New Drug Combination Maintains Quality of Life for Patients with Colorectal, Liver Cancers

Two large studies demonstrating patient-reported outcomes showed that quality of life was maintained longer with newer drug combinations compared with standard of care for the treatment of patients with a specific type of colorectal cancer (CRC) and unresectable hepatocellular carcinoma (HCC). The results were presented at the 2020 Gastrointestinal Cancers Symposium in San Francisco, California, from January 23-25.

The first study analyzed the combination of atezolizumab and bevacizumab and how it delayed declines in quality of life. The trial compared the 2-drug treatment with sorafenib, the standard of care, for patients with HCC.

Atezolizumab is a programmed cell death ligand 1 (PD-L1) inhibitor, whereas bevacizumab is a vascular endothelial growth factor inhibitor.

The results come from the phase 3 IMbrave 150 trial, which compared atezolizumab plus bevacizumab with sorafenib alone as a first-line treatment for patients with HCC who had not received prior systemic therapy.

The primary endpoint of overall survival (OS) was presented at the European Society for Medical Oncology (ESMO) Congress in November 2019. At ESMO, the investigators presented that the median OS had not yet been reached for atezolizumab plus bevacizumab compared with OS of 13.2 months for patients receiving sorafenib alone. The overall response rate was 27% with atezolizumab plus bevacizumab and 12% for sorafenib.

Researchers at the Gastrointestinal Cancers Symposium presented patient-reported outcomes from the study, including time to deterioration assessed by 2 validated patient-reported quality of life tools. The time to deterioration was defined as a decrease of 10 points from baseline in key patient-reported outcomes.

At baseline, every 3 weeks during therapy and every 3 months after discontinuation of therapy, patients completed 2 questionnaires to assess quality of life, physical functioning, and role functioning. Questionnaire completion rates were approximately 92%.

For the combination treatment, time to deterioration was a median of 11.2 months compared with 3.6 months for sorafenib. Declines in physical functioning were also delayed with the combination treatment, with a median delay of 13.1 months with atezolizumab and bevacizumab compared with 4.9 months for sorafenib.

In the second study, patient-reported outcomes improved with double- and triple-drug treatments compared with current standard of care options for patients with a particular type of colorectal cancer. Patients with CRC who have a BRAF V600E mutation treated with encorafenib and cetuximab, with or without binimetinib, were able to maintain their quality of life longer than those treated with 1 of 2 standard of care regimens. The regimens consist of irinotecan plus cetuximab or FOLFIRI (leucovorin, calcium folinate, fluorouracil, and irinotecan) with cetuximab.

The findings come from the phase 3, open-label BECON CRC trial (binimetinib, encorafenib, and cetuximab combined to treat BRAF-mutant CRC) that included 655 patients.

Previously published efficacy data in the New England Journal of Medicine found the median OS was 9.0 and 8.4 months with the triplet and doublet targeted treatments. Meanwhile, the control group of patients was 5.4 months, who received irinotecan plus cetuximab or FOLFIRI plus cetuximab.

Researchers at the Gastrointestinal Cancers Symposium reported on quality of life, which was a secondary endpoint of the study and was assessed at baseline. After every treatment cycle, 4 validated measurement tools were used, including: the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire, Functional Assessment of Cancer Therapy, EuroQol 5D 5L, and the Patient Global Impression of Change.

Specifically, the researchers looked at the time to 10% or greater deterioration between the study arms, which is considered to represent a clinically meaningful decline in quality of life. Patients treated with the triplet had a 44% to 45% reduction in the risk of quality of life deterioration, compared with patients in the standard of care group based on 2 of the measures. Patients who received the doublet had a roughly 46% reduction in risk.

The EuroQuol 5D 5L and Patient Global Impression of Change saw similar results and there was no significant difference in quality of life for patients in the triplet and doublet groups.

REFERENCE

New drug combinations maintain quality of life for patients with colorectal and liver cancers [news release]. Alexandria, VA; ASCO: January 21, 2020. https://www.asco.org/about-asco/press-center/news-releases/new-drug-combinations-maintain-quality-life-patients. Accessed January 24, 2020.