KEY TAKEAWAYS
- The MK-3475-811/KEYNOTE-811 phase III trial aimed to update previous findings on PFS in a targeted patient group.
- The dual primary endpoints were PFS or OS.
- The result demonstrated that adding pembrolizumab to standard treatment in HER2+ mG/GEJ cancer significantly prolonged PFS and response rates, especially for those with elevated PD-L1 levels.
Pembrolizumab (pembro)/trastuzumab combined with chemotherapy(chemo) demonstrated a higher overall response rate (ORR) of 74% compared to placebo (pbo)/trastuzumab with chemo at 52% in the initial 264 patients. These findings led to the FDA approval of first-line pembro/trastuzumab with chemo for HER2+ metastatic or gastroesophageal junction.
For this study, researchers aimed to provide an update on the previous findings on PFS in a targeted patient group.
Patients aged 18 years or older with untreated, unresectable HER2+ metastatic or gastroesophageal junction adenocarcinoma, regardless of PD-L1 status, were randomly assigned in a 1:1 ratio.
The randomization included pembro at 200 mg IV every 3 weeks or pbo IV every 3 weeks, combined with chemo (5-FU and cisplatin [FP] or capecitabine and oxaliplatin [CAPOX] and trastuzumab [SOC]).
Stratification factors included region, PD-L1 status, and choice of chemotherapy. Treatment duration was up to 2 years or until disease progression or intolerable toxicity.
The dual primary endpoints were progression-free survival (PFS) and overall survival (OS) assessed per RECIST v1.1 (BICR). The interim analysis cut-off date was May 25, 2022, with ongoing OS assessment per the Data and Safety Monitoring Committee (DSMC) recommendation.
About 698 patients were randomized (350 to pembro + SOC; 348 to pbo + SOC). With a median follow-up of 28.4 months, pembro + SOC significantly improved PFS compared to placebo + SOC in all patients (median 10.0 vs 8.1 months; HR 0.72; 95% CI 0.60-0.87; P=0.0002).
The median (range) duration of response was 11.2 months (1.1+ to 40.1+) vs 9.0 months (1.4+ to 38.3+). Approximately 31% vs 19% of responders had a response duration ≥24 months. Grade ≥3 drug-related adverse event rates were 58% vs 51%. Grade 5 drug-related adverse events occurred in 4 (1.1%) vs 3 (0.9%) patients, respectively.
The result demonstrated that adding pembro to standard treatment in HER2+ mG/GEJ cancer significantly prolonged PFS and response rates, especially for those with elevated PD-L1 levels.
Clinical Trial: https://clinicaltrials.gov/study/NCT03615326
Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges J, Yanez Weber PE, Wyrwicz LS, Shen L, Ostapenko YV, Bilici M, Chung HC, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li K, Shih C, Bhagia P, Rha SY. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Survival results from the phase III, randomized, double-blind, placebo-controlled KEYNOTE-811 study. Ann Oncol. 2023;34(suppl_2):S852-S886. doi:10.1016/annonc/annonc1318.
