Sutetinib produced responses in 71% of patients with uncommon EGFR mutations in a phase IIb trial

A 70.8% response rate on independent review

The independent review committee confirmed responses in 70.8% of the 96 efficacy-evaluable patients (95% confidence interval [CI], 60.7–79.7), and the disease control rate was 90.6% (95% CI, 82.9–95.6).

Responses lasted a median of 12.0 months (95% CI, 9.3–15.7). Median progression-free survival was 13.7 months (95% CI, 10.9–16.4). Median overall survival had not been reached at the October 2024 cut-off, and the lower bound of its confidence interval was 22.2 months.

The efficacy analysis took in every patient who received at least one dose and could be evaluated, which left three of the 99 enrolled patients outside it. The safety analysis covered all 99.

Higher response with compound than with single uncommon mutations

Patients with predefined compound mutations had an objective response rate of 84.4%, against 64.1% in those with a solitary uncommon mutation, and a median progression-free survival of 13.8 against 11.0 months. The authors describe the difference as numerical, and the abstract gives no statistical comparison between the two groups.

Uncommon mutations account for about 10% of EGFR-altered NSCLC, and their sensitivity to EGFR inhibitors differs from one alteration to the next. The authors note that prospective evidence to guide first-line therapy in this group has been limited. Afatinib’s US label was extended to G719X, S768I and L861Q in 2018 on a post hoc analysis of its earlier trials, so a prospective trial built around these mutations adds a different kind of evidence.

Diarrhoea led the grade 3 or higher adverse events

Almost every treated patient, 96 of 99 (97.0%), had a treatment-related adverse event of some grade, and 42 (42.4%) had one of grade 3 or higher.

Diarrhoea was the most common severe event, at 28.3% (28 of 99), followed by hypokalaemia at 8.1% and increased gamma-glutamyl transferase at 5.1%. Treatment-related adverse events led to a dose reduction in 34.3% of patients and to discontinuation in 4.0%. No treatment-related deaths occurred.

Dose reductions (34 patients) were more than eight times as common as discontinuations (4 patients), which suggests that the toxicity at 80 mg once daily was more often handled by lowering the dose than by stopping treatment.

“Sutetinib met the prespecified primary endpoint and demonstrated clinically meaningful antitumor activity with a manageable safety profile in advanced NSCLC harboring uncommon EGFR mutations (G719X, S768I, and L861Q).”Wu et al., Journal of Thoracic Oncology (2026)

No comparator arm and 16.6 months of median follow-up

With no control group, the 70.8% response rate and 13.7-month median progression-free survival cannot be compared directly with afatinib, osimertinib or chemotherapy in the same population.

The mutation mix matters for the same reason. Because compound mutations responded more often, the overall figures depend on what share of patients carried them, and a trial with a different mix could report a different overall rate.

Overall survival will need longer follow-up, since fewer than half of the patients had died by the data cut-off.