The safety and efficacy of induction chemoimmunotherapy in initially unresectable stage III non-small cell lung cancer.

8058 Background: Definitive concurrent chemoradiation followed by consolidation immunotherapy is the standard of care for unresectable stage III non-small cell lung cancer. Several studies demonstrated addition of induction immunotherapy may further improve outcome, and it is necessary to assess the response-adapted strategy based on early tumor retraction to induction therapy. This study evaluated safety and treatment outcomes of induction chemoimmunotherapy followed by surgery or RT in unresectable stage III NSCLC. Methods: Patients with previously untreated, unresectable, pathologically and radiologically confirmed stage III NSCLC, EGFR/ALK-wild-type, with measurable disease were included. Patients received 3 to 4 cycles (Q3W) of chemoimmunotherapy including carboplatin (area under the curve [AUC] 5mg/mL/min), nab-paclitaxel (squamous NSCLC, 260mg/m 2 ) or pemetrexed (non-squamous NSCLC, 500mg/m 2 ), and tislelizumab(200mg). After Multi-Disciplinary Treatment, those operable patients after induction chemoimmunotherapy received radical minimally invasive surgery followed by 14 cycles of tislelizumab. The still unresectable patients received standard thoracic radiotherapy followed by 14 cycles of tislelizumab. Coprimary end points include 24-month progression-free survival (PFS) rate and incidence of grade 3 to 5 pneumonitis. Results: Between May 2020 and November 2023, a total of 59 patients received treatment (54 men [91.5%]; median [range] age, 65 [46-82] years; 34 patients [57.7%] with programmed cell death ligand 1 [PD-L1] tumor proportion score ≥ 1%); 40 patients [67.8%] were squamous cell NSCLC; 33.9%, 45.8%, and 20.3% patients were stage IIIA, IIIB and IIIC. Sixteen patients received radical minimally invasive surgery (9 pCR), 42 patients received thoracic radiotherapy, and 1 patient had brain metastasis after 2 cycles of induction therapy. The median follow-up period was 20.1 (1.9-44.1) months, and median PFS was not reached, the 24-months PFS rate was 77.6% (95%CI, 59.9%-88.2%). The objective response rate was 93.2% (95%CI, 83.5%-98.1%), and DCR was 98.3% (95%CI, 90.9%-100.0%). Grade 3 pneumonitis occurred in 2 of 59 patients (3.4%). Conclusions: The findings of this study indicate encouraging antitumor activity and manageable safety of induction chemoimmunotherapy, and the response-adapted strategy requires further exploration in locally advanced unresctable non-small cell lung cancer. Clinical trial information: ChiCTR2200064104. [Table: see text]