Lumakras plus Vectibix showed improved overall survival and response rates in KRAS G12C metastatic colorectal cancer, though not statistically significant.
Lumakras (sotorasib) plus Vectibix (panitumumab) generated overall survival data and response rates, as well as earlier progression-free survival and safety findings, which support its use for patients with KRAS G12C-mutated metastatic colorectal cancer no longer responding to chemotherapy, according to study findings published in Journal of Clinical Oncology.
Notably, although these findings showed an improvement with this combination compared with investigator’s choice, it was not statistically significant.
After a median follow-up of 13.6 months, there were 24 deaths in the high-dose Lumakras/Vectibix group, 28 in the low-dose group and 30 in the investigator’s choice arm. Updated overall response rates were 30.2% with high-dose Lumakras/Vectibix, 7.5% with low-dose, and 1.9% with investigator’s choice. Compared with investigator's choice, overall survival improved with Lumakras plus Vectibix, with a 30% reduction in risk of death at 960 mg and 17% at 240 milligrams (mg).
“These findings support that the benefit provided by [Lumakras] 960 mg-[Vectibix] in progression-free survival and RECIST responses translated toward potential improvement in overall survival, even with [less than] 30% of patients in the control arm receiving KRASG12C inhibitor combination as post-trial therapy,” lead study author Dr. Filippo Pietrantonio and his collogues wrote. “As the study was not powered for overall survival, the observed hazard ratio of 0.7 and the median not being reached after 13.6 months of follow-up versus a median of 10.3 months in the control arm indicate that even if not statistically different, overall survival improvement could be particularly meaningful, especially given that progression-free survival is significantly longer.”
Dr. Filippo Pietrantonio is head of the Gastrointestinal Oncology Unit at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy. He leads research focused on new treatments for colorectal and gastric cancers, as well as translational studies aimed at understanding resistance to targeted therapies, immunotherapy and novel agents.
Regarding safety, grade 3 (severe) or higher treatment-related side effects occurred in 45.3%, 34% and 45.1% of patients receiving Lumakras 960 mg plus Vectibix, Lumakras 240 mg plus Vectibix, and investigator's choice, respectively. The most common side effects (in 5% or more of patients) were dermatitis acneiform, hypomagnesemia and rash with Lumakras 960 mg plus Vectibix; hypomagnesemia and diarrhea with Lumakras 240 mg plus Vectibix; and neutropenia, anemia and hypertension with investigator's choice. Treatment-related grade 3 or higher hepatotoxicity occurred in 1.9%, 0% and 2% of patients receiving Lumakras 960 mg plus Vectibix, Lumakras 240 mg plus Vectibix, and investigator's choice, respectively. Side effect profiles across treatment arms were consistent with previous reports.
“This was the first phase 3 study of a KRAS-G12C inhibitor plus an EGFR inhibitor to show a significant prolongation in progression-free survival over standard therapies in chemorefractory metastatic colorectal cancer,” Pietrantonio wrote.
In this phase 3, open-label trial, researchers enrolled adults with metastatic colorectal cancer that carried a KRAS G12C mutation and had progressed after at least one prior treatment for advanced disease. Prior therapy had to include fluoropyrimidine, oxaliplatin and irinotecan unless side effects prevented it, in which case trifluridine-tipiracil or regorafenib could be used if approved.
A total of 160 patients were randomly assigned in equal groups to receive sotorasib 960 mg plus panitumumab (53 patients), sotorasib 240 mg plus panitumumab (53 patients) or investigator’s choice (54 patients). Patients in the standard treatment group were allowed to switch after the primary analysis. Although the study was not powered to detect a survival difference, overall survival was assessed as a secondary endpoint after about half the expected deaths had occurred. This report presents overall survival, updated response rates, and safety findings.
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