Bristol Myers Squibb...announced that the European Commission (EC) has approved Opdivo (nivolumab) in combination with fluoropyrimidine- and platinum-based chemotherapy for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) with tumor cell PD-L1 expression ≥ 1%. The EC’s decision is based on results from the Phase 3 CheckMate -648 trial, in which Opdivo with chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to chemotherapy alone at the pre-specified interim analysis.

For patients with esophageal squamous cell carcinoma and PD-L1 tumor proportion score ≥ 1%, nivolumab plus CT, or nivolumab plus ipilimumab is recommended.

Adults with previously untreated, unresectable advanced, recurrent, or metastatic ESCC were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W) or chemo....Responses were more durable and a larger proportion of responders had a duration of response (DOR) ≥ 24 mo with NIVO + chemo and NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% (22%, 36%, 13%, respectively) and all randomized pts (21%, 29%, 13%)….NIVO + chemo and NIVO + IPI continued to demonstrate clinically meaningful survival benefit vs chemo, durable objective responses, and acceptable safety profiles with longer follow-up.

Bristol Myers Squibb (NYSE: BMY) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Opdivo (nivolumab) in combination with fluoropyrimidine- and platinum-based chemotherapy for the first-line treatment of adult patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) with PD-L1 expression ≥ 1%...The positive opinion is based on results from the Phase 3 CheckMate -648 trial, which showed that treatment with Opdivo plus chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to chemotherapy alone at the pre-specified interim analysis in patients with unresectable advanced, recurrent, or metastatic ESCC with tumor cell PD-L1 expression ≥1% (median, 15.4 months vs 9.1 months, HR = 0.54; 99.5% CI: 0.37 to 0.80; p-value <0.001).

...overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both among patients with tumor-cell PD-L1 expression of 1% or greater (median, 15.4 vs. 9.1 months; hazard ratio, 0.54; 99.5% confidence interval [CI], 0.37 to 0.80; P<0.001) and in the overall population (median, 13.2 vs. 10.7 months; hazard ratio, 0.74; 99.1% CI, 0.58 to 0.96; P=0.002). Overall survival was also significantly longer with nivolumab plus ipilimumab than with chemotherapy among patients with tumor-cell PD-L1 expression of 1% or greater (median, 13.7 vs. 9.1 months; hazard ratio, 0.64; 98.6% CI, 0.46 to 0.90; P=0.001) and in the overall population (median, 12.7 vs. 10.7 months; hazard ratio, 0.78; 98.2% CI, 0.62 to 0.98; P=0.01).

...NIVO + chemo and NIVO + IPI led to statistically significant improvement in OS vs chemo in pts with tumor cell PD-L1 ≥ 1%...NIVO plus chemo and NIVO plus IPI both demonstrated superior OS vs chemo, along with durable objective responses and acceptable safety.

Bristol Myers Squibb...today announced positive topline results from the Phase 3 CheckMate -648 trial evaluating treatment with Opdivo (nivolumab) plus chemotherapy or Opdivo plus Yervoy (ipilimumab) in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC)....In the Opdivo plus chemotherapy arm, patients received treatment with Opdivo...fluorouracil...and cisplatin….Opdivo plus chemotherapy demonstrated a statistically significant and clinically meaningful benefit for the primary and secondary endpoints of overall survival (OS) in patients whose tumors express PD-L1...

Among all pts randomized to NIVO + chemo (n = 321), NIVO + IPI (n = 325), or chemo (n = 324), PFS2 favored NIVO + chemo (HR 0.64, 95% CI 0.54–0.77) and NIVO + IPI (HR 0.74, 95% CI 0.62–0.88) vs chemo. ORR (95% CI) was 47% (42–53), 28% (23–33), and 27% (22–32), respectively. More responders with NIVO + chemo or NIVO + IPI vs chemo had prolonged DOR (≥12 mo; 39%, 48%, and 23%, respectively). Efficacy data by tumor cell PD-L1 and PD-L1 combined positive score will be presented. NIVO + chemo and NIVO + IPI demonstrated favorable PFS2 and a higher proportion of pts with prolonged DOR vs chemo, as well as acceptable safety profiles.

A significantly longer PFS was observed in patients with a CPS ≥ 20 (7.5 [95% CI 1.8-13.1] vs. 1.9 [1.4-2.3] months, P = 0.05),…

PD‐L1 positivity of tumor cell was possibly associated with better PFS (2.04 vs 1.41 months, cut‐off 1%) and OS (11.33 vs 6.24 months, cut‐off 1%)....Nivolumab demonstrated continued long‐term efficacy, as seen by the stability of PFS and OS, in Japanese patients with esophageal squamous cell carcinoma.