Ablation plus immunotherapy versus immunotherapy alone in patients of advanced NSCLC who develop oligo-residual disease after anti-PD-1/L1 therapy (BOOSTER): a randomized phase 2 trial

Local consolidative therapy (LCT) has been demonstrated to enhance the survival benefits of immunotherapy in non-small cell lung cancer (NSCLC) patients with oligometastatic or oligoprogressive disease. This randomized, phase 2 trial investigated the efficacy and safety of ablation combining continuous immunotherapy in NSCLC patients with oligo-residual disease (ORD) after anti-PD-1/L1 therapy (ChiCTR, identifier: ChiCTR2000032479). From March 2021 to March 2024, 65 patients were randomly assigned (2:1) to ablation combination group (n = 43) and immunotherapy maintenance group (n = 22), and the full analysis set finally included 42 patients in ablation plus immunotherapy group and 20 patients in immunotherapy maintenance group. With a median follow-up duration of 17.8 months, patients receiving ablation combination were associated with significantly longer PFS (median 26.7 vs. 11.7 months, p < 0.001, HR = 0.213, 95%CI 0.099-0.461) and a trend of longer OS (p = 0.036, HR = 0.242, 95%CI 0.057-1.019) than those without ablation. Subgroup analysis showed that cryoablation (n = 13) yielded potentially superior survival than thermal ablation (n = 31) (mPFS: NA vs. 22.4 months, p = 0.011), which might induced by the elevated level of IFN-α after cryotherapy compared to thermal ablation (p = 0.078). Additionally, ablation combination group showed a decreased rate of systemic progression pattern compared with immunotherapy maintenance group. Regarding safety, the combination of ablation and immunotherapy was well tolerated, with only 1 patient experiencing grade 3 pneumothorax after ablation. In conclusion, the addition of ablation is well-tolerated and prolongs the survival of immunotherapy in patients with advanced NSCLC who develop ORD after anti-PD-1/L1 therapy, while cryoablation showing potentially superior survival benefit compared to thermal ablation.