ABSTRACT
BACKGROUND: The BRAF inhibitor encorafenib in combination with cetuximab was recently approved for patients with BRAFV600E-mutated (BRAFV600Emut) metastatic colorectal cancer (mCRC). Approval was based on positive results from the phase 3 BEACON CRC study in BRAFV600Emut mCRC patients who had progressed after 1-2 previous regimens. This analysis provides a detailed examination of the adverse events (AEs) of interest (AEIs) with encorafenib+cetuximab in the BEACON study to aid gastrointestinal oncologists, given the limited experience with this combination. MATERIALS AND METHODS: AEIs, including dermatological AEs, arthralgia/myalgia, nausea/vomiting, diarrhea, abdominal pain, fatigue/asthenia and nephrotoxicity, were examined in the doublet therapy group. Clinical characteristics associated with these AEs, AE grade, time to onset and time to resolution were also studied. RESULTS: Safety analysis included 216/220 patients randomized to doublet therapy. The most commonly occurring AEI was dermatological toxicity (75.5%), followed by arthralgia/myalgia (56.0%) and fatigue/asthenia (56.0%). Other than nephrotoxicity (7 patients; 5/7 with Grade 3 or 4), most AEs were Grade 1 or 2. Most AEs were more common in women than men (nausea/vomiting, diarrhea, abdominal pain, dermatological AEs, and arthralgia/myalgia). Nausea/vomiting, abdominal pain and fatigue/asthenia were more common in patients aged ≥70 years. Most AEs developed early, within the first 1-2 months of treatment, and resolved within 1-2 weeks. In addition, survival outcomes were better in patients experiencing arthralgia/myalgia or dermatological toxicities. CONCLUSION: This analysis indicated that, except for rare cases of nephrotoxicity, encorafenib+cetuximab is well tolerated in most patients, with most AEIs being mild-to-moderate in severity, occurring early and resolving rapidly. CLINICAL TRIAL REGISTRATION: the BEACON study (ClinicalTrials.gov, NCT02928224; EudraCT, 2015-005805-35).
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Male , Humans , Female , Cetuximab , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Asthenia/chemically induced , Proto-Oncogene Proteins B-raf/genetics , Myalgia/chemically induced , Myalgia/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Vomiting/chemically induced , Nausea/chemically induced , Fatigue/etiology , MutationABSTRACT
For patients with metastatic colorectal cancer (mCRC) that have failed a first-line oxaliplatin-based regimen, the preferred treatment option is an irinotecan-based regimen. This prospective, observational, noncomparative, post-authorization safety study (OZONE) evaluated the safety and effectiveness of aflibercept plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) in patients with mCRC treated in daily practice after failure of an oxaliplatin-based regimen. Patients were grouped by age, renal impairment, hepatic impairment, race, number, and type of prior anticancer therapy. Of 766 treated patients enrolled, 59.5% were male, 94.8% had an Eastern Cooperative Oncology Group performance status of 0-1, all received previous chemotherapy (97.8% including oxaliplatin), and 58.6% had prior exposure to bevacizumab. At least one grade ≥ 3 treatment-emergent adverse event (TEAE) was reported in 68.3% of patients. Neutropenia, hypertension, diarrhea, and asthenia were the most frequently occurring grade ≥ 3 TEAEs. Antivascular endothelial growth factor class events were infrequent. Subgroup analyses did not reveal major differences in the safety profile according to age, renal and hepatic status, race, or prior anticancer therapy. For the total population, median overall survival was 12.5 months, median progression-free survival was 6.1 months, and overall response rate was 16.3%. Aflibercept in combination with FOLFIRI is a safe and efficacious regimen administered in current clinical practice to patients with mCRC previously treated with oxaliplatin. The study results, conducted in real-world clinical practice with a less selected patient population, are aligned with the VELOUR (NCT00561470) trial and no new safety issues were identified.
