<p>Supplementary Figure 4. Kaplan-Meier estimates of survival by dual TMB and PD-L1 CPS cutoffs for pembrolizumab plus chemotherapy versus chemotherapy. <b>A</b>, PFS. <b>B,</b> OS.</p>
664 Background: EV-302 /KEYNOTE-A39 (NCT04223856) demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit with first-line (1L) EV+P vs chemo in patients (pts) with la/mUC. EV+P is the standard of care (SOC) in global treatment guidelines for pts with untreated la/mUC. We present 12 mo of additional follow-up for EV-302 (>2 y of median follow-up) and an exploratory analysis of pts with confirmed complete response (cCR). Methods: Pts with previously untreated la/mUC were randomized 1:1 to receive EV (1.25 mg/kg; Days 1 and 8; IV) and P (200 mg; Day 1; IV) or gemcitabine with cisplatin or carboplatin every 3 wks. Dual primary endpoints were PFS by blinded independent central review (BICR) and OS. Select secondary endpoints were confirmed objective response rate (cORR), duration of response (DOR), and safety. An exploratory analysis evaluated treatment outcomes and safety in pts with cCR. Results: 886 pts were randomized to receive EV+P (n=442) or chemo (n=444). At data cutoff (Aug 8, 2024), median follow-up was 29.1 mo (95% CI, 28.5-29.9). PFS by BICR (HR, 0.48 [95% CI, 0.41-0.57]) and OS (HR, 0.51 [95% CI, 0.43-0.61]) were improved in the EV+P vs chemo arms (Table). OS benefit was seen irrespective of cisplatin eligibility or presence of liver metastases (mets). In the response-evaluable set, cORR was 67.5% for EV+P and 44.2% for chemo. Median DOR was 23.3 mo (95% CI, 17.8-not estimable [NE]) for EV+P and 7.0 mo (95% CI, 6.2-9.0) for chemo. 30.4% of pts in the EV+P arm and 14.5% in the chemo arm achieved cCR. Median duration of cCR was not reached for EV+P and 15.2 mo (95% CI, 10.3-NE) for chemo. Grade ≥3 treatment-related (TR) adverse events (AEs) in the EV+P vs chemo arms occurred in 57.3% vs 69.5% of pts in the safety analysis set (Table) and 61.7% vs 71.9% of pts in the cCR subgroup, respectively. TR deaths occurred in 1.1% vs 0.9% of pts in the safety analysis set in the EV+P vs chemo arms, respectively; none occurred in the cCR subgroup. Conclusions: EV+P continues to demonstrate superior efficacy vs chemo in a broad population, consistent with the primary analysis. Results confirm durable EV+P efficacy with no new safety signals, reinforcing EV+P as SOC for the 1L treatment of pts with la/mUC. Clinical trial information: NCT04223856 . Key efficacy and safety outcomes. EV+P Chemo EV+P vs chemo Efficacy (intent to treat set) n mo n mo HR (95% CI) Median PFS 442 12.5 (95% CI, 10.4-16.6) 444 6.3 (95% CI, 6.2-6.5) 0.48 (0.41-0.57) Median OS 442 33.8 (95% CI, 26.1-39.3) 444 15.9 (95% CI, 13.6-18.3) 0.51 (0.43-0.61) Cisplatin eligible 244 36.7 234 18.7 0.54 (0.42-0.70) Cisplatin ineligible 198 25.6 210 12.7 0.50 (0.39-0.64) Liver mets present 100 19.1 99 10.1 0.56 (0.40-0.78) Liver mets absent 342 39.3 345 18.3 0.50 (0.40-0.62) Safety (safety analysis set) n n Grade ≥3 TRAE 440 252 (57.3%) 433 301 (69.5%) –
<p>Supplementary Figure 1: Correlation betweenSARS-CoV-2 anti-S1 IgG antibody titers and NT50 values against Wuhan and BA.1 Omicron strains post homologous or heterologous booster vaccination in cancer patients and healthy individuals.</p>
The aim of this study is to assess baseline mean leukocyte telomere length (TL) as a potential predictive factor for chemotherapy toxicity and a prognostic marker for long-term outcome in early breast cancer (BC) patients.445 BC patients were selected, diagnosed between 2007 and 2010 with early BC and treated with (neo)adjuvant fluorouracil, epirubicin and cyclophosphamide (FEC) or with FEC and Docetaxel (FEC-D). RT-qPCR was performed on germline DNA samples collected at diagnosis before any treatment, to measure mean leukocyte TL. Uni- and multivariable logistic regression or Cox proportional hazard regression analyses were carried out to assess correlation between baseline TL and toxicity parameters (derived from the medical chart) or longer-term outcome.Baseline TL correlated with age as expected (p = 0.005), but not with febrile neutropenia (n = 97), left ventricular ejection fraction >10% decrease (n = 17) nor other toxicity endpoints measured (all p > 0.05). TL was neither associated with overall survival, breast cancer specific survival or distant disease-free survival (all p > 0.05).Baseline TL is not associated with chemotherapy-related toxicity nor long-term outcome in BC patients.
