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Meta Description: New guidance and expert discussion clarify the role of PD-L1 CPS scores in determining immunotherapy use for advanced esophageal and gastric cancers.
The treatment landscape for advanced esophageal and gastric cancers is becoming increasingly nuanced, especially regarding the integration of immune checkpoint inhibitors. Current NCCN guidelines recommend adding these agents for patients with a PD-L1 combined positive score (CPS) of at least 1, tho a Category 1 preference is reserved for those with a CPS of 5 or greater. Recent discussions at a virtual Case-Based Roundtable event, led by yelena Y. Janjigian, MD, chief of the gastrointestinal oncology service at Memorial Sloan Kettering Cancer Center, highlighted the complexities of interpreting PD-L1 scores and maximizing the benefit.
Despite this, many clinicians are adopting a more liberal approach, particularly given the potential for limited subsequent treatment options.
Several physicians at the roundtable reported utilizing a CPS threshold of 1 for initiating discussions about IO with patients. One oncologist stated, “I use a CPS of 1 to discuss IO with the patient. If Claudin18.2 is negative, I have a discussion with the patient about the potential benefit and the adverse events and have shared decision-making, as if you don’t offer IO in the first line, this is the only chance to use this drug, and they will probably be one of the patients that will respond.”
Addressing Discordance and Variability in PD-L1 Testing
A notable concern raised during the discussion was the inconsistency of PD-L1 testing across different institutions. Janjigian shared her experience with frequent discordance between PD-L1 results from different labs, sometimes even from repeat testing of the same sample.
“What I’ve seen in practice is the discordance between several different testings of the same sample,” she noted. “PD-L1 testing is not that reliable. I often retest.” This variability stems from differences in sample quality, testing methodologies (tumor proportion score vs. CPS), and pathologist interpretation.
To mitigate this, many centers, like those represented at the roundtable, now perform PD-L1, HER2, and mismatch repair (MMR) testing in-house and upfront, ensuring results are available when the patient is first seen.
Clinical Scenarios and Second-Line Options
The discussion also explored specific clinical scenarios. One case involved a patient who had progressed on FOLFOX chemotherapy and trastuzumab for HER2-positive disease, without prior PD-L1 testing. Experts agreed that adding an anti-PD-1 agent was warranted,even though the patient was beyond the initial first-line setting,provided that they remained fit for therapy. The rationale was to maximize the potential for benefit before considering second-line options like trastuzumab deruxtecan (T-DXd).
For patients who fail chemotherapy and IO, treatment options become more limited. A taxane combined with ramucirumab was suggested for gastric cancer, while carboplatin/paclitaxel or paclitaxel were recommended for squamous histology. However, it was noted that ramucirumab is not approved for squamous cancers. for HER2-positive disease, T-dxd remains a key consideration, although one physician cautioned that some patients may experience performance status decline with this agent.
The Importance of Early, Effective therapy
Given the limited number of patients who receive more then one line of therapy, the consensus was that utilizing the most effective treatment upfront is crucial. The roundtable emphasized the need for a proactive approach to biomarker testing and a willingness to consider IO even in cases with lower CPS scores, acknowledging the potential for individual patient responses and the challenges of accurately assessing PD-L1 expression.
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The NCCN guidelines, coupled with expert insights, are continually refining the approach to immunotherapy in advanced esophageal and gastric cancers, aiming to optimize outcomes for patients facing these challenging diagnoses.
