The combination of sotorasib and panitumumab outperformed researchers’ treatment of choice in a phase 3 trial in chemotherapy-resistant patients. classG12C– Mutant metastatic colorectal cancer (CRC).
Researchers tested the combination with two different doses of sotorasib and found that both doses improved progression-free survival (PFS). However, outcomes were better with higher doses of sotorasib.
“The combination of sotorasib 960 mg and panitumumab has the potential to become a new standard of care for previously treated patients. classG12C“It’s a mutated metastatic colorectal cancer,” said study researcher Filippo Pietrantonio, M.D., of the National Institute of Oncology Foundation IRCCS in Milan, Italy.
Continue reading
Dr. Pietrantonio is a member of the Phase 3 CodeBreak 300 study (ClinicalTrials.gov identifier: NCT05198934), at ESMO Congress 2023.
CodeBreak 300 enrolled 160 patients with the following symptoms: classG12C– Mutant metastatic CRC who has received at least one type of therapy and whose disease progressed during or after administration of fluoropyrimidine, irinotecan, and oxaliplatin.
Patients were randomly assigned to one of three treatment groups.
- Sotorasib 960 mg/day + panitumumab 6 mg/kg every 2 weeks (n=53)
- Sotorasib 240 mg/day + panitumumab 6 mg/kg every 2 weeks (n=53)
- Investigator choice of trifluridine/tipiracil or regorafenib (n=54).
Baseline characteristics were generally balanced between arms. Objective response rates were 26% in the sotorasib-panitumumab 960 mg group, 6% in the sotorasib-panitumumab 240 mg group, and 0% in the investigator’s choice group. Disease control rates were 72%, 68%, and 46%, respectively.
At a median follow-up of 7.8 months, the median PFS was:
- 2.2 months in investigator-selected treatment arm
- 3.9 months in the sotorasib-panitumumab 240 mg group (hazard ratio) [HR]0.58; 95% CI, 0.36-0.93; P =.030)
- sotorasib-5.6 months in the panitumumab 960 mg group (HR, 0.49; 95% CI, 0.30-0.80; P =.006).
Overall survival data were not mature at the time of data cutoff.
The incidence of grade 3 or higher treatment-related adverse events (TRAEs) was 36% in the 960 mg group, 30% in the 240 mg group, and 43% in the investigator-selected group. There were no fatal TRAEs in any arm.
The most common grade 3 or higher TRAEs with sotorasib and panitumumab were acneiform dermatitis, hypomagnesemia, rash, and diarrhea. The most common grade 3 or higher TRAEs in the investigator-selected treatment arm were neutropenia, nausea, and anemia.
Disclosure: This research was supported by Amgen. Some study authors declare affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a complete list of disclosures.
References
1. Pietrantonio F, Salvatore L, Esaki T, et al. Comparison of Sotorasib and Panitumumab Combination with Standard Treatment for Chemotherapy Resistance class G12C Mutant Metastatic Colorectal Cancer (mCRC): CodeBreak 300 Phase III Study. Presented at ESMO Congress 2023. October 20-24, 2023, Madrid, Spain. Abstract LBA10.
Fakih MG, Salvatore L, Esaki T, et al. Combination of sotorasib and panitumumab for mutated and refractory colorectal cancer class G12C. N English J Medicine. Published online October 22, 2023. doi:10.1056/NEJMoa2308795