Patient-reported outcomes from two large studies show that quality of life is maintained longer with newer drug combinations compared with standard-of-care treatments in patients with unresectable hepatocellular carcinoma and BRAF V600E–mutant metastatic colorectal cancer. The results, from analyses of the IMbrave150 and BEACON CRC trials, will be presented by Galle et al (Abstract 476) and Kopetz et al (Abstract 8), respectively, at the 2020 Gastrointestinal (GI) Cancers Symposium.
Quality of Life Maintained for Patients Treated With Atezolizumab/Bevacizumab for Unresectable Hepatocellular Carcinoma
The combination of atezolizumab and bevacizumab delayed declines in quality of life in the phase III IMbrave 150 trial, which compared the two-drug treatment with sorafenib (the standard of care) for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy. Atezolizumab is a programmed cell death ligand 1 inhibitor, and bevacizumab is a vascular endothelial growth factor inhibitor.
“Because it reflects both the effects of disease and the side effects of treatment, sustained or improved quality of life is particularly important for patients,” said lead author Peter R. Galle, MD, PhD, of the University Medical Center in Mainz, Germany. “Patients with liver cancer are typically more fragile and frail than [patients with other cancers]. Toxicity of the treatments can be much more serious for these patients, and their quality of life can decline quite quickly.”
The primary endpoint of the trial—overall survival—was reached, and data was presented at the European Society for Medical Oncology Asia Congress in November 2019. At that time, median overall survival had not yet been reached for atezolizumab/bevacizumab compared with overall survival of 13.2 months for patients receiving sorafenib alone. The overall response rate was 27% with atezolizumab plus bevacizumab and 12% for sorafenib.
At the Gastrointestinal Cancers Symposium, researchers will present patient-reported outcomes results from the study. Time to deterioration, assessed by two validated patient-reported quality of life tools, was a prespecified secondary endpoint of the study. 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 two questionnaires to assess quality of life, physical functioning, and role functioning. Questionnaire completion rates were about 92%.
“High-quality patient-reported outcomes results from IMbrave150 showed large and consistent benefits in key aspects of the patient experience with atezolizumab/bevacizumab, further supporting its overall clinical benefit in patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.”— Galle et al
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Median time to deterioration was 11.2 months for the combination treatment 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/bevacizumab compared with 4.9 months for sorafenib. Atezolizumab/bevacizumab also delayed time to deterioration in patient-reported appetite loss, fatigue, pain, and diarrhea vs sorafenib; a lower proportion of patients treated with atezolizumab/bevacizumab experienced clinically meaningful deterioration in each of these symptoms vs patients treated with sorafenib.
The researchers concluded, “High-quality patient-reported outcomes results from IMbrave150 showed large and consistent benefits in key aspects of the patient experience with atezolizumab/bevacizumab, further supporting its overall clinical benefit in patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.”
Quality of Life With Double- and Triple-Drug Regimens in BRAF V600E–Mutant Metastatic Colorectal Cancer
Patient-reported outcomes improved with double- and triple-drug treatments compared with current standard of care options for patients with BRAF V600E–mutated metastatic colorectal cancer. When these patients were treated with encorafenib and cetuximab with or without binimetinib, they were able to maintain their quality of life longer than those treated with one of two standard-of-care regimens, consisting of irinotecan plus cetuximab or FOLFIRI (leucovorin, calcium folinate, fluorouracil, and irinotecan) with cetuximab. The BRAF V600E mutation occurs in about 10% of patients with colorectal cancer, and can confer a poor prognosis.
Scott Kopetz, MD, PhD, FACP
“The findings highlight that with these novel targeted therapy regimens, not only was disease controlled longer, but patient-reported quality of life was maintained longer,” said lead author Scott Kopetz, MD, PhD, FACP, Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center.
The findings come from the open-label, phase III BEACON CRC trial, which included 655 patients. Binimetinib and encorafenib are inhibitors of proteins involved in cancer cell growth.
Efficacy data from the trial was published in October 2019 in The New England Journal of Medicine. The median overall survival was 9.0 and 8.4 months with the triplet and doublet targeted treatments, respectively, compared to 5.4 months in the control group of patients, who received irinotecan plus cetuximab or FOLFIRI plus cetuximab.
At the Gastrointestinal Cancers Symposium, researchers will report on quality of life, which was a secondary endpoint of the study. Quality of life was assessed at baseline and after every treatment cycle using four validated measurement tools: the European Organisation for Research and Treatment of Cancer QOL Questionnaire, Functional Assessment of Cancer Therapy, EuroQol 5D 5L, and the Patient Global Impression of Change. In particular, the researchers looked at the time to ≥ 10% deterioration between the study arms, which is considered to represent a clinically meaningful decline in quality of life.
“In BEACON CRC, triplet and doublet [regimens] demonstrated substantial improvement in patient-reported quality of life assessments over the current standard of care in patients with BRAF V600E–mutant metastatic colorectal cancer whose disease had progressed after one or two prior regimens.— Kopetz et al
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Patients treated with the triplet had a roughly 44% to 45% reduction in the risk of quality-of-life deterioration compared with patients in the standard-of-care group, based on two of the measures. Those receiving the doublet had a roughly 46% reduction in risk. Similar results were seen with the EuroQuol 5D 5L and Patient Global Impression of Change. There was no significant difference in quality of life for patients in the triplet and doublet groups.
The researchers concluded, “In BEACON CRC, triplet and doublet [regimens] demonstrated substantial improvement in patient-reported quality-of-life assessments over the current standard of care in patients with BRAF V600E–mutant metastatic colorectal cancer whose disease had progressed after one or two prior regimens.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org (Abstract 476 and Abstract 8).
