Group imbalances were mitigated using the propensity score matching (PSM) method, and the log-rank test was employed to compare overall survival (OS) and disease-free survival (DFS) between the cohorts. The efficacy of PMRT across various risk groups was evaluated using a nomogram model.ResultThe median follow-up period was 98 months, Patients who received PMRT demonstrated significantly improved 5-year and 8-year OS and DFS compared to those who did not (P < 0.001). Multivariate analysis revealed that age, primary tumor site, positive lymph node, stage, and Ki-67 level independently influenced OS, while age, primary tumor site, and stage independently affected DFS. PMRT drastically enhanced OS in the high-risk group (P = 0.001), but did not confer benefits in the low-risk and intermediate risk groups (P = 0.057, P = 0.099). PMRT led to a significant improvement in disease-free survival (DFS) among patients in the intermediate and high-risk groups (P = 0.036, P = 0.001), whereas the low-risk group did not experience a significant benefit (P = 0.475).ConclusionAge ≤ 40 years, tumor located in the inner quadrant or central area, T2 stage, 2–3 lymph nodes metastasis, and Ki67 > 30% were the high-risk factors affecting the prognosis of this cohort of patients. In OS nomogram, patients with a risk score of 149 or higher who received PMRT exhibited improved OS. Similarly, in DFS nomogram, patients with a risk score of 123 or higher who received PMRT demonstrated enhanced DFS.

Does Adjuvant Chemotherapy Benefit Patients with T4 N0 Colon Cancer?

Background and Objectives: Colorectal cancer (CRC) poses a major global health challenge, with high incidence rates and ongoing treatment debates. Adjuvant chemotherapy benefits for high-risk subgroups, particularly stage II disease, remain controversial. This study seeks to clarify this issue by specifically examining the impact of adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS) in patients diagnosed with T4 colon cancer. Materials and Methods: This retrospective study analyzed patients undergoing radical surgery for T4 colon cancer between 2002 and 2023. Results: Our study of 184 pT4 pN0 colon cancer patients revealed that 79.3% received adjuvant chemotherapy. Multivariate analysis demonstrated significant DFS improvement: a 60% reduction in risk for those who received adjuvant therapy (0.40 95% CI: 0.25-0.62, p < 0.001). Lymphovascular invasion (LVI) and adjuvant treatment were also significantly associated with OS. Adjuvant treatment reduced mortality by 60% (HR: 0.40, 95% CI: 0.23-0.68, p = 0.001). Patients with LVI had a 1.9-fold increase in mortality (HR: 1.94, 95% CI: 1.17-3.20, p = 0.011). These findings underscore the potential value of adjuvant chemotherapy and highlight the importance of treatment completion in managing T4 colon cancer. Conclusions: Our study identifies LVI and adjuvant chemotherapy as key prognostic factors in T4 colon cancer patients. These results support the consideration of adjuvant chemotherapy in this patient population.

Systematic review on the efficacy and safety of ixabepilone-based chemotherapy regimen in triple-negative breast cancer

Context: Triple-negative breast cancer (TNBC) has poor prognosis, high mortality, and recurrence rates. Ixabepilone or ixempra could be a promising agent for TNBC, especially in the taxane- and/or anthracycline-resistant population. Aims: To evaluate the efficacy and safety of ixabepilone-based chemotherapy compared to ixabepilone-free chemotherapy in TNBC patients. Methods: This review followed the preferred reporting items for systematic reviews and meta-analysis guidelines. The eligibility criteria included randomized control trials (RCTs) in 2013-2023 comparing ixabepilone-based with ixabepilone-free chemotherapy regimen in TNBC. Results: This study identified four eligible RCTs. One study showed that patients treated with ixabepilone had a significant improvement in disease-free survival, had a better response, and a lower risk of disease recurrence compared to those treated with taxane-based regimen. However, two studies showed no differences in terms of overall survival (OS), disease-free survival, and pathological complete responses rates in both treatment arms. Ixabepilone addition to capecitabine significantly prolonged progression-free survival and objective response rate in TNBC patients, but did not significantly improve OS (n = 1). Conclusions: The effectiveness and safety of ixabepilone-based chemotherapy versus ixabepilone-free treatment for triple-negative breast cancer (TNBC) patients vary among studies. More research is needed to better understand the effectiveness and safety of ixabepilone-based chemotherapy versus ixabepilone-free treatment in TNBC patients.

Shifting Paradigms in TNBC Treatment: Emerging Alternatives to Capecitabine in the Post-Neoadjuvant Setting.

