A phase II, two-cohort study of neoadjuvant chemotherapy plus tislelizumab ± bevacizumab followed by hypofractionated radiotherapy, concurrent chemotherapy, and consolidative immunotherapy in locally advanced non-small cell lung cancer (GASTO-1086).
Authors: Wang DaQuan , Qiu Bo , Liu FangJie , Mo Yiwen , He Wen-zhuo , Guo JinYu , Zou YingYi , Hu Ying-Ying , Xia Liang-Ping , Liu QianWen , Liu Hui 
Published: June 2024

8065

Background: Neoadjuvant chemoimmunotherapy holds promise for enhancing clinical outcomes in patients with resectable non-small cell lung cancer (NSCLC). The assessment of Ki values, derived from dynamic total-body PET/CT scans, has emerged as a crucial determinant of treatment response to neoadjuvant chemoimmunotherapy. This study investigated the efficacy of neoadjuvant chemoimmunotherapy ± bevacizumab, guided by the Ki value, followed by hypofractionated radiotherapy, concurrent chemotherapy (hypo-CCRT), and consolidative immunotherapy in unresectalbe stage III NSCLC. Methods: Conducted as a phase II, two-cohort trial in patients with unresectable stage III NSCLC, the study involved dynamic total-body [18F]FDG PET/CT scans to derive Ki values from primary tumors. Cohort A, comprising High FDG Ki patients (Ki > 2.779 ml/min/100g), received neoadjuvant therapy with nab-paclitaxel, cisplatin, and tislelizumab 200mg every 3 weeks for 2 cycles. Meanwhile, Cohort B, consisting of Low FDG Ki patients (Ki ≤ 2.779 ml/min/100g), received nab-paclitaxel, cisplatin, tislelizumab 200mg, and bevacizumab 7.5mg/kg every 3 weeks for 2 cycles. Subsequently, hypo-CCRT was administered, and patients without disease progression and grade (G) 2+ pneumonitis received consolidative tislelizumab 200mg every 3 weeks for up to 12 months. Objective response rate (ORR) and toxicities were analyzed, with the trial registered under ClinicalTrials.gov, NCT05468242. Results: Enrollment occurred between July 21, 2022, and Nov 10th, 2023, with 29 patients in cohort A and 26 in cohort B. Cohort B exhibited a higher proportion of stage IIIC patients compared to cohort A (57.7% vs. 20.7%, P = 0.019). Post-neoadjuvant therapy, ORRs were 89.7% (26/29) in cohort A and 92.3% (24/26) in cohort B. Following hypo-CCRT, ORRs increased to 96.6% (28/29) in cohort A and 92.3% (24/26) in cohort B. During neoadjuvant therapy, G3 leukopenia occurred in 3.4% (1/29) of cohort A, with no G3+ toxicities in cohort B. In the hypo-CCRT phase, G3 neutropenia and G2 pneumonitis were observed in both cohorts (G3 neutropenia: 3.4% in cohort A vs. 3.8% in cohort B; G2 pneumonitis: 6.9% in cohort A vs. 7.7% in cohort B), with no Grade 3+ adverse events during the consolidative tislelizumab phase. Conclusions: The Ki value derived from dynamic total-body FDG PET/CT proved instrumental in guiding the addition of bevacizumab to neoadjuvant therapy. Both cohorts exhibited promising responses to neoadjuvant therapy, suggesting that neoadjuvant chemotherapy plus tislelizumab ± bevacizumab, followed by hypo-CCRT and consolidative tislelizumab, is effective and well-tolerated for unresectable, stage III NSCLC patients. Longer follow-up is essential to validate these findings. Clinical trial information: NCT05468242 .