Hypofractionated radiotherapy with immunochemotherapy for extensive-stage small-cell lung cancer

Abstract

Introduction: The combination of a PD-L1 inhibitor plus carboplatin/cisplatin and etoposide (EC/EP) has become a new standard first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). Combining concurrent palliative hypofractionated radiotherapy of the thorax (HFRT) and immunochemotherapy may have a synergistic effect. In this study, we explored an optimal model of combination radiotherapy with immunochemotherapy as first-line treatment of ES-SCLC.

Patients and methods: In this multicenter single-arm phase 2 trial, patients with ES-SCLC received atezolizumab with EC/EP for two cycles (induction phase), then, those who did not progress received concurrent palliative HFRT and two cycles of atezolizumab with EC/EP (combination phase). Afterward they received atezolizumab every 3 weeks for a maximum of 2 years after study enrolment (maintenance phase). Prophylactic cranial irradiation (PCI) was recommended. The primary endpoints were safety and tolerance; the second endpoints were progression-free survival (PFS).

Results: Forty patients were enrolled, and all had completed palliative HFRT and four cycles of immunochemotherapy. There were seven grade 3 adverse events (3 decreased neutrophil count, 1 anemia, 2 pneumonitis, 1 esoenteritis), two grade 4 adverse events (2 decreased white cell count) and no grade 5 toxicities. The pneumonitis rate was 12.5% (three grade 2 and two grade 3 events). At the median follow-up of 14.2 months (range, 6.8-28.7), the median PFS was 8.6 months (95%CI, 6.1-11.1).

Conclusion: The addition of concurrent hypofractionated thoracic radiotherapy to first-line immunochemotherapy for ES-SCLC was well tolerated and showed promising clinical efficacy. Additional randomized trials are needed to validate benefits.

Clinical trial registration: https://clinicaltrials.gov/ (NCT04636762).

Keywords: extensive-stage small-cell lung cancer; immunochemotherapy; progression free survival; safety; thoracic radiation.

Figure 1

Flowchart showing study eligibility and analysis.

Figure 2

Kaplan–Meier plots of progression-free survival. The blue dot lines represent 95% CI of PFS.

Figure 3

Waterfall map showing the best response of enrolled patients. The waterfall plots display an individual patient’s best response data expressed as the percent change in the sum of the longest diameter of target lesions as measured at baseline and the best response during the whole treatment period. (SD, PR) is indicated by the color of the data bar. SD, stable disease; PR, partial response. The red dot line represents 20% increase in the sum of the longest diameter of target lesions than baseline according to RECIST 1.1. The green dot line represents 30% decrease in the sum of the longest diameter of target lesions than baseline according to RECIST 1.1.