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Expert Point of View: Chiara Cremolini, MD, PhD


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The KEYNOTE-177 invited discussant, Chiara Cremolini, MD, PhD, of the University of Pisa, Italy, welcomed the patient-reported outcomes of the study, noting that such data are frequently missing. “Unfortunately, quality of life is an often-disregarded issue in colorectal cancer clinical trials,” she said.

Chiara Cremolini, MD, PhD

Chiara Cremolini, MD, PhD

A systematic review of 67 phase III randomized controlled trials conducted between 2012 and 2018 and published in 11 major journals found that 41 studies did not even list quality of life as an endpoint.1 In 16 of those studies, quality of life was an endpoint and was reported in a primary publication; in 5, it was listed and reported in a secondary publication; and in 5, it was listed, but the data were not reported, she said.

“Quality of life is a multidimensional and complex concept. It’s not only related to toxicity, since an increase in adverse events does not necessarily translate into a worsening quality of life. It’s a little about efficacy, but an improvement in the study’s primary outcomes does not necessarily translate into an improved quality of life,” she said. Instead, quality of life is more of a “subjective perception by the patient” that provides more useful information than either toxicity or efficacy, the goal being to capture the treatment value of a new therapeutic, she maintained.

“In KEYNOTE-177, we now have the results in terms of quality of life, and we see significant differences in score variations at week 18 vs baseline, favoring pembrolizumab. In the chemotherapy arm, we have a decline in scores. On the other side, we see improvements with the checkpoint inhibitor,” Dr. Cremolini said. She found this to be particularly interesting in light of the fact that, at week 18, the shape of the progression-free survival curves seemed to favor chemotherapy. The curves diverged later, she added.

A decline in quality of life with chemotherapy was also recently observed with a panitumumab-based regimen in the Valentino study,2 whereas improved quality of life with immunotherapy was observed in CheckMate 142 with nivolumab plus ipilimumab vs chemotherapy.3

“I agree with the KEYNOTE-177 authors,” she concluded. “Pembrolizumab is the best upfront option for patients with [microsatellite instability–high/mismatch repair–deficient] metastatic colorectal cancer.” 

DISCLOSURE: Dr. Cremolini has received honoraria from Amgen, Bayer, Roche, and Servier; has served as a consultant or advisor to Amgen, Bayer, and Roche; has participated in a speakers bureau for Servier; has received research funding from Merck; and has been reimbursed for travel, accommodations, or other expenses by Roche and Servier.

REFERENCES

1. Lombardi P, Marandino L, De Luca E, et al: Quality of life assessment and reporting in colorectal cancer: A systematic review of phase III trials published between 2012 and 2018. Crit Rev Oncol Hematol 146:102877, 2020.

2. Raimondi A, Di Maio M, Morano F, et al: Health-related quality of life in patients with RAS wild-type metastatic colorectal cancer treated with panitumumab-based first-line treatment strategy: A prespecified secondary analysis of the Valentino study. Eur J Cancer 135:230-239, 2020.

3. Overman MJ, Lonardi S, Wong KYM, et al: Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol 36:773-779, 2018.


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