The FDA’s Oncologic Drugs Advisory Committee will meet on Thursday, September 26th to discuss the use of immune checkpoint inhibitors (ICIs) in patients battling unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma, along with esophageal squamous cell carcinoma. Currently, the FDA’s approval for these ICIs in these cancers is broad, applying to all patients regardless of their programmed death cell ligand-1 (PD-L1) expression levels. However, the FDA is now taking a closer look at the effectiveness and safety of these drugs based on PD-L1 expression, a key biomarker that helps predict how well a treatment will work.
Emerging data suggests that PD-L1 expression plays a significant role in determining the efficacy of ICI treatment in these cancers. However, different clinical trials have used varied methods to assess PD-L1 expression and differing thresholds to define a positive result. The review will encompass approved ICIs like Bristol Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab), Merck & Co Inc.’s Keytruda (pembrolizumab), and pending applications for BeiGene Inc.’s Tevimbra (tislelizumab).
The FDA’s briefing document indicates that combining ICIs with standard chemotherapy might not offer any benefit for patients with low PD-L1 expression (below 1%). Patients with PD-L1 levels of 10% or higher appear to experience the most significant benefits. The effectiveness for patients with PD-L1 levels between 1% and 10% remains unclear, making data interpretation challenging.
The FDA emphasizes that patients with low or absent PD-L1 expression are unlikely to benefit from ICI therapy. In fact, administering anti-PD-1 therapy in these patients could pose risks, including severe immune-related adverse effects that can further diminish their quality of life. The FDA states, “Although these results are exploratory… strong evidence does not appear to support the use of anti-PD-L1 drugs in patients with low PD-L1 expression.”
This review by the FDA is expected to have a significant impact on the use of ICIs in treating gastric and esophageal cancers, potentially leading to more targeted and personalized approaches for patient treatment. It underscores the importance of considering PD-L1 expression as a key factor in determining the best treatment strategy for these challenging cancers.
