No impact of adjuvant chemotherapy use on the benefit of adjuvant osimertinib in patients with resected EGFR mutated NSCLC

Previously, the phase III ADAURA trial demonstrated that adjuvant osimertinib induces a highly significant benefit in disease free survival compared to placebo in patients with resected EGFR mutant NSCLC. An exploratory analysis of this trial now shows that this benefit is seen irrespective of the use of adjuvant platinum-based chemotherapy after the surgical resection.

Introduction

Approximately 30% of patients with non-small cell lung cancer (NSCLC) present with resectable disease at diagnosis and surgery with curative intent is the treatment for these patients. Following the surgery, adjuvant cisplatin-based chemotherapy is recommended for patients with resected stage II or IIIA NSCLC and can also be considered in patients with stage IB disease. However, rates of disease recurrence following surgery remain high across disease stages, regardless of postoperative chemotherapy use. In an attempt to improve these outcomes, the phase III ADAURA study assessed the impact of adjuvant osimertinib (a third-generation EGFR-TKI) in this setting. Previously, this trial demonstrated that adjuvant osimertinib was associated with a statistically significant and clinically meaningful improvement in disease free survival (DFS; HR[99.12%CI]: 0.20[0.14, 0.30]; p< 0.0001) in patients with resectable (stage IB-IIIA) EGFR-mutant NSCLC. In this trial, adjuvant chemotherapy use was allowed per physician’s choice and consisted of a platinum-based doublet for ≤4 cycles. During WCLC 2020, results of an exploratory analysis were presented looking into the benefit of osimertinib in function of adjuvant chemotherapy use.

Similar DFS benefit, irrespective of adjuvant chemotherapy use

Overall, 410 of the 682 (60%) patients enrolled in the study received adjuvant chemotherapy, for a median duration of 4 cycles. For almost all patients (409/410) the adjuvant chemotherapy was platinum-based and the majority (76%) of patients in the adjuvant chemotherapy cohort had stage II/IIIA disease. Furthermore, adjuvant chemotherapy was used more frequently in patients aged <70 years and in patients enrolled in Asia.

The benefit of osimertinib compared to placebo was not influenced by the use of adjuvant chemotherapy in this trial. Among patients who did receive adjuvant chemotherapy, the risk of disease progression was reduced by 84% for patients who received osimertinib compared to placebo (HR[95%CI]: 0.16[0.10-0.26]). At 24-months this translated into a DFS rate of 89% for patients in the osimertinib arm as compared to 49% in the placebo. Similarly, in patients who did not receive adjuvant chemotherapy, the use of osimertinib induced a 77% reduction in the risk of disease recurrence (HR[95%CI]: 0.23[0.13-0.40]) with 24-month DFS rates of 89% and 58%, respectively. Disease stage did not have an influence on these results.

Conclusion

The DFS benefit obtained from adjuvant osimertinib vs. placebo was observed irrespective of whether patients received prior adjuvant chemotherapy or not. These findings further support the use of adjuvant osimertinib in patients with stage IB/II/IIIA EGFR-mutant NSCLC after resection, with or without adjuvant chemotherapy.

Reference

Wu Y-L, et al. Postoperative chemotherapy use and outcomes from ADAURA: Osimertinib as adjuvant therapy for resected EGFR mutated NSCLC. Presented at WCLC 2020; Abstract OA06.04.