Induction Therapy With PD-L1 Inhibitor TQB2450 + Chemotherapy Followed by Surgery or Radiotherapy in Limited-Stage SCLC

Based on improvements in survival outcomes with a PD-1/PD-L1 inhibitor in combination with chemotherapy in patients with extensive-stage small cell lung cancer (SCLC), a nonrandomized, single-center, phase 2 study (LungMate-005; NCT04539977) was conducted to explore the clinical safety and efficacy of neoadjuvant PD-L1 inhibitor TQB2450 plus chemotherapy induction therapy followed by surgery or radiotherapy in patients with limited-stage small-cell lung cancer (LS-SCLC).

Eligible patients had previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 or 1, and no active, known, or suspected autoimmune disease. Patients received four 21-day cycles of neoadjuvant therapy consisting of TQB2450 (1200 mg) and carboplatin (area under the curve of 5) on day 1 and etoposide (100 mg/m²) on days 1 to 3. Surgery or radiotherapy was discussed 3 to 4 weeks after last dose of induction therapy. Maintenance therapy was 2 cycles of TQB2450, carboplatin, and etoposide followed by TQB2450 for 1 year. The primary outcome was objective response rate (ORR); secondary outcomes included the incidence of adverse events (AEs), event-free survival (EFS), and major pathological response (MPR). Date of data cutoff was April 21, 2023.

A total of 40 patients received induction therapy between December 2020 and January 2023. Of these, 21 patients received surgery and 14 patients received radiotherapy. The median age was 61 years; the majority (95%) of patients had stage III disease, were smokers (70%), were male (87.5%), and had no PD-L1 expression (55%).

Grade 3-4 AEs were reported in 47.5% of patients with no reported deaths. Treatment-related adverse events (TRAEs) leading to discontinuation occurred in 3 (7.5%) patients. Most TRAEs were related to chemotherapy; the most common TQB2450-specific AE was rash (12.5%), which was of grade 1-2 severity. Five patients in the radiotherapy group developed pneumonitis and 4 patients in the surgery group had postoperative complications.

In the total population of 40 evaluable patients, ORR was achieved by 92.5% of patients; 13 (61.9%) patients achieved MPR, including 9 (42.9%) patients with pathological complete response. Pathological downstaging after surgery was reported in 17 (81.0%) patients. At a median follow-up of 14.8 months, median EFS and median overall survival (OS) were not reached in the surgery group, whereas the median EFS was 11.6 months and median OS was 18.6 months in the radiotherapy group.

Based on these data, neoadjuvant therapy with TQB2450 and chemotherapy induction therapy followed by surgery or radiation and TQB2450 maintenance therapy was safe and showed antitumor activity in patients with LS-SCLC.

Source:

Sun F. Safety and effectiveness of surgery or radiotherapy after PD-L1 Inhibitor (TQB-2450) and chemotherapy induction therapy in patients with limited-stage small cell lung cancer: a phase II trial. Abstract presented at: ESMO Annual Meeting, October 20-24, 2023; Madrid, Spain. Abstract 1991P.