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.
Treatment of Metastatic Colorectal Cancer: ASCO Guideline
Author(s): Van K. Morris, MD1;Erin B. Kennedy, MHSc2;Nancy N. Baxter, MD, PhD3;Al B. Benson III, MD4;Andrea Cercek, MD5;May Cho, MD6;Kristen K. Ciombor, MD, MSCI7;Chiara Cremolini, MD, PhD8;Anjee Davis, MPPA9;Dustin A. Deming, MD10;Marwan G. Fakih, MD11;Sepideh Gholami, MD12;Theodore S. Hong, MD13;Ishmael Jaiyesimi, DO14;Kelsey Klute, MD15;Christopher Lieu, MD16;Hanna Sanoff, MD, MPH17;John H. Strickler, MD18;Sarah White, MD19;Jason A. Willis, MD, PhD1;and Cathy Eng, MD7
Source: DOI: 10.1200/JCO.22.01690 Journal of Clinical Oncology 41, no. 3 (January 20, 2023) 678-700.
Dr. Anjan Patel's Thoughts
Guideline of the month — ASCO guidance on mCRC. Many interesting points made.
PURPOSE
To develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC).
METHODS
ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.
RESULTS
Five systematic reviews and 10 randomized controlled trials met the systematic review inclusion criteria.
RECOMMENDATIONS
Doublet chemotherapy should be offered, or triplet therapy may be offered to patients with previously untreated, initially unresectable mCRC, on the basis of included studies of chemotherapy in combination with anti–vascular endothelial growth factor antibodies. In the first-line setting, pembrolizumab is recommended for patients with mCRC and microsatellite instability-high or deficient mismatch repair tumors; chemotherapy and anti–epidermal growth factor receptor therapy is recommended for microsatellite stable or proficient mismatch repair left-sided treatment-naive RAS wild-type mCRC; chemotherapy and anti–vascular endothelial growth factor therapy is recommended for microsatellite stable or proficient mismatch repair RAS wild-type right-sided mCRC. Encorafenib plus cetuximab is recommended for patients with previously treated BRAF V600E–mutant mCRC that has progressed after at least one previous line of therapy. Cytoreductive surgery plus systemic chemotherapy may be recommended for selected patients with colorectal peritoneal metastases; however, the addition of hyperthermic intraperitoneal chemotherapy is not recommended. Stereotactic body radiation therapy may be recommended following systemic therapy for patients with oligometastases of the liver who are not considered candidates for resection. Selective internal radiation therapy is not routinely recommended for patients with unilobar or bilobar metastases of the liver. Perioperative chemotherapy or surgery alone should be offered to patients with mCRC who are candidates for potentially curative resection of liver metastases. Multidisciplinary team management and shared decision making are recommended. Qualifying statements with further details related to implementation of guideline recommendations are also included.
Author Affiliations
1University of Texas MD Anderson Cancer Center, Houston, TX; 2American Society of Clinical Oncology, Alexandria, VA; 3Melbourne School of Population and Public Health, Melbourne, Australia; 4Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; 5Memorial Sloan Kettering Cancer Center, New York, NY; 6UCI Health, Irvine, CA; 7Vanderbilt Ingram Cancer Center, Nashville, TN; 8University of Pisa, Pisa, Italy; 9Fight Colorectal Cancer, Springfield, MO; 10University of Wisconsin Carbone Cancer Center, Madison, WI; 11City of Hope Helford Clinical Research Hospital, Duarte, CA; 12UC Davis Health, Davis, CA; 13Massachusetts General Hospital, Boston, MA; 14Beaumont Hospital, Royal Oak, MI; 15University of Nebraska, Omaha, NE; 16CU Medicine, Denver, CO; 17University of North Carolina, Chapel Hill, NC; 18University Medical Center, Durham, NC; 19Medical College of Wisconsin, Milwaukee, WIRelated Articles
Avelumab vs Standard Second-Line Chemotherapy in Patients With Metastatic Colorectal Cancer and Microsatellite Instability
If anti PD-L1 was not used as first line treatment, this study shows you can still use it as second line.
Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer
In this study, Cetuximab beat Bevacizumab in left sided KRAS wild type colon cancer.
Trifluridine/tipiracil plus bevacizumab for third-line treatment of refractory metastatic colorectal cancer: The phase 3 randomized SUNLIGHT study.
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.
Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO
Interesting lack of deepened response with chemotherapy intensification. Expected increase in GI toxicity, increased cost and diminished options upon progression place this truly a quadruple combination on the shelf.
