The ASCO Post asked Michael Cecchini, MD, Assistant Professor of Medicine and Co-Director of the Colorectal Program in the Center for Gastrointestinal Cancer at Yale School of Medicine and Smilow Cancer Hospital Center, New Haven, to comment on the RATIONALE-306 findings.

Michael Cecchini, MD

He said the study addresses the following question: For the patient with untreated metastatic squamous cell carcinoma of the esophagus, can immune checkpoint inhibitors be added to different chemotherapy backbones to improve survival compared with the standard of care? According to Dr. Cecchini, the results of this study suggest they can.

“Findings described in RATIONALE-306 add to the existing data supporting chemoimmunotherapy as initial treatment for patients with metastatic squamous cell carcinoma of the esophagus. The study is positive in favor of tislelizumab in combination with chemotherapy as initial treatment for untreated metastatic or locally advanced esophageal squamous cell carcinoma, compared with standard-of-care chemotherapy without an immune checkpoint inhibitor. There is a clear overall survival benefit for all randomly assigned patients that is maintained in all subgroups, including those with PD-L1 expression < 10%. Additional information on lower levels of PD-L1 expression may be helpful to determine whether more nuance can be added to the interpretation of these biomarker data.”

Dr. Cecchini added that the study further supports the use of immune checkpoint inhibitors with different chemotherapy combinations (platinum plus fluoropyrimidine or platinum plus paclitaxel). “This differentiates this study from prior chemoimmunotherapy data for esophageal squamous cell carcinoma,” he pointed out.

“Given the improvement in overall survival in all subgroups and the acceptable safety profile, I agree with the authors’ conclusions that this treatment combination is likely to join the currently available options of chemotherapy plus a checkpoint inhibitor as a standard of care for first-line esophageal squamous cell carcinoma,” Dr. Cecchini concluded. 

DISCLOSURE: Dr. Cecchini owns stock or has other ownership interests in Parthenon Therapeutics; has received honoraria from Agios, Aptitude Health, AstraZeneca, DAVA Oncology, Eisai, and Macrogenics; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca and Eisai.