Durvalumab after sequential CRT safe in stage III, unresectable NSCLC

The first results of the phase 2 PACIFIC-6 trial showed that durvalumab after sequential chemoradiotherapy (CRT) has a similar safety profile to that of durvalumab after concurrent CRT.

In the phase 3, placebo-controlled PACIFIC trial (NCT02125461), durvalumab after concurrent CRT significantly improved progression-free survival (PFS) and overall survival (OS) in patients with stage III, unresectable non-small cell lung cancer (NSCLC) [1]. This benefit was maintained in the recent 5-year update [2]. However, as many patients are ineligible for concurrent CRT, the phase 2 PACIFIC-6 trial (NCT03693300) aimed to assess safety with durvalumab after sequential CRT.

In PACIFIC-6, patients with ECOG performance status (PS) ≤2 and no progression after platinum-based sequential CRT were enrolled to receive durvalumab for 24 months or until progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was safety/tolerability of durvalumab, defined by the incidence of grade 3/4 possibly treatment-related adverse events occurring within 6 months of treatment initiation. PFS, OS, and overall response rate (ORR) were secondary endpoints. Dr Marina Garassino (University of Chicago, IL, USA) reported the primary safety analysis and secondary efficacy analyses from PACIFIC-6 [3].

A total of 117 patients were enrolled; 37.6% had stage IIIA, 50.4% had stage IIIB, and 11.1% had stage IIIC NSCLC. The median age was 68.0 years, 62.4% were male, and most patients had ECOG PS 0/1 (97.4%); 98.3% had past/present medical conditions, mostly vascular (59.0%), respiratory (53.8%), or metabolic (51.3%) disorders. All participants received ≥1 dose of durvalumab. The median duration of treatment was 32.0 weeks. At data cut-off, 37.6% were still on treatment, 29.9% discontinued due to progression, 21.4% discontinued due to adverse events, 8.5% discontinued due to other reasons, and 2.6% of patients had completed treatment.

Overall, 94.9% of participants had any adverse events and 76.9% had possible treatment-related adverse events. Grade 3/4 adverse events were observed in 18.8% of participants, and grade 3/4 possible treatment-related adverse events were observed in 4.3%. In 21.4% and 16.2%, adverse events and possible treatment-related adverse events led to discontinuation of treatment, respectively.

The median PFS was 10.9 months in the full cohort, and 13.1 months in the PS 0/1 cohort. Median OS was 25.0 months for the full cohort and in the PS 0/1 cohort; ORR was 17.1% and 17.5%, respectively. Best response to sequential CRT was complete response (n=1), partial response (n=75), and stable disease (n=32).

In summary, durvalumab after sequential CRT had a similar safety profile to that observed with durvalumab after concurrent CRT in the PACIFIC trial and showed encouraging preliminary efficacy in a frailer and older population.

1. Antonia SJ, et al. N Engl J Med 2018; 379:2342–2350.
2. Spigel DR, et al. J Clin Oncol. 2022;40(12):1301–1311.
3. Garassino MC, et al. Safety and efficacy outcomes with durvalumab after sequential chemoradiotherapy (sCRT) in stage III, unresectable NSCLC (PACIFIC-6). Abstract 108MO. ELCC 2022 Virtual Meeting, 30 March–02 April.

 

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Posted on 25 May 202215 February 2024