Episode 10: ADAURA presents OS data on adjuvant osermitinib in EFGR-mutated NSCLC patients

In this episode of WND, Prof Johan Vansteenkiste from University Hospitals Leuven and Prof Mariana Brandao, a medical oncologist at Institut Jules Bordet in Brussels, present the highly anticipated OS results from the ADAURA trial.

The ADAURA trial focuses on patients with stage IB2, II and IIIA NSCLC harbouring classic EGFR mutations who underwent surgery, with optional chemotherapy, randomized between 3 years of adjuvant osimertinib or placebo until disease recurrence, completion of treatment, or meeting discontinuation criteria.

While the DFS data were positive and noteworthy, it’s acknowledged that previous trials with first-generation TKIs haven’t translated such benefits into OS. Hence, the eagerly awaited OS data, especially since osimertinib is also the first-line therapy for metastatic disease.

The ADAURA trial demonstrates an overall HR of 0.49, corresponding to a 51% reduction in the risk of progression or death with adjuvant osimertinib. Notably, the benefit increases with advanced disease stages, with stage III patients exhibiting an approximately 18% difference between osimertinib and placebo, implying a delay in progression as observed in DFS and decreasing the likelihood of death. A notable trial limitation is that only 40% of patients on the placebo arm later received osimertinib, depriving 60% of the current SOC in the first line.

Importantly, the 3-year regimen poses a challenge for patients, with long-term adherence issues. Understanding why patients discontinue treatment, even with low-grade toxicity, is pivotal as cumulative toxicity can significantly impact QoL.

Overall, the ADAURA study introduces a new SOC for patients with stage IB2, II and stage III NSCLC at high risk of relapse and death. It stands as the first trial providing OS data in this context, thus delivering a pertinent message.

The data from this trial, however, do not suggest that chemotherapy can be entirely omitted. It remains advisable to employ chemotherapy judiciously, considering its potential toxicity. If toxicity levels are deemed too high, osimertinib could serve as a viable alternative.

If postoperative reimbursement for osimertinib becomes the new SOC, in cases of relapse timing becomes paramount. If relapse occurs after discontinuation of the TKI, conducting a biopsy could elucidate any histological transformation, aiding in the comprehension of resistance mechanisms and facilitating optimal treatment selection moving forward. This underscores the importance of molecular biology restaging.