Dr Yaeger on the Implications of Data With Second-Line Sotorasib Plus Panitumumab in mCRC

Rona Yaeger, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, discusses the future implications of findings from an expansion cohort study of sotorasib (Lumakras) plus panitumumab (Vectibix) in the second-line setting patients with KRAS G12C–mutated metastatic colorectal cancer (mCRC).

The expansion cohort study was based on findings from the phase 1b/2 CodeBreaK 101 trial (NCT04185883), in which sotorasib plus panitumumab elicited an overall response rate (ORR) of 30% when administered as second-line therapy.

Results presented during the 2024 Gastrointestinal Cancers Symposium showed that the combination elicited an observed ORR of 30% (n = 20; 95% CI, 11.9%-54.3%), comprised entirely of partial responses. Moreover, the regimen's adverse effect profile in this cohort study was comparable to safety data from prior studies of these agents.

Yaegar states that one of the most exciting findings in the study was the extended median progression-free survival (PFS) of 8.3 months (95% CI, 4.3-14.1), which may be attributed to the fact that patients were treated in the second-line setting. This finding indicates that initiating treatment earlier in the disease course could lead to longer-lasting responses before the tumor develops resistance to multiple therapies, even if response rates in the second-line setting are similar to those observed in later lines of therapy, Yaeger explains.

As of the end of 2023, KRAS G12C–targeted therapy has been incorporated into the National Comprehensive Cancer Network guidelines for CRC, Yaeger continues. The guidelines now include sotorasib, panitumumab, adagrasib (Krazati), and cetuximab (Erbitux) as recommended treatment options. There is hope that these drugs will receive regulatory approval in this indication, further expanding the therapeutic options available in CRC, she states.

Several new KRAS G12C inhibitors are also progressing through clinical development with promising data, offering the potential for additional treatment choices within the CRC treatment paradigm, Yaeger adds. However, the optimal sequencing of these agents remains unknown, highlighting the need for further research to determine the most effective treatment strategies for targeting KRAS-mutant CRC, Yaeger concludes.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.