Tanja Obradovic: FDA ODAC’s decision on PD-1 Inhibitors in HER2- Negative Gastric Cancer

Tanja Obradovic shared a post on LinkedIn:

“In highly anticipated discussion on September 26th FDA Oncologic Drugs Advisory Committee (ODAC) voted 10 to 2 (1 abstention) against the positive risk-benefit profile of PD-1 inhibitors in the first-line treatment of patients with advanced HER2-negative, microsatellite stable (MSS) gastric/gastroesophageal junction (GEJ) adenocarcinoma with a PD-L1 expression of less than 1.(LINK)

Evaluation of data from the Check Mate 649 (NCT02872116 by BRYSTOL MYERS SQUIBB SL), KEYNOTE-859 (NCT03675737 by Merck), and RATIONALE-305 (NCT03777657 by BeiGene) was quite extensive. Of interest to note is that 3 studies used different methodology for PDL-1 expression levels (combined positive score (CPS with different Abs for CheckMate and Keynote studies) and tumor area positivity score (TAP for Rationale study) but efficacy results for patients deemed PDL-1 negative (less than 1 CPS or TPS) were of similar magnitude.

Discussion of the panel led to overwhelming vote toward conclusion that in this patient population totality of the data does not support continued current indication for PD-1 inhibitors since hazard ratios for overall survival (OS) are close to 1 while treatments resulted in substantial toxicities. With minimal benefit in OS toxicity matters-addition of a PD-1 inhibitor to chemotherapy adds anywhere from 3% to 11% increase in the proportion of patients experiencing grade 3/4 treatment-related adverse effects.
It will be of interest to see if this kind of evaluation of benefit magnitude vs toxicity in the context of PDL-1 expression proceeds to other indications currently approved for PD(L)1 class with similar situation.”

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Source: Tanja Obradovic/LinkedIn

Tanja Obradovic is the Vice President of Oncology Scientific Affairs at ICON PLCh. She has over 20 years of clinical research experience and has led major pharmaceutical companies for 13 years. Her research focuses on small molecules, antibodies, cell and gene therapy, and major immunotherapy of PD1 inhibitors.