Bristol Myers Squibb Announced That The Us Food And Drug Administration (Fda) Has Approved Both Opdivo (Nivolumab) (Injection For Intravenous Use) In Combination With Fluoropyrimidine- And Platinum-Containing Chemotherapy And Opdivo Plus Yervoy (Ipilimumab) As A First-Line Treatment For Adult Patients With Unresectable Advanced Or Metastatic Esophageal Squamous Cell Carcinoma (Escc) Regardless Of Pd-L1 Status.The Approvals Are Based On The Phase 3 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 3 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 Tumours Express Pd-L1 (=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.1 In Patients Whose Tumours Express Pd-L1 (=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.1 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 Tumours Express Pd-L1 (=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).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 Tumours Express Pd-L1 (=1%), A Primary Endpoint (Hr 0.64, 95% Ci: 0.49 To 0.84, P=0.0010).1,2 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 Tumours Express Pd-L1 (=1%). The Median Pfs In Patients Whose Tumours Express Pd-L1 (=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 (=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.
