Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations. (May 2022) - Riudavets, Mariona
Abstract: Introduction: Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised. Material and methods: Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR / BRAF / KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA. Results: Out of 323 patients included, 43 patients had one dGA: KRAS m (n = 26; 8 G12C), EGFR m (n = 8; 6 del19/ex21), BRAF m (n = 5; 4 V600E) and ALK r (n = 4). The median age was 66 years [39–84], gender ratio 1:1, with 98% performance status (PS) 0–1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2–24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4–28.3) ( P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRAS m G12C vs. 8.1 mo (5.8-NR) in the EGFR m del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAF m V600E/ ALK r ( P = 0.02). Conclusions: We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAF m and ALK r but not for those harbouring KRAS m. Larger prospective studies are needed to confirm these findings. Highlights: Similar treatment outcomes to PACIFIC phase III trial. Different benefits of durvalumab consolidation based on oncogenic alterations. Significant increase in PFS with durvalumab in patients with KRAS mutations. ALK- rearranged NSCLC seem to benefit the least to durvalumab consolidation. Largest retrospective study evaluating durvalumab in oncogenic addicted stage III NSCLC.