Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Another KRAS G12C inhibitor. Congrats to FCS Director of Drug Development Manish Patel, MD, one of the authors. Durable responses with less adverse events.
To verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC).
TRIPLETE was a prospective, open-label, phase III trial in which previously untreated patients with unresectable RAS and BRAF wt mCRC were randomly assigned 1:1 to modified FOLFOX/panitumumab (control group) or mFOLFOXIRI/panitumumab (experimental group) up to 12 cycles, followed by fluorouracil/-leucovorin/panitumumab until disease progression. The primary end point was objective response rate (ORR) according to RECIST 1.1. Hypothesizing an ORR of 60% in the control group, 432 cases provided 90% power to a two-sided chi-square test for heterogeneity with a two-sided alpha error of .05 to detect ≥ 15% differences between arms (ClinicalTrials.gov identifier: NCT03231722).
From September 2017 to September 2021, 435 patients were enrolled (control group/experimental group: 217/218) in 57 Italian sites. One hundred sixty (73%) patients treated with mFOLFOXIRI plus panitumumab and 165 (76%) patients treated with modified FOLFOX plus panitumumab achieved RECIST response (odds ratio 0.87, 95% CI, 0.56 to 1.34, P = .526). No differences in early tumor shrinkage rate (57%/58%, P = .878) and deepness of response (median: 48%/47%, P = .845) were reported, nor in R0 resection rate (25%/29%, P = .317). No significant difference between arms was reported in terms of progression-free survival (median progression-free survival: 12.7 in the experimental group v 12.3 months in the control group, hazard ratio: 0.88, 95% CI, 0.70 to 1.11, P = .277).
The intensification of the upfront chemotherapy backbone in combination with panitumumab does not provide additional benefit in terms of treatment activity at the price of increased gastrointestinal toxicity in patients with RAS and BRAF wt mCRC.
Another KRAS G12C inhibitor. Congrats to FCS Director of Drug Development Manish Patel, MD, one of the authors. Durable responses with less adverse events.
If anti PD-L1 was not used as first line treatment, this study shows you can still use it as second line.
In this study, Cetuximab beat Bevacizumab in left sided KRAS wild type colon cancer.
Guideline of the month — ASCO guidance on mCRC. Many interesting points made.
In the SUNLIGHT study, Lonsurf + bevacizumab was found to be superior to bevacizumab alone in the 3L setting of mCRC, independent of mutation status. First 3L mCRC where the control group was an active compound instead of a placebo. OS was superior, with a clinically meaningful difference of 10.8 vs. 7.5 months. This is now the SOC 3L option in mCRC, in my opinion.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
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