Safety and Efficacy Analysis of Patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC) Treated with SHR-1316 Plus Chemotherapy and Sequential Chest Radiotherapy as First-Line Therapy from a Phase II Trial

Abstract

CAPSTONE-1, a phase 3 trial, showed that SHR-1316 (PD-L1 antibody) combined with standard first-line chemotherapy could prolong overall survival (OS) in patients (pts) with ES-SCLC. The CREST trial reported consolidative thoracic radiotherapy (TRT) of 30 Gy in 10 fractions provided a 10% 2-year OS benefit and more intensive TRT should be investigated in ES-SCLC. In the era of immunotherapy, the role of TRT also needs further exploration. Therefore, we designed this clinical trial to investigate the efficacy and safety of SHR-1316 plus first-line chemotherapy followed by TRT combined with SHR-1316. Key inclusion criteria were pts aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC, and an ECOG performance status of 0-1. Eligible pts would receive 4∼6 cycles of SHR-1316 (20mg/kg, D1, q3w) combined with EP/EC (etoposide, 100mg/m2, D1-5, q3w and cisplatin, 75mg/m², D1-3, q3w or carboplatin, AUC = 5, D1, q3w), followed by SHR-1316 combined with TRT (≥3 Gy*10 f or ≥2 Gy*25 f, involved-field irradiation), and then the maintenance therapy with SHR-1316 until disease progression or intolerable adverse events (AEs). The main endpoints included ORR, PFS and safety. From October 2020 to January 2023, 33 pts received SHR-1316 and sequential consolidative TRT. Among them, 19 pts received high-dose TRT (>3 Gy*10 f or ≥2 Gy*25 f) and 14 pts received low-dose TRT (≤3 Gy*10 f or<2 Gy*25 f). The median age was 62 (range: 38-73). Most pts were male (28, 84.8%), former smokers (22, 66.7%) with an ECOG performance status 1 (32, 97%). Ten (30.3%) pts were diagnosed with brain metastasis and 10 (30.3%) pts had liver metastasis at baseline. At the data cutoff date, 9 pts remained on treatment, the average number of treatment cycles was 9.2. 33 pts had at least one 1 post-treatment tumor assessment. The confirmed ORR and DCR were 90.9% (30/33) and 100% (33/33) in all pts, were 89.5% (17/19) and 100% (19/19) in high-dose TRT group, and were 92.9% (13/14) and 100% (14/14) in low-dose TRT group. The median PFS was 10.2(CI: 5.8∼14.7) months in all pts, was 7 (CI: 3.8∼10.2) months in high-dose TRT group and 10.4 (CI: 8.4∼12.3) months in low-dose TRT group. AEs occurred in 27 (81.8%) pts and grade 3 or 4 AEs occurred in 20 (60.6%) pts. The most common grade 3 or 4 AEs included neutropenia (15, 45.5%), leukopenia (8, 24.2%), lymphocytopenia (5, 15.2%), pneumonia (3, 9.1%), anemia (3, 9.1%) and thrombocytopenia (2, 6.1%). SHR-1316 plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. There is no significant difference between high-dose and low-dose TRT groups in terms of safety and efficacy according to current data.