<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%) –
Supplementary Data from Putative Biomarkers of Clinical Benefit With Pembrolizumab in Advanced Urothelial Cancer: Results from the KEYNOTE-045 and KEYNOTE-052 Landmark Trials
Posterior reversible encephalopathy syndrome is an entity with signs and neurological symptoms hypothetically triggered by a vasogenic edema or endothelial dysfunction. Children debut clinically with headache, visual impairment, altered consciousness and epileptic seizures. This review shows a series of six patients with PRES associated with various pathologies. The cause may be secondary to the underlying pathology by one of the three different theories of the disease which are hypertension / hyperfunction, dysfunction in vasogenic self-regulation and endothelial dysfunction. In our sample, the female sex and school stage predominate as shown in other case reports. Objective: Describe the presence of reversible posterior encephalopathy syndrome associated with various pathologies.
Patients with melanoma and early stable disease (SD) with pembrolizumab have unclear prognosis. We present post hoc analyses of long-term outcomes for patients with early SD, partial response (PR) or complete response (CR) with pembrolizumab.Patients who received pembrolizumab in the KEYNOTE-001 and KEYNOTE-006 studies and had SD, PR or CR at weeks 12 or 24 were included.Of 294 patients in the week 12 analysis, 107 (36.4%) had SD at week 12, of whom 7 (6.5%) had a best overall response of CR, 43 (40.2%) had PR and 57 (53.3%) had SD. Forty-eight-month overall survival (OS) rates were 95.2%, 73.0% and 47.7%, respectively, for patients with CR, PR and SD at week 12. Similar results were observed in the 241 patients in the week 24 analysis. Forty-eight-month OS rates were 72.1% for patients with SD at week 12 followed by subsequent response and 75.0% for patients with PR at week 12 followed by no change in response or progression. Thirty-six-month and 48-month OS rates were 11.6% and not reached, respectively, for patients with SD at week 12 followed by progression before week 24.A substantial proportion of patients (46.7%) with early (week 12) SD with pembrolizumab achieved subsequent PR or CR. Patients with SD at week 12 and subsequent CR/PR had similar survival to those who maintained PR. In contrast, patients with SD at week 12 and subsequent progression had poor survival outcomes. These findings may guide treatment decisions for patients achieving early SD.Clinicaltrials.gov: NCT01295827 (KEYNOTE-001); NCT01866319 (KEYNOTE-006).
Abstract Background First‐line pembrolizumab monotherapy is a standard of care for platinum‐ineligible patients with advanced urothelial carcinoma (UC). No global standardized definition of platinum ineligibility exists. This study aimed to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with UC who met various criteria for platinum ineligibility. Methods Patients from KEYNOTE‐052 and LEAP‐011 deemed potentially platinum ineligible were pooled for this post hoc exploratory analysis as follows: group 1: Eastern Cooperative Oncology Group performance status (ECOG PS) 2; group 2: ECOG PS 2 and age ≥80 years, renal dysfunction, or visceral disease; and group 3: any two other factors regardless of ECOG PS. Patients received pembrolizumab 200 mg intravenously every 3 weeks. End points included objective response rate (ORR), progression‐free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1, by blinded independent central review, overall survival (OS), and safety. Results A total of 612 patients treated with pembrolizumab from KEYNOTE‐052 ( n = 370) and LEAP‐011 ( n = 242) were included; the median (range) follow‐up was 56.3 months (51.2–65.3 months) and 12.8 months (0.2–25.1 months), respectively. For group 1, ORR was 26.2%, median PFS was 2.7 months, and median OS was 10.1 months. For group 2, ORR ranged from 23.5% to 33.3%, median PFS ranged from 2.1 to 4.4 months, and median OS ranged from 9.1 to 10.1 months. For group 3, ORR ranged from 25.7% to 27.9%, median PFS ranged from 2.1 to 2.8 months, and median OS ranged from 9.0 to 10.6 months. Treatment‐related adverse event rates were consistent across groups. Conclusions Frontline pembrolizumab has consistent antitumor activity and safety in patients with advanced UC categorized as potentially ineligible for platinum‐based chemotherapy, regardless of the variable definitions of platinum ineligibility used.
