medwireNews: The KRAS G12C inhibitor sotorasib has durable efficacy and manageable safety in previously treated patients with KRAS-mutated, advanced non-small-cell lung cancer (NSCLC), suggests long-term follow-up of the CodeBreaK 100 trial.
At a median follow-up of 24.9 months, “the longest follow-up of patients on any KRAS G12C inhibitor,” the 2-year overall survival (OS) rate was 32.5%, “which compares very favorably to what we would expect with historical treatment using docetaxel in this setting,” presenter Grace Dy (Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA) told delegates of the AACR Annual Meeting 2022 in New Orleans, Louisiana, USA.
Dy noted that the primary analysis of the phase 1/2 study led to approval of sotorasib in the USA and other countries for pretreated NSCLC positive for KRAS G12C mutations.
The current presentation focused on a pooled analysis of data from 174 patients with locally advanced or metastatic NSCLC who received the approved 960 mg/day dose of sotorasib in the phase 1 and 2 parts of the trial. Participants were aged a mean of 64.1 years, and the majority (82.8%) had previously received platinum-based chemotherapy as well as anti-PD-1 pathway therapy.
As reported by Dy, the overall response rate among the 172 evaluable patients was 40.7% and the disease control rate was 83.7%. Responses lasted for a median of 12.3 months, and half (50.6%) of responders had an ongoing response for more than 12 months.
The median progression-free survival (PFS) and OS times were similar to those in the primary analysis, at 6.3 and 12.5 months, she said.
The researchers conducted biomarker analysis in patients with available data, finding that long-term benefit with sotorasib (defined as PFS ≥12 months) was observed across PD-L1 expression levels. Specifically, 51.6% of the 31 patients with low PD-L1 levels (<1%) derived a long-term benefit, as did 28.6% of the 21 with intermediate levels (1–49%) and 25.0% of the four with high expression (≥50%).
Treatment with sotorasib also offered long-term benefit to patients with STK11 co-mutations, provided KEAP1 was wild-type, with long-term benefit rates of 46.2% among the 13 patients with STK11 mutations and 45.5% among the 33 with wild-type STK11. By contrast, in the subgroup with KEAP1 mutations, 16.7% of the 12 participants with STK11 mutations and 14.3% of the seven with wild-type STK11 derived a long-term benefit.
Sotorasib appeared to be “[w]ell tolerated in the long term,” and late-onset treatment-related adverse events (TRAEs) “were mild and manageable,” said the presenter.
Overall, TRAEs of grade 3 or 4 occurred in 21% of patients, but there was only one new-onset TRAE of grade 3 after 1 year, a case of hemolytic anemia. There were no discontinuations due to TRAEs after a year and no fatal TRAEs.
“There is no cumulative toxicity, nor delayed onset of side effects, in contrast to what we would expect with traditional chemotherapy or immunotherapies,” commented Dy.
She highlighted in a press release that the phase 3 CodeBreaK 200 study, which includes docetaxel as the comparator, is ongoing.
And Dy concluded: “We eagerly await the results of the phase III study, which likely will be available later this year, and expect that they will confirm our findings from CodeBreaK 100.”
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AACR Annual Meeting 2022; New Orleans, Louisiana, USA: 8–13 April