For perspective on CheckMate 8HW, The ASCO Post interviewed Alan P. Venook, MD, FASCO, the Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California San Francisco and the Shorenstein Associate Director for Program Development at the Helen Diller Family Comprehensive Cancer Center. Although Dr. Venook was impressed with the findings, he remains concerned about some of the unsettled issues and hopes further analysis of this study will provide answers.
Alan P. Venook, MD, FASCO
“This study may very well be another move forward in the treatment of patients with metastatic colorectal cancer. The results are very compelling—they could be hugely important—but we don’t have overall survival data, so it’s an incomplete data set,” Dr. Venook said. “I’m worried the progression-free survival data may be accurate at the point of inflection, but it’s important also to capture the second disease progression. We need to see the full data, and we need to see the comparison between nivolumab/ipilimumab and nivolumab alone.”
“Furthermore, I think the most important cohort were not the patients who benefited from the therapy, but the 25% to 30% who appeared to get no benefit whatsoever from immunotherapy,” Dr. Venook explained. “Why is that? Why did every patient with stage 2 or 3 rectal cancer respond to dostarlimab-gxly,1 but here one-third did not respond to immunotherapy? This is an opportunity to understand resistance to checkpoint inhibitors, so I’m hoping there are plans to analyze that subset. That may very well hold the key to understand how we can get other patients to benefit from the same category of drugs.”
DISCLOSURE: Dr. Venook reported financial relationships with Merck Sharp & Dohme, Amgen, GlaxoSmithKline, Exelixis, BridgeBio Pharma, Bayer Health, Gilead Sciences, Exact Sciences, Bristol Myers Squibb Foundation/Janssen, Pfizer, and Up-to-Date.
REFERENCE
1. Cercek A, Lumish M, Sinopoli J, et al: PD-1 blockade in mismatch repair–deficient, locally advanced rectal cancer. N Engl J Med 386:2363-2376, 2022.
