FDA approves two Opdivo- based regimens as first-line treatments for unresectable, advanced or metastatic esophageal squamous cell carcinoma- BMS

The approvals are based on the Phase III CheckMate -648 trial, which evaluated Opdivo in combination with chemotherapy (n=321) and Opdivo plus Yervoy (n=325) each compared to chemotherapy alone (n=324), and was the largest Phase III trial of an immunotherapy in first-line ESCC.

In the trial, Opdivo in combination with chemotherapy demonstrated superior overall survival (OS) compared to chemotherapy alone, both in all randomized patients, a secondary endpoint, which was hierarchically tested (Hazard Ratio [HR] 0.74, 95% Confidence Interval [CI]: 0.61 to 0.90, P=0.0021) and in patients whose tumors express PD-L1 ( greater than 1%), a primary endpoint (HR 0.54, 95% CI: 0.41 to 0.71, P<0.0001). in all randomized patients the median os (mos) was 13.2 months (95% ci: 11.1 to 15.7) with opdivo in combination with chemotherapy versus 10.7 months (95% ci: 9.4 to 11.9) with chemotherapy alone. in patients whose tumors express pd-l1 ( greater than 1%) the mos was 15.4 months (95% ci: 11.9 to 19.5) for opdivo in combination with chemotherapy versus 9.1 months (95% ci: 7.7 to 10) with chemotherapy alone. the median progression-free survival (pfs) in all randomized patients, which was a hierarchically tested secondary endpoint, was 5.8 months (95% ci: 5.6 to 7.0) for opdivo in combination with chemotherapy and 5.6 months (95% ci: 4.3 to 5.9) for chemotherapy alone (hr="0.81;" 95% ci: 0.67 to 0.99, p="not" significant). per pre-specified analysis, pfs did not meet statistical significance. the median pfs in patients whose tumors express pd-l1 ( greater than 1%), which was a co-primary endpoint, was 6.9 months (95% ci: 5.7 to 8.3) for opdivo in combination with chemotherapy and 4.4 months (95% ci: 2.9 to 5.8) for chemotherapy alone (hr 0.65; 95% ci: 0.49 to 0.86, p="0.0023)."></0.0001).>

Opdivo plus Yervoy also improved OS compared to chemotherapy in all-randomized patients, a secondary endpoint, which was hierarchically tested (HR 0.78, 95% CI: 0.65 to 0.95, P=0.0110) and patients whose tumors express PD-L1 ( greater than 1%), a primary endpoint (HR 0.64, 95% CI: 0.49 to 0.84, P=0.0010). The mOS was 12.8 months (95% CI: 11.3 to 15.5) with Opdivo plus Yervoy versus 10.7 months (95% CI: 9.4 to 11.9) with chemotherapy alone in all randomized patients and 13.7 months (95% CI: 11.2 to 17.0) with Opdivo plus Yervoy versus 9.1 months (95% CI: 7.7 to 10) with chemotherapy alone in patients whose tumors express PD-L1 ( greater than 1%).

The median PFS in patients whose tumors express PD-L1 ( greater than 1%), which was a co-primary endpoint, was 4.0 months (95% CI: 2.4 to 4.9) for Opdivo plus Yervoy and 4.4 months (95% CI: 2.9 to 5.8) for chemotherapy alone (HR 1.02; 95% CI: 0.78 to 1.34, P=not significant). Per pre-specified analysis, PFS did not meet statistical significance. Median PFS in the PD-L1 ( greater than 1%) population was not statistically significant and therefore it was not hierarchically tested in the all comers population.

Opdivo alone and Opdivo plus Yervoy are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.