No improved prognosis for concurrent versus sequential immune checkpoint inhibition and CRT in unresectable NSCLC

In a prospective study, concurrent immune checkpoint inhibition did not improve prognosis in patients with unresectable non-small cell lung cancer (NSCLC), neither in progression-free survival (PFS) nor overall survival (OS), compared with sequential immunotherapy.

In patients with unresectable NSCLC, maintenance therapy with the immune checkpoint inhibitor durvalumab after completion of concurrent chemoradiotherapy (CRT), significantly improves PFS and 5-year OS [1,2]. In addition, results from the phase 2 NICOLAS trial (NCT02434081) suggested that concurrent administration of immune checkpoint inhibition (nivolumab) with CRT may improve the response rate over sequential therapy [3]. Dr Lukas Käsmann (University Hospital Munich, Germany) presented the results of a prospective, phase 3 study comparing the impact of concurrent versus sequential immune checkpoint inhibition and CRT in patients with unresectable NSCLC [4].

A total of 39 patients with unresectable, stage IIIA–C NSCLC were prospectively enrolled, of whom 38 (97.4%) received platinum-based concurrent CRT with curative intent (≥60 Gy). Concurrent CRT and immune checkpoint inhibition (nivolumab up to 1 year after the end of CRT) was administered to 11 participants (28.2%; SIM-I cohort). Sequential CRT and immune checkpoint inhibition with durvalumab was administered to 28 participants (71.8%; SEQ-I cohort). The median follow-up of the overall cohort, SIM-I cohort, and SEQ-I cohort was 27.2 months, 33.3 months, and 24.7 months after the end of CRT, respectively.

In the SEQ-I cohort, median PFS and OS were not reached. PFS rate in the SEQ-I cohort at 12 and 24 months was 63% and 59%, respectively. In the SIM-I cohort, median PFS was 22.8 months and median OS was not reached. PFS rate in the SIM-I cohort at 12 and 24 months was 82% and 44%, respectively.

Regarding safety, 18.2% of participants in the SIM-I cohort showed grade 3 radiogenic pneumonitis versus 14.3% in the SEQ- I cohort (P=0.765). Grade 4 and 5 toxicities did not occur.

Based on these results, Dr Käsmann concluded that concurrent immune checkpoint inhibition did not improve prognosis compared with sequential immunotherapy. Both approaches show a favourable side effect profile and promising results in patients with unresectable stage III NSCLC. A study limitation is the low number of participants.

1. Antonia SJ, et al. N Engl J Med 2017;377:1919–1929.
2. Spigel DR, et al. J Clin Oncol. 2022;40(12):1301–1311.
3. Peters S, et al. J Thorac Oncol 2021;16:278–288.
4. Käsmann L. et al. Concurrent versus sequential immune checkpoint inhibition in stage III NSCLC patients treated with chemoradiation. Abstract 115P. ELCC 2022 Virtual Meeting, 30 March–02 April.

 

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Posted on 25 May 202215 February 2024