Triple-negative breast cancer (TNBC) remains a clinically challenging subtype due to its aggressive nature and limited treatment options post-neoadjuvant failure. Historically, capecitabine has been the cornerstone of adjuvant therapy for TNBC patients not achieving a pathological complete response (pCR). However, the integration of new modalities such as immunotherapy and PARP inhibitors has prompted a re-evaluation of traditional post-neoadjuvant approaches. This review synthesizes data from pivotal clinical trials and meta-analyses to evaluate the efficacy of emerging therapies in the post-neoadjuvant setting. We focus on the role of immune checkpoint inhibitors (ICIs), PARP inhibitors (PARPis), and antibody-drug conjugates (ADCs) alongside or in place of capecitabine in TNBC treatment paradigms. The addition of ICIs like pembrolizumab to neoadjuvant regimens has shown increased pCR rates and improved event-free survival, posing new questions about optimal post-neoadjuvant therapies. Similarly, PARPis have demonstrated efficacy in BRCA-mutated TNBC populations, with significant improvements in disease-free survival (DFS) and overall survival (OS). Emerging studies on ADCs further complicate the adjuvant landscape, offering potentially efficacious alternatives to capecitabine, especially in patients with residual disease after neoadjuvant therapy. The challenge remains to integrate these new treatments into clinical practice effectively, considering factors such as drug resistance, patient-specific characteristics, and socio-economic barriers. This review discusses the implications of these therapies and suggests a future direction focused on personalized medicine approaches in TNBC. As the treatment landscape for TNBC evolves, the role of capecitabine is being critically examined. While it remains a viable option for certain patient groups, the introduction of ICIs, PARPis, and ADCs offers promising alternatives that could redefine adjuvant therapy standards. Ongoing and future trials will be pivotal in determining the optimal therapeutic strategies for TNBC patients with residual disease post-neoadjuvant therapy.

Improved Survival With Adjuvant Cyclooxygenase 2 Inhibition in PIK3CA-Activated Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of recurrence and suggest that PIK3CA mutational status is predictive of better response to COX-2 inhibition. To prospectively test whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival, the National Cancer Institute sponsored the CALGB/SWOG 80702 trial (ClinicalTrials.gov identifier: NCT01150045) for patients with stage III resected colon cancer. Although the primary hypothesis for all patients did not show a statistically significant improvement in disease-free survival (DFS) with celecoxib, subgroup analysis by PIK3CA mutational status was a preplanned study. PIK3CA gain-of-function mutations were detected in 259 of 1,197 tumors with available whole-exome sequencing data. When stratified by PIK3CA status, patients with PIK3CA gain-of-function mutations treated with celecoxib exhibited improved DFS (adjusted hazard ratio [HR], 0.56 [95% CI, 0.33 to 0.96]) compared with PIK3CA wildtype patients (adjusted HR, 0.89 [95% CI, 0.70 to 1.14]), although the interaction test was nonsignificant (Pinteraction = .13). Overall survival was similarly improved for patients with PIK3CA gain-of-function mutations (adjusted HR, 0.44 [95% CI, 0.22 to 0.85]) compared with PIK3CA wildtype patients (adjusted HR, 0.94 [95% CI, 0.68 to 1.30]; Pinteraction = .04). Although the test for heterogeneity in DFS did not reach statistical significance, the results suggest potential utility of PIK3CA to consider selective usage of COX-2 inhibitors in addition to standard treatment for stage III colon cancer.

IMpower010: Final disease-free survival (DFS) and second overall survival (OS) interim results after ≥5 years of follow up of a phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA non-small cell lung cancer (NSCLC).

LBA8035 Background: IMpower010 (NCT02486718) met its primary endpoint of significant DFS improvement with atezo vs BSC after adj chemotherapy in resected NSCLC in the PD-L1 TC ≥1% and all-randomized stage II-IIIA populations, leading to worldwide approval of adj atezo for PD-L1 TC ≥1% or PD-L1 TC ≥50% stage II-IIIA NSCLC. At OS IA1, a trend favoring atezo was seen in the PD-L1 TC ≥1% stage II-IIIA population. Here we report findings from the DFS FA and OS IA2. Methods: The IMpower010 study design has been previously described (Felip et al, Lancet 2021). The primary DFS and secondary OS endpoints were tested hierarchically: DFS in the PD-L1 TC ≥1% (SP263) stage II-IIIA, then in the all-randomized stage II-IIIA, and then in the intent-to-treat (ITT; stage IB-IIIA) populations, followed by OS in the ITT population. Secondary endpoints included 3- and 5-y DFS and DFS in the PD-L1 TC ≥50% (SP263) stage II-IIIA population. OS in the ITT population could only be formally tested if the significance boundary for DFS in that population was crossed. Results: At the DFS FA and OS IA2 (clinical cutoff date: Jan 26, 2024), with a minimum follow-up of 60 mo, DFS and OS for the PD-L1 TC ≥1% and TC ≥50% stage II-IIIA populations were consistent with previously observed benefit; the difference in median (m) DFS between arms in the PD-L1 TC ≥1% population was 31.2 mo (Table). In the ITT population, the significance boundary for DFS was not crossed and OS was similar between arms, although data were immature. The safety profile of atezo was consistent with prior analyses. Conclusions: These results provide the first cancer immunotherapy data with ≥5 y of follow-up from a Phase III study in resectable NSCLC. Although the statistical boundary for the ITT population was not crossed, DFS benefit with adj atezo continues to translate into a positive OS trend vs BSC in the PD-L1 TC ≥1% and TC ≥50% stage II-IIIA populations. These results further support the use of adj atezo in PD-L1–selected populations. Clinical trial information: NCT02486718 . [Table: see text]

Reduced intensity conditioning regimen of fludarabine, busulfan, ATG based haploidentical stem cell transplantation for older or unfit patients.

Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of anti-thymocyte globulin (ATG) based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG-based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in older or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG-based haploidentical HSCT. We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30mg/m²/kg 6 days combined with busulfan 3.2mg/kg 2 days (Bu2) or 3 days (Bu3). ATG-Fresenius (ATG-F) was administered 10mg/kg in total, ATG-thymoglobulin (ATG-T) was administered 6mg/kg in total. The median age of patients in the entire cohort was 60 (32-67) years with a median follow-up of 496 (83-2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. A total of 32 patients underwent Bu2 RIC haplo-HSCT and 31 patients were treated with Bu3 RIC haplo-HSCT. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8 - 85.1%) and 61.4% (95% CI, 48.8 - 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8% (95% CI, 4.8 - 19.6%) and 9.7% (95% CI, 0.0 - 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9 - 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5 - 33.7%) and 11.6% (95% CI, 2.2 - 21.9%) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5-85.3%) in Bu2 and 85.5%(95% CI:73.0-100%) in Bu3 group respectively(P = 0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0-74.8%) in Bu2 and 72.6% (95% CI:55.5-95.5%) in Bu3 group respectively (P = 0.045). The 2-year IR of Bu2group was significantly higher than Bu3group(P = 0.045). However, the2-year NRM were not significantly different between Bu2 and Bu3 group(P > 0.05). In multivariable analysis, RIC regimen of Bu3 had superior OS and DFS than Bu2 group respectively [HR 0.42, 95% CI 0.18-0.98; P = 0.044; HR 0.34, 95% CI 0.14-0.86; P = 0.022]. Besides, RIC regimen of Bu3 had lower IR than Bu2 group [HR 0.34, 95% CI 0.13-0.89; P = 0.029]. The RIC regimen of ATG-based haploidentical HSCT is a safe and effective treatment option for patients who are older or have poor functional status. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in OS and DFS, thus providing more favorable post-transplantation clinical outcomes.

FLT3 inhibitor maintenance after allogeneic stem cell transplantation in FLT3-mutated acute myeloid leukemia (AML) patients.

The somatic mutation of fms-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia (AML) is associated with increased risk of relapse and lower survival rates. FLT3i as maintenance after allogeneic hematopoietic stem cell transplant (allo-HSCT) are under study to prevent disease relapse, but real-world data are lacking. We performed a single center, retrospective cohort study and analyzed patients who had FLT3-mutated AML and underwent allogeneic-HSCT between January 2011 to June 2022 at the University of Chicago. We identified 23 patients who received FLT3i maintenance therapy post-allo-HSCT and compared their outcomes against 57 patients who did not. Primary outcome was disease-free survival (DFS). Secondary outcomes include overall survival (OS) and relapse rate. FLT3i maintenance therapy was started at a median 59 days (range, 29-216 days) after allo-HSCT with median duration of 287 days (range, 15-1,194 days). Maintenance therapy was well tolerated. Overall, the improvement in DFS rates for patients after they were placed on FLT3i maintenance therapy was not significant [hazard ratio (HR) for relapse or death =0.65, 95% confidence interval (CI): 0.32-1.31, P=0.23]. However, when adjusted for the conditioning regimen and donor status, the differences were statistically significant with improvement in DFS and OS for patients on FLT3i maintenance (HR for OS =0.42, 95% CI: 0.18-0.95, P=0.04). When adjusting for conditioning regimen and donor status, there was a significant improvement in DFS and OS for patients who received FLT3i maintenance therapy compared to those who did not. Randomized prospective studies may provide more insight.

Extent of lymphadenectomy for surgical management of right-sided colon cancer: Multicenter, open label, randomized, controlled trial.

3575 Background: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. Methods: This randomized, controlled, unblinded, phase 3, superiority trial involved 17 hospitals in China. Totally 1,072 patients diagnosed with stage T2-T4aNanyM0 or TanyN+M0 right-sided colon cancer were enrolled from January 11, 2016, through December 26, 2019. Participants were randomly assigned (1:1 ratio) to undergo either CME (n=536) or D2 dissection (n=536) during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). Results: Among 1072 patients, 77 were excluded after randomization. The remaining 995 patients (median age 61years, 59% male) were included in the primary analysis (CME [n=495] vs. D2 dissection [n=500]). The 3-year primary outcome assessment was completed for 97% patients. No significant differences were found between the groups in 3-year DFS (86.1% in CME group vs. 81.9% in D2 group; HR = 0.74; 95% confidence interval [CI]: 0.54-1.02; P = 0.06) or in 3-year OS (94.7% in CME group vs. 92.6% in D2 group; HR = 0.70; 95% CI: 0.43-1.16; P = 0.17). Conclusions: For primary surgical excision of right-sided colon cancer, complete mesocolic excision did not improve disease free survival, compared to standard D2 lymph node dissection. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement. Trial Registration: ClinicalTrials.gov Identifier: NCT02619942. Clinical trial information: NCT02619942 .

