LBA60 - Stereotactic body radiation therapy with sequential immunochemotherapy as neoadjuvant therapy in resectable non-small cell lung cancer

Background

Phase 3 trials of neoadjuvant immunochemotherapy in patients with resectable non-small-cell lung cancer (NSCLC) have reported major pathological response (MPR) rates ranging from 30.2% to 48.5%. Stereotactic body radiotherapy (SBRT) may have an immunomodulating effect and augment the effect of preoperative immune checkpoint blockade monotherapy. In this single-arm phase 2 trial, we investigated the use of SBRT plus immunochemotherapy in the neoadjuvant setting for patients with resectable NSCLCs.

Methods

Eligiblepatients with resectable NSCLCs (stage II-IIIB as per the 8^th edition of the AJCC) without known EGFR/ALK alterations received SBRT (8Gy x 3 fractions) to the primary tumor followed by two cycles of PD-1 inhibitor tislelizumab plus platinum-doublet chemotherapy of each 21-day cycle. Patients without systemic disease progression proceeded to resection 4-6 weeks after treatment. The primary endpoint was MPR defined as 10% or fewer viable tumors in the primary tumor and lymph nodes. The sample size was determined based on Simon’s optimal two-stage design, considering a threshold MPR rate of 30% and an expected MPR rate of 50%. If there were 19 or more MPRs in 46 patients, the null hypothesis can be rejected.

Results

Between May 2022, and June 2023, 46 patients were enrolled, with 38 (82.6%) having stage III diseases. Two surgeries were canceled due to disease progression and G5 neutropenia, respectively. Forty-four (95.7%) patients underwent R0 resection and none of them required pneumonectomy. The study met the primary endpoint. The MPR rate was 76.1% (35/46, 95% CI: 61.2-87.4), and pathological complete response rate was 52.2% (24/46, 95% CI: 36.9-67.1). Nodal clearance (ypN0) was found in 35 of 46 cN1/2 cases (76.1%). Grade 3 or greater adverse events related to neoadjuvant treatment occurred in 12 patients (26.1%), the most frequent being neutropenia (13.0% [n=6]), pneumonia (4.3% [n=2]), and anemia (4.3% [n=2]). Two patients had delayed operations due to G3 pneumonia (77 and 134 days after the last cycle of immunochemotherapy). No deaths within 30 days of surgery were reported.

Conclusions

Neoadjuvant SBRT followed by immunochemotherapy is well tolerated, feasible, and yielded a high MPR rate.

Clinical trial identification

NCT05319574 Release date: April 8, 2022.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.