US-based pharma major MSD (tradename of Merck & Co., Inc) announced that the Drugs Controller General of India (DCGI) has approved its anti cancer drug Keytruda (pembrolizumab), for additional indications of cervical cancer and esophageal cancer. The company said that the anti-programmed death receptor-1 (PD-1), has received approval for the treatment of persistent, recurrent, or metastatic cervical cancer in adults whose tumours express PD-L1 with a CPS =1, and for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the esophagus or HER-2 negative gastroesophageal junction adenocarcinoma, in adults whose tumours express PD-L1 with a CPS = 10.

Merck...today announced that the European Commission (EC) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with platinum- and fluoropyrimidine-based chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the esophagus or human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10).

Merck...announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with platinum- and fluoropyrimidine-based chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the esophagus...The positive CHMP opinion is based on results from the pivotal Phase 3 KEYNOTE-590 trial...

Of 749 patients enrolled...88.7% were male and 49.1% had PD-L1 CPS ≥10...Additionally, in Chinese patients (pembrolizumab + chemotherapy vs chemotherapy), median OS was 10.5 months versus 8.0 months (HR, 0.51; 95% CI, 0.32-0.81), median PFS was 6.2 months versus 4.6 months (HR, 0.60; 95% CI, 0.39-0.92), ORR was 37.3% versus 20.0%, and median DOR (range) was 6.4 months (2.2+ to 18.9+) versus 4.0 months (1.5+ to 16.6+).

In this open-label, phase III study, we randomly assigned (1:1) 628 patients with advanced/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, that progressed after one prior therapy, to pembrolizumab...OS was prolonged with pembrolizumab versus chemotherapy for patients with CPS ≥ 10 (median, 9.3 v 6.7 months; hazard ratio [HR], 0.69 [95% CI, 0.52 to 0.93]; P = .0074)....Pembrolizumab prolonged OS versus chemotherapy as second-line therapy for advanced esophageal cancer in patients with PD-L1 CPS ≥ 10...

...pts with ESCC PD-L1 combined positive score (CPS) ≥10 tumors...Pembro + chemo provided superior OS, PFS, and ORR vs chemo, with a manageable safety profile in pts with untreated, advanced esophageal and EGJ cancer.

...- Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with known programmed cell death ligand 1 (PD-L1) expression status...

...Improved 1 Year Survival`Induction of PD-L1 Expression or Induction of an Inflammatory Signature in Tumors.`...

...Note: All participants in Cohort 3 had a PD-L1-positive tumor status.`...

...Programmed cell death ligand 1 (PD-L1) expression in tumor cells...

...- Has PD-L1 positive tumor (based on analysis of sample provided to core lab)....

...As of 20 March 2016, participants must be PD-L1 positive to be enrolled....

...- Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with known programmed cell death ligand 1 (PD-L1) expression status...

...PD-L1 expression status in tissue samples collected at baseline before receiving any prior systemic anticancer therapy are of highest interest....

...PD-L1 expression is measured by 22C3 clone PD-L1 IHC assay followed by combined positive score (CPS) scoring methods.`...

...- Patients must have analysis of PD-L1 expression in cancer cells quantitated by immunohistochemistry analysis....

In all patients at month 33, patients receiving pembrolizumab + chemotherapy had a 1.51 month (95% CI, 0.10-2.95) longer restricted mean time in TWiST...In patients with PD-L1 CPS 10, those receiving pembrolizumab + chemotherapy had a 2.24 month (95% CI, 0.08-4.44) longer restricted mean time in TWiST (6.35 vs 4.11 months)...Pembrolizumab + chemotherapy demonstrated clinically meaningful improvement in quality-adjusted survival based on Q-TWIST analyses compared with chemotherapy in patients with advanced esophageal cancer.

The KEYNOTE-180 trial (NCT02559687) was a single-arm phase 2 study of pembrolizumab as third-line or greater therapy in advanced/metastatic esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma (SCC). Median OS was slightly higher among patients with SCC in the GEPnon-low subgroup and the CPS ≥10 subgroup versus GEPlow and CPS <10 subgroups, respectively (tables 1, 2); this trend was reversed among patients with adenocarcinoma (tables 1, 2). Median PFS ranged from 1.9 to 2.1 across histology/biomarker subgroups. Median DOR was NR regardless of GEP or CPS status (tables 1, 2).

Overall response rate was 30% (95% CI, 13% to 53%); median duration of response was 15 months (range, 6 to 26 months)....Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1–positive advanced esophageal carcinoma.