Feasibility of consolidative immunotherapy and outcomes of chemoradiation for limited-stage small-cell lung cancer in the real world
Abstract
Small-cell lung cancer (SCLC) is an aggressive disease presenting with limited stage (LS) in approximately 25% of cases. This study characterized the routine management of LS-SCLC as a benchmark for the advent of immune checkpoint inhibitors (ICI). A retrospective real-world cohort study of 533 consecutive patients with histologically confirmed LS-SCLC treated at the Thoraxklinik between 01/2010-12/2019. Clinical characteristics were extracted from the patients’ records with reassessment of tumor response and progression according to RECIST v1.1 by the investigators. Of 533 patients, 418 (78.4%) received curative-intent treatment: definitive chemoradiation (CRT) in 392 patients (73.5%; sequential CRT in 303/392 [77.3%] and concurrent CRT in 89/392 [22.7%]), or surgery followed by adjuvant chemotherapy (n=16, 3.0%) or CRT (n=10, 1.9%). The remaining could receive only single-modality or no therapy with poor median overall survival (mOS) <6 months. Concurrent ( vs. sequential) CRT was associated with longer mOS (28.5 vs. 19.1 months, 34.7% vs. 16.3% at 5 years, p<0.001), which remained significant in multivariable testing (hazard ratio [HR] 0.75, p<0.05). Prophylactic cranial irradiation (PCI) was also associated with longer mOS (23.1 vs. 13.0 months, p<0.001, HR 0.59) and lower risk of intracranial relapse by 61% (p=0.003). The eligibility rate for durvalumab consolidation after concurrent CRT was 87.6% (95% confidence interval 79.0-93.7%), and after any CRT 69.4% (64.6-73.9%), which corresponded to 52.7% (48.3-57.0%) of all LS-SCLC patients. Main ICI contraindication was grade 2+ pneumonitis, which occurred in 10.8% at the end of RT and was more frequent after sequential compared to concurrent treatment (p=0.001). Definitive treatment was feasible for approximately 78% of LS-SCLC patients, while approximately 50% are estimated to be eligible for durvalumab post-CRT. Concurrent treatment and administration of PCI were independently associated with better outcomes, but the median OS <2 years in this real-world population underlines the urgent need for novel therapeutic options.