On February 10,2022,the U.S.Food and Drug Administration(FDA)’s Oncologic Drugs Advisory Committee voted 14-1 against using data from the ORIENT-11 trial to support a biologics license application for sintilimab inje...On February 10,2022,the U.S.Food and Drug Administration(FDA)’s Oncologic Drugs Advisory Committee voted 14-1 against using data from the ORIENT-11 trial to support a biologics license application for sintilimab injection plus pemetrexed and platinum-based chemotherapy as first-line treatment for patients with nonsquamous non-small cell lung cancer(NSCLC)1.One major reason was that the FDA claimed overall survival(OS)was not statistically tested in ORIENT-11,while previous regular approvals were granted on the basis of statistically significant improvements in OS2.This may be a surprise to some physicians,as the ORIENT-11 trial previously reported improved OS with a hazard ratio(HR)of 0.60(95%confidence interval[CI]:0.45–0.79)and a P value of 0.00033,which is far below the commonly accepted threshold of 0.05 for declaring statistical significance.Some may argue that the OS results of ORIENT-11 were not considered statistically significant by the FDA because OS was only a secondary endpoint.However,in the KEYNOTE-024 trial4,which compared pembrolizumab with chemotherapy in patients with previously untreated advanced NSCLC with PD-L1 expression on at least 50%of tumor cells,OS was also a secondary endpoint.Nevertheless,the OS benefit of the KEYNOTE-024 trial was acknowledged by the FDA and included in the drug label5.The fundamental reason why OS results of ORIENT-11 were not considered statistically significant by the FDA is that the OS endpoint was not included in the multiplicity control strategy.展开更多
文摘On February 10,2022,the U.S.Food and Drug Administration(FDA)’s Oncologic Drugs Advisory Committee voted 14-1 against using data from the ORIENT-11 trial to support a biologics license application for sintilimab injection plus pemetrexed and platinum-based chemotherapy as first-line treatment for patients with nonsquamous non-small cell lung cancer(NSCLC)1.One major reason was that the FDA claimed overall survival(OS)was not statistically tested in ORIENT-11,while previous regular approvals were granted on the basis of statistically significant improvements in OS2.This may be a surprise to some physicians,as the ORIENT-11 trial previously reported improved OS with a hazard ratio(HR)of 0.60(95%confidence interval[CI]:0.45–0.79)and a P value of 0.00033,which is far below the commonly accepted threshold of 0.05 for declaring statistical significance.Some may argue that the OS results of ORIENT-11 were not considered statistically significant by the FDA because OS was only a secondary endpoint.However,in the KEYNOTE-024 trial4,which compared pembrolizumab with chemotherapy in patients with previously untreated advanced NSCLC with PD-L1 expression on at least 50%of tumor cells,OS was also a secondary endpoint.Nevertheless,the OS benefit of the KEYNOTE-024 trial was acknowledged by the FDA and included in the drug label5.The fundamental reason why OS results of ORIENT-11 were not considered statistically significant by the FDA is that the OS endpoint was not included in the multiplicity control strategy.
