Pembrolizumab with or without chemotherapy versus chemotherapy alone for patients with PD-L1–positive advanced gastric or gastroesophageal junction adenocarcinoma: Update from the phase 3 KEYNOTE-062 trial.
Zev A. Wainberg, Kohei Shitara, Eric Van Cutsem, Lucjan Wyrwicz, Keun Wook Lee, Iveta Kudaba, Marcelo Garrido, Hyun Cheol Chung, Jeeyun Lee, Hugo Castro‐Salguero, Wasat Mansoor, Maria Ignez Braghiroli, Nina Karaseva, Eray Goekkurt, Hironaga Satake, Joseph Chao, Uma Kher, Sukrut Shah, Pooja Bhagia, Josep Tabernero
Abstract
243 Background: KEYNOTE-062 (NCT02494583) is a global phase 3 study of pembrolizumab (pembro) as monotherapy and in combination with chemotherapy (chemo) versus chemo as first-line therapy for PD-L1–positive (combined positive score [CPS] ≥1) advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. At the time of the protocol-specified final analysis, pembro was noninferior to chemo, with fewer adverse events (AEs) observed. Pembro or pembro + chemo was not superior to chemo for the overall survival (OS) and progression-free survival (PFS) end points tested. We present the results of KEYNOTE-062 after ̃25 additional months of follow-up (cutoff: April 19, 2021). Methods: Patients with previously untreated gastric or GEJ cancer were randomly assigned 1:1:1 to pembro 200 mg Q3W, pembro + chemo (cisplatin 80 mg/m 2 /day on day 1 + 5-FU 800 mg/m 2 /day on days 1-5 Q3W [or capecitabine 1000 mg/m 2 twice daily on days 1-14 Q3W per local guidelines]), or placebo Q3W + chemo. Primary end points were OS in the CPS ≥1 and CPS ≥10 populations for pembro + chemo versus chemo and pembro versus chemo and PFS (RECIST v1.1; central review) in the CPS ≥1 and CPS ≥10 populations for pembro + chemo versus chemo. Safety was also evaluated. Results: At the time of data cutoff, 689 of 763 patients (90.3%) had died. Median follow-up (defined as time from randomization to data cutoff) was 54.3 months (range, 46.8-66.1). Pembro was noninferior to chemo for OS in the CPS ≥1 population (median, 10.6 vs 11.1 months; HR, 0.90; 95% CI, 0.75-1.08) but had a clinically meaningful OS benefit in the CPS ≥10 population (median, 17.4 vs 10.8 months; HR, 0.62; 95% CI, 0.45-0.86). 24-month OS rates (pembro vs chemo) were 26.6% versus 18.8% in the CPS ≥1 population and 39.1% versus 21.1% in the CPS ≥10 population. Pembro + chemo was not superior to chemo for OS in the CPS ≥1 (median, 12.5 vs 11.1 months; HR, 0.85; 95% CI, 0.71-1.02) or the CPS ≥10 (median, 12.3 vs 10.8 months; HR, 0.76; 95% CI, 0.56-1.03) population. 24-month OS rates (pembro + chemo vs chemo) were 24.5% versus 18.8% in the CPS ≥1 population and 28.3% versus 21.1% in the CPS ≥10 population. Pembro + chemo did not significantly prolong PFS versus chemo in the CPS ≥1 (median, 6.9 vs 6.5 months; HR, 0.84; 95% CI, 0.70-1.01) or the CPS ≥10 (median, 5.8 vs 6.2 months; HR, 0.71; 95% CI, 0.52-0.96) population. Grade 3-5 treatment-related AEs rates were 17.3% (pembro), 73.2% (pembro + chemo), and 69.3% (chemo). Conclusions: After ̃25 additional months of follow-up, efficacy and safety outcomes with first-line pembro or pembro + chemo versus chemo in patients with gastric or GEJ adenocarcinoma enrolled in KEYNOTE-062 were consistent with the final analysis data. Clinical trial information: NCT02494583.