As long as patients have good performance status, advanced age may not limit the efficacy of adagrasib in treating KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC), according to phase II study results presented at the European Lung Cancer Congress 2026.

The study, ETOP-ADEPPT, found that among patients aged 70 years or older with good performance status, 31% had a confirmed objective response to treatment with adagrasib, a second-generation KRAS G12C inhibitor.

In contrast, the drug showed limited efficacy for patients of any age who had poor performance status, suggesting that patients’ functioning, not age, is a key determinant of treatment response.

Around 15% of patients with NSCLC harbor KRAS G12C mutations. Adagrasib has been shown to improve progression-free survival among patients with previously treated disease compared with docetaxel. But elderly patients and those with poorer performance status — who account for a large proportion of patients with KRAS G12C-mutated NSCLC — are underrepresented in trials.

ETOP-ADEPPT aimed to assess the efficacy, safety, and impact on quality of life of adagrasib in those two patient populations.

The study enrolled two cohorts: Cohort A included 32 patients aged 70 years or older (median age, 76 years) with good performance status (ECOG PS 0 or 1), whereas cohort B included 34 patients (median age, 64 years) with reduced performance status (ECOG PS 2).

All patients received adagrasib until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response at 12 weeks; secondary endpoints included progression-free and overall survival, adverse events, and quality of life (measured by the National Comprehensive Cancer Network - Functional Assessment of Cancer Therapy Lung Symptom Index-17).

Cohort A met the primary endpoint, with 10 of 32 patients (31%) achieving confirmed objective responses, reported lead investigator Jarushka Naidoo, MD, medical oncologist at Beaumont Hospital in Dublin, Ireland.

Cohort B, however, did not meet the endpoint, with 6 of 34 patients (18%) achieving an objective response.

Cohort A patients also fared better in terms of survival outcomes, with a median progression-free survival of 7.6 months and overall survival of 9.5 months compared with 2.7 months and 4.3 months, respectively, in cohort B. Quality of life, however, improved in both cohort A and B, among the 18 and 11 patients, respectively, who were still on treatment at week 12.

As for safety, 41% of patients in cohort A had a treatment-related adverse event of grade 3 or higher, as did 62% of patients in cohort B. The most common side effects in both groups included diarrhea, nausea, vomiting, and fatigue.

The findings are in line with a body of research showing that chronological age is a poor surrogate for physiologic reserve and that geriatric assessment can help identify patients likely to struggle with cancer treatment.

Those points were highlighted by study discussant Silvia Novello, MD, PhD, of the University of Turin and San Luigi Hospital in Orbassano, Italy.

She said that age alone should not be considered a limiting factor in selection for treatment with adagrasib, but comprehensive geriatric assessment, close monitoring of toxicities, and caregiver involvement are necessary in these patients.

Naidoo and Novello reported financial relationships with several pharmaceutical companies.