505P - Neoadjuvant PD-1 inhibitor (tislelizumab) plus platinum–etoposide in patients with limited-stage small cell lung cancer: A phase II trial

Background

The RATIONALE-312 study reports PD-1 inhibitor (tislelizumab) plus platinum–etoposide could improve survival of patients with extensive-stage small-cell lung cancer (SCLC). Based on this, we initiated a pilot study to explore the safety and feasibility of neoadjuvant Tislelizumab plus platinum–etoposide in limited-stage SCLC.

Methods

Treatment-naïve limited-stage SCLC patients with ECOG PS 0-1 status were enrolled. Patients received 4 cycles of Tislelizumab (200mg, q3w) plus platinum (Cisplatin 75 mg/m² or Carboplatin AUC5) – etoposide (100 mg/m²). The feasibility of surgery was then reassessed by radiology. Candidates for complete resection underwent surgery; otherwise, they received radiotherapy. Patients who received surgery also received adjuvant Tislelizumab plus platinum–etoposide therapy for 4 cycles. Primary endpoints were safety and feasibility. Secondary endpoints were objective response rate (ORR), pathologic response, and survival.

Results

A total of 8 eligible patients were enrolled up to April 2023. The median age was 65 (range: 57-70) with 6 male patients and 7 smokers. Among them, 1, 4, and 3 patients had stage ⅡB, ⅢA and ⅢB disease, respectively. No previously unreported toxic effects were observed. Treatment-related adverse events (TRAEs) of any grade occurred in 7 of 8 (87.5%) patients. Grade 3-4 events occurred in 6 of 8 (75%) patients. There were no severe adverse events. The majority of TRAEs was chemotherapy-related, and 2 patients suffered mild immune-related thyroid dysfunction. Seven patients completed 4 cycles of neoadjuvant therapy, and the best ORR was 85.7% (5 partial response and 1 stable disease). Of the 7 patients, 5 were assessed to be resectable. There were no treatment-related surgical delays. R0 resection and pathological downstaging were achieved for all 5 patients (100%) without any serious surgical complications. At a median of 18 months (range: 10 - 20) of follow-up, all patients were alive, and all the patients who received surgery were recurrence-free.

Conclusions

Neoadjuvant Tislelizumab plus platinum–etoposide was associated with tolerable side effects and was effective for patients with limited-stage SCLC.

Clinical trial identification

NCT04542369.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Pulmonary Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.