KEYNOTE-063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second-line therapy in Asian patients with advanced programmed death ligand 1 (PD-L1)-positive (combined positive score ≥1) gastric/gastroesophageal junction (GEJ) cancer….Median OS was 8 months (95% confidence interval [CI], 4-10 months) with pembrolizumab versus 8 months (95% CI, 5-11 months) with paclitaxel (hazard ratio [HR], 0.99; 95% CI, 0.63-1.54).

Pembrolizumab demonstrated a trend toward improved OS vs paclitaxel in the CPS ≥ 1 population (HR, 0.81); 24-month OS rates: 19.9% vs 8.5%....In this long-term analysis, 2L pembrolizumab did not significantly improve OS but was associated with higher 24-month OS rates than paclitaxel. Pembrolizumab also increased OS benefit with PD-L1 enrichment among patients with PD-L1-positive gastric/GEJ cancer and led to fewer TRAEs than paclitaxel.

NON-SUPPORTIVE EVIDENCE:...pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of 1 or greater (median, 10.6 vs 11.1 months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1.18). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of 1 or greater.

Among patients with PD-L1–positive advanced gastric/GEJ cancer, OS on subsequent therapy was better in the pembrolizumab group than the paclitaxel group, with a possibly greater effect when an anti-VEGF plus taxane was given as subsequent therapy.

Pembrolizumab prolonged OS vs paclitaxel in PD-L1–positive patients (Table). No significant differences appeared between groups in PFS (Table). Objective response rate (ORR) was higher for pembrolizumab in the CPS ≥10 group, and DOR was longer with pembrolizumab using all CPS cutoffs (Table).

...patients with a programmed cell death ligand 1 (PD-L1)...Median overall survival was 9·1 months (95% CI 6·2-10·7) with pembrolizumab and 8·3 months (7·6-9·0) with paclitaxel (hazard ratio [HR] 0·82, 95% CI 0·66-1·03; one-sided p=0·0421)...Median progression-free survival was 1·5 months (95% CI 1·4-2·0) with pembrolizumab and 4·1 months (3·1-4·2) with paclitaxel (HR 1·27, 95% CI 1·03-1·57)...Pembrolizumab had a better safety profile than paclitaxel.

Eligible patients were randomized in a 1:1 ratio to pembrolizumab 200 mg Q3W or paclitaxel 80 mg/m2....In post-hoc analysis, the pembrolizumab treatment effect for OS was also greater in patients with CPS ≥10 (median OS 10.4 mo vs 8.0 mo; HR 0.64, 95% CI 0.41-1.02) and in patients with MSI-H tumors.

Keytruda as monotherapy is indicated for the first line treatment of metastatic non small cell lung carcinoma in adults whose tumours express PD L1 with a ≥ 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations.

Willing to provide tissue for PD-L1 biomarker analysis from newly-obtained and/or archival tissue...

...Human epidermal growth factor receptor 2- (HER2/neu-) negative and programmed cell death ligand 1 (PD-L1)-positive...

Of the 33 patients, 12 were MSI-H, 3 EBV (+), and 27 had PDL1 expression with CPS >/= 1%. Tumors were of advanced clinical stage with 84.8% ≥ cT3 and 57.6% cN(+). All patients received two cycles of neoadjuvant pembrolizumab...treatment effect was seen in 46%, down-staging in 50%, and complete pathologic response seen in 3 patients, 2 of whom has MSI-H tumors and one whose tumor was PDL1+...This study presents a novel and effective paradigm for the management of localized gastric cancer...

Eligible patients were randomly assigned 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin + 5-fluorouracil or capecitabine)...In the programmed death ligand 1 combined positive score ≥10 population, median overall survival was also numerically longer with pembrolizumab versus chemotherapy (28.5 vs 14.8 months; hazard ratio, 0.43; 95% confidence interval, 0.21-0.89)...pembrolizumab monotherapy was associated with numerically improved overall survival and a favourable tolerability profile versus chemotherapy in Asians with programmed death ligand 1-positive advanced gastric cancer/gastrooesophageal junction cancer.

"...pembrolizumab monotherapy given as first-line (KEYNOTE-062), second-line (KEYNOTE061), and third-line and later (KEYNOTE-059) therapy showed a clinically meaningful median and long-term survival benefit in patients with CPS ≥ 10 gastric or GEJ tumors and more durable responses compared with chemotherapy."

This study showed the encouraging efficacy and manageable safety of SOX with P therapy as a first line in pts with HER2-negative, PD-L1-positive AGC.

In study 059, 46 pts in cohort 1 with PD-L1 CPS ≥10 received pembro. In study 061, 108 pts with PD-L1 CPS ≥10 received pembro (n=53) or chemotherapy (chemo; n=55)...Collectively, these data indicate that 1L, 2L, and 3L+ pembro monotherapy showed clinically meaningful efficacy in CPS ≥10, with a more durable response than chemotherapy.

Pembro prolonged OS vs chemo in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97)…

Objective response rate and median (range) response duration were 15.5% (95% CI, 10.1%-22.4%; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4% (95% CI, 2.6%-12.8%; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1-positive and PD-L1-negative tumors, respectively.