Osimertinib after CRT safe, effective in unresectable stage III EGFR-mutated NSCLC

Treatment with osimertinib following definitive chemoradiotherapy (CRT) demonstrates a manageable safety profile in patients with unresectable stage III EGFR-mutated nonsmall cell lung cancer (NSCLC), reports a study presented at WCLC 2024.

Most adverse events (AEs) associated with osimertinib, such as diarrhoea and rash, are mild or moderate in severity, and none has led to discontinuation.

“These safety data, together with efficacy data, support osimertinib given after definitive CRT as the new standard of care for patients with unresectable stage III EGFR-mutated NSCLC,” said lead author Dr Terufumi Kato, Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.

In the phase III LAURA study, osimertinib significantly improved progression-free survival in this population without progression during or after CRT (hazard ratio, 0.16, 95 percent confidence interval, 0.10‒0.24; p<0.001). [N Engl J Med 2024;391:585-597]

Here, Kato and his team reported an in-depth analysis from LAURA regarding the safety of osimertinib. They randomized 216 patients to receive osimertinib 80 mg (n=143) or placebo (n=73) QD until disease progression or discontinuation. Open-label osimertinib was offered in both arms after progression.

Kato and colleagues assessed safety at baseline, weeks 2, 4, and every 4 weeks thereafter until week 24, every 8 weeks until week 48, then every 12 weeks until treatment cessation.

Baseline characteristics were generally well balanced in both arms, and the median total and actual exposures were similar (total vs actual: osimertinib 24.0 and placebo 8.3 months vs 23.7 and 7.9 months, respectively). [WCLC 2024, abstract OA12.03]

The incidence of any-cause grade ≥3 and serious AEs was 35 percent and 38 percent with osimertinib compared with 12 percent and 15 percent with placebo, respectively. Moreover, the rates of exposure-adjusted grade ≥3 and serious AEs were comparable between arms: 17.7 and 19.5 per 100 patient-years with osimertinib vs 12.6 and 15.4 per 100 patient-years with placebo, respectively.

Pneumonitis

The most frequently reported AEs were radiation pneumonitis (RP; osimertinib 48 percent, placebo 38 percent), diarrhoea (osimertinib 36 percent, placebo 14 percent), and rash (osimertinib 24 percent, placebo 14 percent). RP was also the most common AE leading to treatment interruption (osimertinib 32 percent, placebo 14 percent) and discontinuation (osimertinib 5 percent, placebo 3 percent).

Of the 69 osimertinib-treated patients with RP, 22 (32 percent) continued treatment without dose modification, 43 (62 percent) interrupted treatment and restarted subsequently, and four (6 percent) discontinued permanently. Sixty patients (87 percent) continued osimertinib with no RP recurrence.

In addition, 11 of 143 (8 percent) osimertinib-treated patients reported developing interstitial lung disease (ILD). Of these, four (3 percent) had grade 1, four (3 percent) grade 2, two (1 percent) grade 3, and one (<1 percent) grade 5 severity.

“The types of side effects experienced, along with the significant benefit in progression-free survival, support using osimertinib after CRT as an effective treatment for patients with unresectable stage III EGFR-mutated NSCLC,” Kato said.