Sotorasib-panitumumab combo shows positive OS trend in mCRC

The combination regimen comprising sotorasib and panitumumab demonstrates a trend towards an improvement in overall survival (OS) compared with investigator’s choice of therapy among patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC) who had progressed on systemic therapy, according to the OS analysis of the CodeBreak 300 trial presented at ASCO 2024.

In the primary analysis, the combination regimen exhibited superiority over the investigator’s choice of therapy in terms of progression-free survival (PFS). However, the OS data were still immature at the time, according to lead author Dr Marwan Fakih from the City of Hope Comprehensive Cancer Center in Duarte, California, US.

This phase III trial involved 160 patients with KRAS G12C-mutated mCRC. Participants were randomized to receive sotorasib 960 mg (n=53) or 240 mg (n=53) once daily in addition to panitumumab 6 mg/kg every 2 weeks or investigator’s choice of therapy (n=54; trifluridine/tipiracil or regorafenib).

The key secondary endpoints of the study were OS and overall response rate (ORR). Fakih noted that this OS analysis was performed at 50-percent maturity and not powered for superior statistical significance.

At a median follow-up of 13.6 months, median OS was not reached in the sotorasib 960-mg plus panitumumab arm and 10.3 months in the investigator’s choice arm (hazard ratio [HR], 0.70), which translated to a 30-percent reduction in the risk of death. However, the difference between study arms was not statistically significant. [ASCO 2024, abstract LBA3510]

In the cohort of patients who received sotorasib 240 mg plus panitumumab, median OS was 11.9 months vs 10.3 months in the comparator arm (HR, 0.83).

In addition, fewer patients in the sotorasib plus panitumumab arm received subsequent anticancer treatment compared with those who were receiving the investigator’s choice of therapy (43 percent [960 mg] and 51 percent [240 mg] vs 61 percent).

The updated ORR was higher with sotorasib-panitumumab combination vs investigator’s choice of therapy (30 percent [960 mg] and 8 percent [240 mg] vs 2 percent), with a median duration of response of 10.1 months observed in the 960-mg sotorasib arm.

As per the blinded independent central review, median PFS was longer with sotorasib-panitumumab combo vs investigator’s choice of therapy (5.8 [960 mg] and 4 [240 mg] vs 2 months).

There were no new safety concerns, according to Fakih.

New standard of care?

“While CodeBreaK 300 was not powered to detect a statistically significant difference in OS, the study showed a [more favourable OS] trend among patients randomized to sotorasib 960 mg plus panitumumab,” said Fakih.