Dr Parikh on the Impact of the ADAURA and ALINA Trials on Early-Stage NSCLC Management

Kaushal Parikh, MBBS, thoracic oncologist, assistant professor, oncology, Mayo Clinic, discusses how findings from the phase 3 ADAURA (NCT02511106) and ALINA (NCT03456076) trials have advanced treatment approaches in early-stage, resected non–small cell lung cancer (NSCLC) for patients harboring EGFR and ALK mutations.

The ADAURA trial evaluated the efficacy of osimertinib (Tagrisso) as an adjuvant therapy following surgery and chemotherapy in patients with stage IB to IIIA NSCLC with EGFR exon 19 or 21 mutations, Parikh begins. Adjuvant osimertinib significantly improved disease-free survival (DFS), with a median DFS of 65.8 months (95% CI, 61.7-not calculated) vs 28.1 months (95% CI, 22.1-35.0) with placebo (HR, 0.27; 95% CI, 0.21-0.34). Furthermore, the overall survival (OS) analysis of ADAURA showed a 5-year OS rate of 88% with osimertinib (n = 339) vs 78% with placebo (n = 343) in the overall population (HR, 0.49; 95.03% CI, 0.34-0.70; P < .001). These data showed the feasibility and efficacy of targeting EGFR mutations in the adjuvant setting for patients with early-stage, completely resected NSCLC, Parikh says.

Similarly, the ALINA trial investigated adjuvant alectinib (Alecensa) in patients with stage IB to IIIA NSCLC harboring ALK mutations, he details. Patients with stage IB to IIIA ALK-positive NSCLC,comprising the intention-to-treat (ITT) population, experienced a median DFS that was not reached with alectinib (n = 130) vs 41.3 months (95% CI, 28.5-not evaluable) with chemotherapy (n = 127). Moreover, alectinib reduced the risk of disease recurrence or death by 76% compared with chemotherapy (HR, 0.24; 95% CI, 0.13-0.43; P < .0001). These results supported the April 2024 FDA approval of alectinib as an adjuvant treatment after resection for this patient population.

Although both trials have significantly impacted clinical practice, there are notable differences between them, Parikh continues. In ADAURA, patients were randomly assigned to receive osimertinib or placebo after chemotherapy. Although chemotherapy was optional, it was administered to most patients, he says. In contrast, ALINA directly compared alectinib with chemotherapy, Parikh explains. Additionally, the durations of adjuvant therapy differed between the 2 trials; patients in ADAURA received osimertinib for 3 years, whereas patients in ALINA received alectinib for 2 years, he notes.

Overall, these practice-changing studies reinforce the need for routine EGFR and ALK mutation testing before administering immunotherapy in early-stage NSCLC, Parikh concludes.