Frontline Pembrolizumab Improves Health-Related QOL in DNA Repair-Deficient Metastatic CRC

Frontline pembrolizumab (Keytruda) induced clinically meaningful improvements in the health-related quality of life (HRQoL) of patients with microsatellite instability-high (MSI-H) and/or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) compared with standard-of-care (SOC) chemotherapy, according to new research presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“These findings further support use of pembrolizumab as a standard of care for first-line treatment of patients with MSI-H/dMMR mCRC,” Thierry André, MD, the study’s lead author, said in an oral presentation at the virtual conference.

The Phase III KEYNOTE-177 study analyzed 294 treatment-naïve U.S. patients with MSI-H and/or dMMR mCRC. In that study, researchers demonstrated that, in comparison to chemotherapy (mFOLFOX6 or FOLFIRI) with or without bevacizumab or cetuximab, pembrolizumab alone provided superior progression-free survival (PFS). In the current analysis, the investigators found that immunotherapy sparked an increase in HRQoL over 2 years compared with chemotherapy.

Patients were randomized 1:1 to take either pembrolizumab (n=152) or SOC chemotherapy (n=142) with or without bevacizumab or cetuximab. In a follow-up at 18 weeks, clinically meaningful improvement was found based on the results of 2 validated, self-reported questionnaires, measuring against a baseline score of 0. The QLQ-C30 global health status quality-of-life scale found a least-squares mean (LSM) score change of 8.96 (95% CI, 4.24-13.69; P = .0002) and the EQ-5D VAS demonstrated an LSM increase of 7.38 (95% CI, 2.82-11.93; P = .0016) for patients receiving pembrolizumab compared with chemotherapy. According to data presented at the ESMO virtual congress, during the time period 18-45 weeks after the start of treatment, the LSM score for patients receiving pembrolizumab improved by another 5-10 points, while the score for those taking chemotherapy dropped by several points.

Another questionnaire, QLQ-CR29, showed that patients taking pembrolizumab reported improvements in anxiety, weight and, for men, sexual interest between baseline and week 18; patients taking chemotherapy also saw an improvement in anxiety but reported declines in body image and, among men, sexual interest. Sexual interest dropped for women on both regimens.

Moreover, time to deterioration, including physical and social functioning and fatigue, was delayed in patients who received pembrolizumab versus chemotherapy (HR, 0.50; 95% CI, 0.32-0.81; P=0.0016). For instance, in looking at the probability of no physical deterioration during

that period, researchers noted 29 documented events in patients taking pembrolizumab compared with 45 events for patients taking chemotherapy.

Adverse effects such as urinary frequency, abdominal pain, bloating and stoma care problems improved over time with pembrolizumab, while issues including buttock pain, dry mouth, alopecia, taste alterations and sore skin increased with chemotherapy.

These data provide further proof that pembrolizumab monotherapy is a viable treatment for patients with MSI-H and/or dMMR mCRC in the first-line setting, said Andre, head of the Medical Oncology Department at the Saint Antoine Hospital, Assistance Publique Hôpitaux de Paris, emphasized that meaningful improvements in quality of life were seen with pembrolizumab but not with chemotherapy, adding that further study is warranted. André did caution that results were limited to the treatment period, and while this immunotherapy works well, especially in the PD-L1 pathway, its usefulness can be limited depending on whether a patient’s disease is resistant to treatment.

Reference:

Andre T, Amonkar M, Norquist J, et al. Health-related quality of life (HRQoL) in patients (pts) treated with pembrolizumab (pembro) vs chemotherapy as first-line treatment in microsatellite instability-high (MSI-H) and/or deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC): Phase III KEYNOTE-177 study. Presented at: European Society of Medical Oncology Virtual Congress 2020; September 19- 21, 2020; Virtual. Abstract 396O.