Molecular residual disease (MRD) analysis from the ADAURA trial of adjuvant (adj) osimertinib in patients (pts) with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC).

8005 Background: Osimertinib (osi) is a third-generation, central nervous system-active EGFR-TKI, that potently and selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations. Adj osi (3 years [yrs]) is recommended for resected EGFRm stage IB–IIIA NSCLC, based on significant improvements in disease-free survival (DFS) and overall survival (OS) in the Phase III ADAURA study (NCT02511106). A trend towards an increased DFS event rate beyond 3 yrs suggests some pts may benefit from longer adj osi treatment (tx). We explored if plasma ctDNA-based, tumor-informed MRD could predict disease recurrence. Methods: Eligible pts (≥18 yrs [≥20 in Japan/Taiwan], WHO PS 0/1 with completely resected EGFRm [Ex19del/L858R] stage IB, II or IIIA [AJCC 7th edition] NSCLC) were randomized 1:1 to osi 80 mg once daily or placebo (pbo) until disease recurrence, tx completion (up to 3 yrs), or a discontinuation criterion was met. Personalized MRD panels (RaDaR, NeoGenomics) were used, comprised of ≤50 tumor-specific variants, based on whole exome sequencing of resected tumor tissue (variants identified in germline DNA removed). Plasma sample collection: baseline (BL; at randomization surgery and adj Ctx, if received), on tx (every 12 weeks [wks]), tx discontinuation, and post-tx completion (wk 12, wk 24, then every 24 wks until 5 yrs). Plasma samples were analyzed for detection of ctDNA (MRD+). Molecular recurrence or DFS (MRD/DFS) was defined as time from randomization to post-BL MRD+, disease recurrence, or death and was compared across arms. DFS was investigator-assessed. Results: Of 682 pts randomized, 245 (36%) had samples required to produce MRD panels, which were evaluable for 220 (32%) pts across both arms. In the osi vs pbo arms, 5/112 (4%) vs 13/108 (12%) pts were MRD+ at BL; 4/5 pts became MRD– during osi tx vs 0/13 pts on pbo. On tx, MRD detection had clinical sensitivity of 65% (62 MRD+/96 DFS+), specificity of 95% (118 MRD–/124 DFS–) and preceded a DFS event by a median (95% CI) of 4.7 (2.2, 5.6) months (mos) across both arms. Median follow-up time from randomization was 44.2 (95% CI 42.4, 49.1) and 19.1 (95% CI 11.1, 28.3) mos for osi and pbo arms, respectively. Overall, 86% (95% CI 78, 92) vs 36% (95% CI 27, 45) pts in the osi vs pbo arms were MRD/DFS event free at 36 mos (HR: 0.23; 95% CI 0.15, 0.36). MRD/DFS events in the osi arm were detected at any time post-BL in 28 (25%) pts, of whom 19/28 (68%) had events post-adj osi. Most (11/19 [58%]) MRD/DFS events detected occurred within 12 mos of osi tx completion. Conclusions: MRD+ preceded DFS events in most pts with a median lead time of 4.7 mos across both arms. MRD– was maintained for most pts during adj osi tx with the majority of MRD/DFS events occurring after osi tx completion. MRD detection could potentially identify a subset of pts likely to benefit from longer adj osi. Clinical trial information: NCT02511106 .

Tislelizumab plus tyrosine kinase inhibitor versus active surveillance in patients with ablated high-risk hepatocellular carcinoma: An open-label, parallel controlled, prospective cohort study.

