Patient-Reported Outcomes Show Newer Drug Combinations Maintain Quality of Life Longer Than Current Standard-of-Care Treatments

Multiple studies showed improved patient outcomes and increased quality of life (QOL) among various treatments that previously demonstrated clinical benefits. These patient-centric findings, along with a promising new combination therapy for patients with advanced hepatocellular carcinoma (HCC) highlight some of the latest research to come out of the 2020 Gastrointestinal Cancers Symposium, held January 23-25, in San Francisco, California.

Quality of Life Assessment in the BEACON CRC Trial

Results from the phase III BEACON CRC study demonstrated that patients with BRAF V600E-mutant metastatic colorectal cancer treated with encorafenib (Braftovi) plus cetuximab (Erbitux), with or without binimetinib (Mektovi), reported substantial improvement in QOL when compared with either of the two current standard-of-care regimens of irinotecan plus cetuximab or FOLFIRI (leucovorin, calcium folinate, fluorouracil, and irinotecan) with cetuximab.¹

Four QoL instruments were utilized in the study: European Organisation for the Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), Functional Assessment of Cancer Therapy-Colorectal (FACT-C), EuroQoL 5D-5L (EQ-5D-5L), and Patient Global Impression of Change (PGIC). Reduction in the risk of QOL deterioration was estimated at 45% (hazard ratio (HR), 0.55; 95% CI, 0.43-0.70) and 44% (HR, 0.56; 95% CI, 0.44-0.71) in the EORTC QLQ-C30 and FACT-C assessments, respectively, for the triplet therapy, compared with the control arm. Moreover, the reduction in risk of QOL deterioration was estimated at 46% (HR, 0.54; 95% CI, 0.43-0.69) and 43% (HR, 0.57; 95% CI, 0.45-0.72) in EORTC QLQ-C30 and FACT-C measures, respectively, in favor of doublet therapy. The investigators observed similar results in the EQ-5D-5L and PGIC assessments, with no overall differences in QOL shown between triplet and doublet therapy across all 4 instruments.

These findings were a secondary endpoint in the BEACON CRC trial. Results from the prespecified interim analysis were previously published in the New England Journal of Medicine,² and demonstrated an increase in median overall survival (OS) versus the control arm in both the triplet (9.0 months vs 5.4 months) and doublet (8.4 months vs 5.4 months) regimens.

At the symposium, Scott Kopetz, MD, PhD, associate professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center in Houston said:  “We recognized that safety doesn’t always capture the patient experience and that is the rational for incorporating QOL metrics into the study. This is an important component that really helps to understand the patient experience and complements the clinical efficacy endpoint.”

Patient-Reported Outcomes in the IMbrave150 Trial

Combination treatment of atezolizumab (Tecentriq) plus bevacizumab (Avastin) led to significantly better patient-reported outcomes than treatment with sorafenib (Nexavar) in patients with unresectable hepatocellular carcinoma (HCC).³

Of the 501 patients enrolled in the phase III IMbrave150 trial, at least 92% completed the EORTC QLQ-C30 and the HCC-specific EORTC QOL Questionnaire (EORTC QLQ-HCC18) during treatment. Delays in median time to deterioration (TTD) were reported in QOL (11.2 months vs 3.6 months; HR, 0.63; 95% CI, 0.46-0.85), physical functioning (13.1 months vs 4.9 months; HR, 0.53; 95% CI, 0.39-0.73), and role functioning (9.1 months vs 3.6 months; HR, 0.62; 95% CI, 0.46-0.84).⁴

Median TTD was also delayed for several disease-related symptoms, including appetite loss, fatigue, pain, and diarrhea for the atezolizumab/bevacizumab combination versus sorafenib.

The findings, along with previously published data indicating significant improvements in both OS and progression-free survival (PFS), lend support to establishing an atezolizumab/bevacizumab combination as the new standard of care.

“These [patient-reported outcomes]-the patients’ voice-further support the positive benefit-risk profile of atezolizumab and bevacizumab versus sorafenib,” said study presenter Peter R. Galle, MD, PhD, of the University Medical Center Mainz, Germany, “and in a nice way complement the efficacy data in these patients with unresectable HCC who have not received prior systemic therapy.”

Nivolumab Triplet Therapy in Advanced HCC Treatment

The triplet regimen of nivolumab (Opdivo), ipilimumab (Yervoy), and cabozantinib (Cabometyx) induced clinically meaningful responses in patients with advanced HCC who were treatment-naïve or resistant to or intolerant of sorafenib. The cohort data presented at the symposium is the first report of efficacy and safety of nivolumab and cabozantinib, with or without ipilimumab.

Seventy-one patients with advanced HCC were randomized to receive the nivolumab/ipilimumab/cabozantinib regimen (n = 35) or a doublet therapy of nivolumab combined with cabozantinib (n = 36). Investigator-assessed objective response rate (ORR) for the nivolumab/ipilimumab/cabozantinib arm was 29%, with a disease control rate (DCR) of 83%. Median PFS was 6.8 months (95% CI, 4.0-14.3), while the median OS had not yet been reached (95% CI, 15.1-not reached).⁴

For patients with advanced HCC who received the doublet therapy of nivolumab plus cabozantinib, the investigator-assessed ORR was 19% and the DCR was 75%; median PFS was 5.4 months (95% CI, 3.2-10.9) and median OS was 21.5 months (95% CI, 13.1-not reached).⁵ No new safety signals were observed in either arm.

“Patients with advanced liver cancer need new and effective treatment options,” lead investigator Thomas Yau, MD, of the Department of Medicine, University of Hong Kong, said in a statement.⁶ “Based on the cohort 6 findings, cabozantinib in combination with immunotherapy offers a potentially powerful and attractive new treatment approach that warrants further study in advanced liver cancer populations.”

Financial Disclosure:The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References:

References

1. Kopetz S, Grothey A, Van Cutsem E, et al. Encorafenib plus cetuximab with or without binimetinib for BRAF V600E-mutant metastatic colorectal cancer: quality-of-life results from a randomized, three-arm, phase III study versus the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC). Presented at: Gastrointestinal Cancers Symposium; January 23-25, 2020; San Francisco, CA. Abstract 8.

2. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med. 2019;381(17):1632-1643. doi: 10.1056/NEJMoa1908075.

3. Galle PR, Finn RS, Qin S, et al. Patient-reported outcomes (PROs) from the phase III IMbrave150 trial of atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC). Presented at: Gastrointestinal Cancers Symposium; January 23-25, 2020; San Francisco, CA. Abstract 476.

4. Mounting data support combination atezolizumab/bevacizumab as a new first-line standard of care in advanced HCC [news release]. Alexandria, VA: American Society of Clinical Oncology; January 27, 2020. https://dailynews.ascopubs.org/do/10.1200/ADN.20.200021/full/. Accessed February 3, 2020.

5. Yau T, Zagonel V, Santoro A, et al. Nivolumab (NIVO) + ipilimumab (IPI) + cabozantinib (CABO) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): results from CheckMate 040. Presented at: Gastrointestinal Cancers Symposium; January 23-25, 2020. San Francisco, CA. Abstract 478.

6. Exelixis announces results for combination of cabozantinib and nivolumab with or without ipilimumab in advanced hepatocellular carcinoma [news release]. Alameda, CA: Exelixis, Inc; January 24, 2020. https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-results-combination-cabozantinib-and. Accessed February 3, 2020.