Osimertinib plus durvalumab versus osimertinib monotherapy in EGFR T790M-positive NSCLC following previous EGFR-TKI therapy: CAURAL brief report.

Osimertinib plus durvalumab versus osimertinib monotherapy in EGFR T790M-positive NSCLC following previous EGFR-TKI therapy: CAURAL brief report.

J Thorac Oncol. 2019 Feb 11;:

Authors: Chih-Hsin Yang J, Shepherd FA, Kim DW, Lee GW, Lee JS, Chang GC, Lee SS, Wei YF, Lee YG, Laus G, Collins B, Pisetzky F, Horn L

Abstract
INTRODUCTION: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Durvalumab is an anti-PD-L1 monoclonal antibody. The Phase III open-label CAURAL trial (NCT02454933) investigated osimertinib plus durvalumab versus osimertinib monotherapy in patients with EGFR-TKI sensitizing and T790M mutation-positive advanced non-small cell lung cancer (NSCLC) and disease progression following EGFR-TKI therapy.
METHODS: Patients were randomly assigned 1:1 to receive oral osimertinib (80 mg once daily) with/without durvalumab (10 mg/kg intravenously every two weeks), until progression. Treatment could continue beyond progression, providing clinical benefit continued (judged by investigator). The amended primary objective was to assess safety and tolerability of osimertinib plus durvalumab; efficacy was an exploratory objective.
RESULTS: CAURAL recruitment terminated early due to increased interstitial lung disease (ILD)-like events incidence in the osimertinib plus durvalumab arm from the separate Phase Ib TATTON trial (NCT02143466). At CAURAL recruitment termination, 15 patients had been randomly assigned to osimertinib and 14 to osimertinib plus durvalumab. Most common AEs (% [Grade ≥3]): diarrhea (53% [6%]) in the osimertinib arm; rash (67% [0]) in the combination arm. One patient randomized to the combination arm reported Grade 2 ILD while receiving osimertinib monotherapy (after discontinuing durvalumab following one dose). Objective response rates: 80% in the osimertinib arm; 64% in the combination arm.
CONCLUSION: Limited patient numbers preclude formal safety and efficacy comparisons between the two treatment arms. The combination of PD-1/PD-L1 inhibitors and EGFR-TKIs as therapy for NSCLC is not well understood, but requires a careful approach if considered in the future.

PMID: 30763730 [PubMed - as supplied by publisher]

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