e16238 Background: In IMbrave050, adjuvant atezolizumab plus bevacizumab demonstrated improvement in recurrence-free survival vs active surveillance in patients at high risk of hepatocellular carcinoma (HCC) recurrence following resection or ablation with curative intent. However, there is limited study on programmed cell death protein 1 (PD-1) inhibitor plus tyrosine kinase inhibitor (TKI) as postoperative adjuvant therapy for HCC. We aimed to assess the safety and efficacy of tislelizumab (a PD-1 inhibitor) plus TKI as adjuvant therapy versus active surveillance in patients at high risk of HCC recurrence after curative ablation. Methods: This study enrolled patients with HCC at high risk of recurrence following curative ablation. Patients were paralleled to Arm A (tislelizumab plus TKI) or Arm B (active surveillance). Patients in Arm A received tislelizumab (200 mg, IV, q3w) plus TKI for three months (4 cycles) following curative ablation, while those patients in Arm B underwent active surveillance. Primary endpoints were safety and tumor recurrence rate. Secondary endpoint was disease free survival (DFS). Exploratory endpoints included biomarkers related to the recurrence. Results: A total of 48 patients were enrolled with a median follow-up time of 283 days (IQR: 123-460 days, clinical cutoff date: 1 Jan 2024). Nine patients (37.5%) reported at least one adverse event of any degree in Arm A and three patients (12.5%) reported in arm B, most of which were mild. Only one patient in arm A experienced a grade 3 treatment-related adverse event, which improved after administration of symptomatic treatment. The recurrence rate of patients in arm A was 20.83%, which was significantly lower than the 58.3% in arm B (OR = 0.188 [95% CI: 0.052 - 0.674], P = 0.017). Four cycles of adjuvant tislelizumab plus TKI therapy was associated with significantly improved DFS (median, not evaluable [NE]) compared with active surveillance (median, 188 days [95% CI: 78.4 - 297.6 days]; HR = 0.396 [95% CI: 0161 - 0.973], P = 0.044). The absence of tislelizumab treatment (OR = 4.823 [95% CI: 1.091 - 21.329], P = 0.038) and multiple tumor lesions (OR = 7.651 [95% CI: 1.270 - 46.114], P = 0.026) were risk factors for recurrence of HCC after curative ablation. Conclusions: The safety of tislelizumab plus TKI combination therapy were generally manageable. Statistically significant and clinically meaningful improvement in tumor recurrence rate and DFS were seen in patients receiving combination therapy vs active surveillance. This study was a positive attempt to undergo short-course PD-1 inhibitor plus TKI combination therapy in patients with HCC at high risk of recurrence following curative ablation, showing promising efficacy in preventing HCC recurrence. Clinical trial information: NCT06059885 .

Abstract A008: Racial differences in characteristics and outcomes of adjuvant nivolumab for muscle-invasive urothelial carcinoma (MIUC) in the real-world setting

Abstract Objectives: Historically, African-American/Black patients with bladder cancer have worse clinical outcomes compared with White/Caucasian patients. In the CheckMate 274 trial, nivolumab demonstrated a significant improvement in disease-free survival compared with placebo among patients with MIUC at high risk of recurrence following radical surgery; however, African-American/Black patients were underrepresented (&amp;lt; 1%). The objective of this analysis was to describe the characteristics and outcomes of MIUC patients treated with adjuvant nivolumab across different racial subgroups in a real-world setting. Methods: This US retrospective medical chart review included African-American/Black and White/Caucasian patients with MIUC treated with adjuvant nivolumab following radical resection between 01-Sep-2021 and 10-Sep-2022. Patient characteristics and outcomes were abstracted from the medical charts by treating oncologists. Patient characteristics and landmark survival estimates based on Kaplan-Meier analyses were summarized descriptively. Results: The analysis included 223 patients (African-American/Black: 62; White/Caucasian: 161). A numerically higher proportion of African-American/Black vs White/Caucasian patients, respectively, was male (74.2% vs 66.5%), less than 60 years old (27.4% vs 20.5%), unemployed (16.1% vs 5.6%), and had Medicaid at therapy initiation (14.5% vs 6.2%). Similar proportions in both groups had ECOG performance status 0-1 (82.3% vs 82.6%), received neoadjuvant therapy (58.1% vs 56.5%), and completed adjuvant therapy (67.7% vs 66.5%). The median follow-up time (12.5 months vs 13.1 months) and median duration of adjuvant therapy (11.0 months vs 11.3 months) were comparable. Similar estimates were observed for 12-month overall survival (96.7% vs 91.4%), 12-month disease-free survival (88.3% vs 88.4%), and 12-month distant metastasis-free survival (88.3% vs 88.4%). Conclusions: Despite higher rates of socio-economic risk factors among African-American/Black patients, this real-world study suggests similar effectiveness of adjuvant nivolumab among MIUC patients across African-American/Black and White/Caucasian patient populations. Citation Format: Regina Barragan-Carrillo, Alexander Chehrazi-Raffle, Bruce Feinberg, William S. John, Taavy A. Miller, Sarah Lucht, Prathamesh Pathak, Emily Bland, Sarah Gordon, JaLyna Laney, Andrew J. Klink, Hedyeh Ebrahimi, Nisha Singh, Carmelo Alonso, Miraj Patel, Lisa Rosenblatt, Xin Yin. Racial differences in characteristics and outcomes of adjuvant nivolumab for muscle-invasive urothelial carcinoma (MIUC) in the real-world setting [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A008.

