Phase II Study of Sintilimab Combined with Concurrent Chemoradiotherapy in Patients with Limited-Stage Small Cell Lung Cancer (SINCE-01 Trial)

Abstract

<h3>Purpose/Objective(s)</h3> Sequent or concurrent chemoradiotherapy (CRT) is the standard of care for most patients with Limited-Stage Small Cell Lung Cancer (LS-SCLC). In the era of immunotherapy, we conducted this single-arm phase II study to test the hypothesis that CRT combined with PD-1 checkpoint inhibitor (Sintilimab) would improve the outcomes of patients with LS-SCLC. <h3>Materials/Methods</h3> Patients received sintilimab combined with concurrent CRT as follows: The chemotherapy regimen was etoposide (100 mg/m2 D1-3) and carboplatin (AUC=5 D1) once every 3 weeks for a total of 4 to 6 cycles. Sintilimab (200 mg once every 3weeks) was administered with chemotherapy. 1-2 cycles of induction chemotherapy combined with sintilimab before concurrent CRT were allowed. Residual-field irradiation (RFI) was adopted in the study: The gross tumor volume (GTV) defined as residual volumes of positive node and primary tumor of the post-chemotherapy. The clinical target volume (CTV) included GTV with a margin 0.5 cm. Planning target volume (PTV) involved CTV with a margin 0.5 cm. RFI consisted of 1.5 grays (Gy) twice daily in 30 fractions up to a total dose of 45 Gy or 2.0 Gy daily up to 60 Gy. Prophylactic cranial irradiation (PCI) was proposed ed to patients who attained a complete or partial response after CRT. The primary end points were progression-free survival (PFS) and objective response rate (ORR). Secondary outcomes were safety, tolerability and overall survival (OS). <h3>Results</h3> A total of 23 patients were screened, and 21 were enrolled. All patients completed concurrent CRT with sintilimab. Induction chemotherapy was given to 17 patients, and 16 received PCI, and the median cycles of sintilimab was 11 (range, 5-16). The median follow-up time was 10.3 months (range, 3.6-13.7months). And up till now, the median PFS has not yet been achieved. The 6-month and 1-year PFS rates were 84.2% and 78.9%, respectively. The 6-month and 1-year OS rates were 100% and 94.4%. Of the enrolled patients, 7 patients had a complete response, and 10 patients had partial responses, resulting in an ORR of 80.9%. A total of 4 patients had relapse, including 1 failure located in the supraclavicular regions, and 3 patients had metastasis (2 in the brain and 1 in the adrenal gland). No infield recurrence was noted. There were no grade 5 toxicities, but there were three grade 4 events (two neutropenia and one thrombocytopenia). And the median V20 Gy of double lungs in these patients was 13.0% (range, 7.0%-25.0%). Because RFI was adopted, the pneumonitis rate was as low as 14% (two grade 1 and two grade 2). All 6 radiation esophagitis events (28.6%) were grades 1 to 2. No unexpected toxicities were observed. <h3>Conclusion</h3> Preliminary study showed that sintilimab combined with concurrent CRT was well tolerated in the treatment of LS-SCLC. The initial results were very encouraging and the final outcomes are worth looking forward to. This provides a basis for the next phase III study of PD-1 checkpoint inhibitor combined with concurrent CRT in patients with LS-SCLC.