Real-world outcomes of PD-L1 inhibitors combined with thoracic radiotherapy in the first-line treatment of extensive stage small cell lung cancer

Abstract

Background The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival rate in patients with extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy remains controversial. This study aimed to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. Methods The patients who received durvalumab or atezolizumab combined with chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were enrolled. They were divided into two groups, based on whether they received TRT or not. Propensity score matching (PSM) with a 1:1 ratio was performed. The primary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 57 pairs of patients were enrolled in the analysis. In all patients, the median PFS (mPFS) in the TRT and non-TRT group was 9.5 and 7.2 months, respectively, with HR = 0.59 (95%CI 0.39–0.88, p = 0.009). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95%CI 0.31–0.89, p = 0.016). Multivariable analysis showed that baseline liver metastasis and the number of metastases ≥ 3 were independent prognostic factors for OS. Addition of TRT increased the incidence of treatment-related pneumonia (p = 0.018), most of which were grade 1–2. Conclusions Addition of TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. Although it may leads to increased incidence of treatment-related pneumonia, a majority of the cases can be relieved after symptomatic treatment.

Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy

“…Accordingly, survival improvement was noted in a more extensive cohort in a study by Peng et al. ( 14 ) that included 70 patients treated with TRT. In particular, median PFS and OS were significantly longer in patients who received TRT compared to those who did not, with median PFS of 9.5 months and 7.2 months, respectively, (hazard ratio (HR) of 0.59; p=0.009) and median OS of 24.1 months and 18.5 months, respectively (HR=0.53; p=0.016).…”

“…Only Peng et al. ( 14 ) described higher rates of treatment-related pneumonitis of 35.1% and 15.8% in the TRT and non-TRT groups (p=0.018), respectively, including one death due to immune checkpoint inhibitors related pneumonitis. In the present study, pneumonitis occurred in four (6.5%) and two (3.4%) patients in the TRT and non-TRT group, respectively.…”

“…However, recent chemoimmunotherapy trials have not explored this therapeutic approach. Preliminary data show a favorable safety profile and prognosis improvement in ES-SCLC patients receiving first-line PD-L1 inhibitors combined with chemotherapy ( 13 , 14 ). In accordance, current ASTRO, ASCO, and a recent Canadian consensus express a favorable opinion concerning TRT, especially in patients with residual mediastinal tumors and low extra-thoracic burden ( 15 , 16 ).…”

Real-world impact of the introduction of chemo-immunotherapy in extended small cell lung cancer: a multicentric analysis

“…We can speculate that the attitude might be mainly related to increased depth of responses induced by chemo-immunotherapy. The role of consolidation thoracic radiotherapy in extended SCLC has been demonstrated in CREST study and some data already exist concerning its role in patients treated with chemo-immunotherapy, although increased incidence of treatment-related pneumonitis is observed ( 27 – 30 ). Pneumonitis observed in patients treated sequentially seem to be mainly slightly symptomatic and manageable, while TREASURE study of concomitant atezolizumab plus consolidation radiotherapy was closed permanently due to safety alert related mainly to severe pneumonitis, including treatment-related deaths ( 27 , 31 ).…”

Treatment patterns and clinical outcomes in 157 patients with extensive-stage small cell lung cancer: real-world evidence from a single-center retrospective study

“…However, no conclusion was reached regarding ES-SCLC. Some studies thought ICIs plus radiotherapy could prolong survival ( 36 , 37 ), but the toxicity caused by radiation plus ICIs can limit this function ( 38 ).…”