Preferences of physicians for treatment-related toxicity vs. recurrence in melanoma (GERMELATOX-A): the doctors’ perspective

IntroductionAdjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influenced by the risk of toxicity. Therefore, the role of physicians in treatment decisions of patients is crucial. This study investigated for the first time in a multicenter setting the attitudes and preferences of dermatooncologists in Germany and Switzerland regarding adjuvant treatment with (c)ICI and TT.MethodsIn the GERMELATOX-A study, 108 physicians (median age: 32 yrs, 67.6% female) from 11 skin cancer centers were surveyed to rate typical side effect scenarios of (c)ICI and TT treatments and then compared to patients’ ratings evaluated in a previous analysis from the same centers. The scenarios described mild-to-moderate or severe toxicity and included melanoma relapse leading to death. The physicians were asked about the level of side effects they would tolerate in exchange for a reduction in melanoma relapse and an increase in survival at 5 years.ResultsThe preferences of physicians and patients revealed significant differences regarding adjuvant melanoma treatment with (c)ICI and TT (p < 0.05). Compared to patients, physicians tend to value a melanoma relapse less severe, according to a visual analog scale. They were also less threatened by all scenarios of side effects during adjuvant treatment with (c)ICI or TT, compared to patients. Physicians required lower risk reductions for disease-free survival (DFS) and overall survival (OS) for both ICI and TT and their drug-related side effects to accept these treatments. In case of severe side effects, physicians required similar 5-year DFS rates for ICI and TT (60–65%), while patients needed a 15% improvement of 5-year DFS for ICI compared to TT (80%/65%). For survival, physicians expected an OS improvement of + 10% for all three treatment modalities, whereas patients required a higher increase: + 18–22% for ICI and + 15% for TT.ConclusionOur study highlights the importance of understanding the patient’s perspective and a potential difference to the doctor’s view when making decisions about adjuvant melanoma treatment with (c)ICI and TT, especially as these treatments are increasingly being implemented in earlier stages.

Abstract PO1-17-08: Post-approval treatment patterns and tolerability of neratinib in HER2+ early-stage breast cancer

Abstract Background: While the approval status for neratinib in HER2+ early-stage breast cancer (EBC) allows its use following any trastuzumab-based therapy, the phase 3 ExteNET trial (NCT00878709), which yielded an improvement in disease-free survival, was conducted when single-agent adjuvant trastuzumab was standard of care (SOC) and before approvals of adjuvant pertuzumab + trastuzumab (FDA-approved 2017) or trastuzumab emtansine (T-DM1; FDA-approved 2019). Given recent changes in SOC for HER2+ EBC, health care professionals may seek contemporary and real-world information regarding treatment patterns and tolerability of neratinib. Methods: A literature review was performed to identify studies that characterized trends in use of extended adjuvant neratinib in HER2+ EBC. Due to differences in study design (interventional, observational, claims data) and populations studied, a descriptive summary of data is presented in lieu of statistical cross-study comparisons. Results: Following FDA approval of neratinib in HER2+ EBC in 2017, five studies have reported treatment patterns of extended adjuvant neratinib in a clinical trial or real-world setting; three studies included safety data (Table 1). In the phase 2 CONTROL trial (NCT02400476; N=563; 2015–2021), approx. 82%, 17%, and 1% of neratinib-treated pts received prior adjuvant trastuzumab, pertuzumab, or T-DM1, respectively, and prior neoadjuvant/adjuvant pertuzumab did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration.1 In an interim analysis of the observational ELEANOR study (NCT04388384; N=187; 2020–ongoing), approx. 41%, 33%, and 19% of neratinib-treated pts received prior adjuvant trastuzumab (as their only anti-HER2 treatment), pertuzumab + trastuzumab, or T-DM1, respectively; corresponding rates of grade ≥3 diarrhea were 19%, 25%, and 14%, respectively, with no new safety signals reported.2 In a chart review from the US Oncology Network (N=166; 2017–2020), approx. 99%, 43%, and 2% of neratinib-treated pts received prior adjuvant trastuzumab (56% as their sole anti-HER2 treatment), pertuzumab, or T-DM1, respectively.3 Diarrhea was mainly moderate (29%; n=43/150) or mild (22%; n=33/150), with few severe cases (1%; n=2/150).3 In a retrospective analysis employing the IQVIA claims database (N=385; 2017–2021), prior use of recently approved adjuvant agents increased over time, with rates of prior pertuzumab + trastuzumab or prior T-DM1 as high as 52% and 14%, respectively, in 2020.4 In the Neat-HER virtual registry (N=46; 2018–2021), approx. 41% and 11% of neratinib-treated pts received prior adjuvant pertuzumab or T-DM1, respectively.5 Conclusions: Recent studies have observed neratinib use in clinical practice following adjuvant trastuzumab-based therapy including pertuzumab + trastuzumab or T-DM1. Preliminary data suggest a similar safety profile for pts with/without prior pertuzumab. These datasets are limited by the fact that: (1) some pts were enrolled in the CONTROL trial prior to launch of adjuvant T-DM1 and pertuzumab; (2) the interval between T-DM1 launch in Europe and start of the ELEANOR study was relatively short; and (3) not all toxicity measures were formally graded. A summary of available safety and effectiveness results is forthcoming. Additional interventional and non-interventional studies will continue to evaluate the safety and effectiveness of neratinib following current SOC adjuvant therapy in HER2+ EBC. Table 1. Treatment patterns of HER2-targeted adjuvant agents preceding neratinib use in HER2+ EBC ITT, intent-to-treat; T-DM1, ado-trastuzumab emtansine. aTherapies were recorded as used for adjuvant therapy in CONTROL, ELEANOR, US Oncology, and Neat-HER. CONTROL includes unpublished data. In the IQVIA claims analysis, HER2-targeted agent(s) used within 12 months prior to neratinib initiation were assumed to be adjuvant therapies. Pertuzumab use was generally taken in combination with trastuzumab as dual HER2 blockade and some pts received more than one anti-HER2 adjuvant treatment, for example T-DM1 in addition to pertuzumab plus trastuzumab. bAdjuvant trastuzumab monotherapy or in combination with chemotherapy unless noted otherwise. cThe proportion of patients who took at least one tablet of neratinib for ≥75% of the prescribed treatment days and did not take neratinib on days when neratinib was not prescribed. dData forthcoming. eIncludes prior trastuzumab monotherapy and trastuzumab used in combination with pertuzumab; 93/166 pts (56%) received trastuzumab as their only anti-HER2 agent (monotherapy or in combination with chemotherapy; unpublished data). fIncludes prior trastuzumab monotherapy as well as trastuzumab used in combination with pertuzumab. References Citation Format: Kelly McCann, Nadia Harbeck, Debu Tripathy, Arlene Chan, Jay Andersen, Joyce O'Shaughnessy, Gregory Vidal. Post-approval treatment patterns and tolerability of neratinib in HER2+ early-stage breast cancer [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 PO1-17-08.

