Salah-Eddin Al-Batran, MD

Salah-Eddin Al-Batran, MD, Director of the Institute of Clinical Cancer Research and Director of GI Oncology at Krankenhaus Nordwest-University Cancer Center, Frankfurt, Germany, commented on KEYNOTE-590 at a press briefing. Dr. Al-Batran noted that the prognosis for advanced esophageal cancer is poor, with median survival of less than 12 months in most studies. KEYNOTE-590, showing a survival benefit with pembrolizumab and chemotherapy, is “practice changing,” he commented.

Information on Lower PD-L1 Expressors Needed

Although KEYNOTE-590 is positive, Dr. Al-Batran remained curious as to the actual effect of pembrolizumab in patients with low or no PD-L1 expression; this group accounted for about 50% of the overall population. “We still don’t have enough information on the lower PD-L1 expressers, and we need longer follow-up to see the tail of the curve. The differences seen in the high expressers, however, are clinically relevant,” he said.

He would also like to see data in relation to microsatellite-high status and tumor mutational burden—factors that appear to have relevance for response to checkpoint inhibition, he added.

Dr. Al-Batran also questioned the wisdom of recommending the addition of pembrolizumab as standard of care for all patients. “I am treating an individual patient. For me, it is important to know what the efficacy is in a patient with a Combined Positive Score (CPS) of 1 to 9 or [even] 0,” he explained. To derive this information, he would conduct an analysis that excludes patients with a PD-L1 CPS ≥ 10, to ensure the positive results in the high-expressors are not inflating the overall benefit observed. “These questions have to be addressed to give us a clear picture of how to treat the patient sitting in front of us.”

He agreed with the investigators that the first-line treatment of advanced esophageal cancer should now include a checkpoint inhibitor, but that, at this time, he would likely restrict immunotherapy to patients who showed the most benefit in the trial—those with a PD-L1 CPS ≥ 10. “For the other groups, I think we should wait for more data,” he said. 

DISCLOSURE: KEYNOTE-590 was sponsored by Merck Sharp & Dohme Corp. Dr. Al-Batran holds ownership interests in Institut für Klinische Krebsforschung IKF GmbH; has served as a consultant or advisor to Bristol Myers Squibb, Celgene, Lilly, Merck, Merck Sharp & Dohme, Nordic Bioscience, and Roche; has participated in a speakers bureau for AIO GmbH, Celgene, Forum für Medizinische Fortbildung, Lilly, MCI Group, and Nordic Bioscience; and has received research funding from Celgene, the Federal Ministry of Education and Research of Germany, German Cancer Aid, German Research Foundation, Hospira, Lilly, Medac, Merck, Roche, Sanofi, and Vifor Pharma.