Abstract Db1-01: Anthracyclines …to give or not to give? “For” argument

Abstract Anthracyclines have been one of the mainstays of early breast cancer treatment for decades. In a recent patient-level meta-analysis including data from over 18,000 patients, anthracycline-containing regimens were associated with improvements in disease-free survival and overall survival, regardless of estrogen receptor or nodal status. Importantly, trials specifically designed and powered to assess the safety of anthracyclines omission failed to demonstrate the non-inferiority of taxane-based anthracycline-free regimens and confirmed the benefit of these agents, particularly in patients with node-positive and hormone receptor-negative breast cancer. Several therapies incorporated into the management of early breast cancer were studied in populations largely treated with anthracycline-based chemotherapy backbones in both HER2-negative (i.e., perioperative pembrolizumab, post neoadjuvant olaparib and capecitabine) and HER2-positive disease (i.e., dual HER2 blockade, adjuvant T-DM1). It is uncertain whether the benefits demonstrated by these strategies would be maintained if anthracyclines were omitted. While anthracyclines are associated with some long-term toxicities, particularly with an increased risk of lymphoproliferative malignancies and dose-dependent cardiotoxicity, these adverse events are not associated with an increased risk of death (including deaths from cardiovascular causes) when compared to anthracycline-free regimens. The identification of risk factors for cardiotoxicity, combined with improvements in monitoring strategies, allows improvements in patient selection, early detection of myocardial damage and, possibly, implementation of cardioprotective interventions, leading to improved cardiovascular outcomes. Until high-quality evidence demonstrates the safety of omitting anthracyclines in high-risk populations, these agents should continue to be used in carefully selected patients after individual risk versus benefit assessment to be shared with the patient. Citation Format: Martine Piccart, Guilherme Nader-Marta. Anthracyclines …to give or not to give? “For” argument [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 Db1-01.

Patients' Preferences for Adjuvant Osimertinib in Non–Small-Cell Lung Cancer After Complete Surgical Resection: What Makes It Worth It to Patients?

BackgroundThe ADAURA trial confirmed adjuvant Osimertinib's efficacy in EGFR-mutated Non–small-cell lung cancer (NSCLC), yet the limited mature overall survival (OS) data at approval poses a challenge. This study explores patient preferences in the absence of complete OS information, hypothesizing that disease-free survival (DFS) benefit alone may influence adjuvant Osimertinib pursuit. MethodsAt Roswell Park Comprehensive Cancer Center (Jan-Dec 2021), patients assessed for adjuvant therapy received a survey probing OS and DFS preferences. Scenarios were (a) minimum OS justifying Osimertinib, (b) minimum DFS improvement justifying 3-years of adjuvant Osimertinib, (c) minimum 5-year DFS percent change, and (d) minimum OS justifying copay changes. Results were analyzed. ResultsOf 524 NSCLC patients, 51 participated. Scenario 1 saw 56% requiring a 12-month OS benefit for Osimertinib justification. In scenario 2, 72% deemed a 12-month DFS benefit sufficient. Scenario 3 revealed 31% opting out despite a 10% OS increase. Scenario 4 showed varied willingness to pay, with 33% unwilling to any shoulder copayment even with a 10-year OS benefit. ConclusionThis study explores patient preferences without complete OS data, revealing diverse thresholds. Factors include employment, education, and willingness to pay. Findings underscore shared decision-making importance. Limitations include sample size, potential biases, and regional focus; larger cohorts are needed for validation.

Abstract CT239: IMpower010: Updated overall survival and safety results from Asian patients in a Phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA NSCLC

Abstract Background The Phase III IMpower010 study (NCT02486718) met its primary endpoint at the disease-free survival (DFS) interim analysis (IA; clinical cutoff: Jan 21, 2021), demonstrating significant DFS improvement with atezolizumab (atezo) vs best supportive care (BSC) after adjuvant chemotherapy (chemo) in patients with resected stage II-IIIA NSCLC, including those with PD-L1 TC ≥1%. Based on these findings, atezo was approved as adjuvant therapy after platinum-based chemo in patients with completely resected PD-L1 TC ≥1% stage II-IIIA NSCLC in the US, China and other countries, and in patients with completely resected PD-L1 TC ≥50% stage II-IIIA NSCLC in the EU and other countries. In a previous exploratory analysis at the time of the DFS IA, the IMpower010 Asian subpopulation showed efficacy and safety outcomes that were consistent with those of the global population (Kenmotsu et al. JSMO 2021). Here we report updated data from the IMpower010 Asian subpopulation at the first overall survival (OS) IA. Methods The IMpower010 study design and DFS IA have been previously reported (Felip et al. Lancet 2021). Eligible patients with completely resected stage IB (≥4 cm)-IIIA NSCLC (AJCC/UICC v7) received one to four 21-day cycles of cisplatin-based doublet chemo and were subsequently randomized 1:1 to receive atezo 1200 mg q3w (16 cycles) or BSC. The first pre-specified OS IA was conducted at the clinical cutoff date of Apr 18, 2022. OS in the intention-to-treat (ITT) population will be formally tested if DFS in the ITT population reaches statistical significance at the final DFS analysis. Exploratory OS and updated safety outcomes were evaluated in the Asian subpopulation. Results The Asian ITT population included 233 patients recruited from Japan, mainland China, Taiwan, Korea and Hong Kong. At data cutoff (Apr 18, 2022), the unstratified OS HR was 0.73 (95% CI: 0.28, 1.88) in favor of atezo in the PD-L1 TC ≥1% (SP263) stage II-IIIA population (n=129). The Asian safety-evaluable population included 229 patients (atezo, n=122; BSC, n=107). Any-grade adverse events (AEs) were reported in 95.1% (atezo) and 72.0% (BSC) of safety-evaluable patients; events were Grade 3/4 in 24.6% and 13.1%, respectively. Grade 5 treatment-related AEs occurred in 1 patient in the atezo arm. AEs leading to atezo discontinuation occurred in 21.3% of patients treated with atezo. Conclusions The IMpower010 Asian subpopulation showed an OS trend favoring atezo vs BSC in the PD-L1 TC ≥1% stage II-IIIA population, as was observed in the global population, although OS data were not formally tested in either population at the first OS IA. With longer follow-up, the safety findings for atezo in the IMpower010 Asian subpopulation remained broadly unchanged, were consistent with those of the global IMpower010 population and were in line with the known safety profile of atezo. Medical writing support for this abstract was provided by Kia C. E. Walcott, PhD, of Nucleus Global, an Inizio Company, and funded by F. Hoffmann-La Roche, Ltd. Citation Format: Jie Wang, Yun Fan, Jian Fang, Jianxing He, Yunpeng Liu, Min Tao, Nasser Altorki, Enriqueta Felip, Heather Wakelee, Eric Vallieres, Rossella Belleli, Virginia McNally, Elizabeth Bennett, Barbara J. Gitlitz, Caicun Zhou. IMpower010: Updated overall survival and safety results from Asian patients in a Phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT239.

Neoadjuvant Chemotherapy in Patients with HER2-Negative Breast Cancer: A Report from Clinical Breast Cancer Registry of Iran.

Neoadjuvant chemotherapy (NCT) has become an increasingly popular approach in management of breast cancer (BC). This study was conducted to evaluate the pathologic response and 36-month recurrence and survival rates of patients with human epidermal growth factor receptor 2 (HER2)-negative BC treated with different NCT regimens. A total of 163 female patients with HER2-negative BC who received NCT during 2017-2020 were identified from the Clinical Breast Cancer Registry of Iran and entered the study. The prescribed NCT regimens included 4 cycles of doxorubicin plus cyclophosphamide, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of paclitaxel, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of docetaxel or 6 cycles of doxorubicin plus cyclophosphamide plus docetaxel (TAC). Thirty-two patients (19.6%) experienced pathologic complete response (pCR). TAC regimen, triple negative-BC and ki67>10% were significantly associated with increased pCR. The recurrence, overall survival (OS) and disease-free survival (DFS) rate at 36 months for all patients were 16.6%, 84.7% and 79.8%, respectively. Type of neoadjuvant regimen as well as age, hormone receptor status, Ki67, grade, clinical stage, type of surgery and pathologic response to chemotherapy did not significantly influence the survival and recurrence; however, TAC results in improved recurrence, OS and DFS rates. This study provides further evidence that NCT is a viable treatment option for patients with HER2-negative BC. The TAC regimen resulted in a significantly higher pCR rate compared to other regimens, but did not result in a significant improvement in recurrence, OS and DFS and rates.