Long-term follow-up of “adjuvant” pembrolizumab following locally ablative therapy for oligometastatic non-small cell lung cancer.
Authors: Cantor David John , Davis Christiana , Ciunci Christine Agnes , Aggarwal Charu , Evans Tracey L. , Alley Evan W. , Cohen Roger B. , Bauml Joshua Michael , Langer Corey J. 
Published: June 2023

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Background: Patients with oligometastatic (OM) non-small cell lung cancer (NSCLC) benefit from local ablative therapies (LAT); however, the role of adjuvant systemic therapies post LAT remains less clear. In a single-arm Phase II clinical trial (NCT02316002), we demonstrated that patients with OM NSCLC treated with adjuvant pembrolizumab following LAT had superior progression free survival (PFS) compared to historical controls. Here, we present long term follow-up on PFS and overall survival (OS). Methods: Patients with OM (≤ 4 metastatic sites) NSCLC treated with LAT to all sites received pembrolizumab every 21 days for up to 16 cycles from February 1, 2015 through September 30, 2017. Other key inclusion criteria included ECOG PS 0-1 and the absence of autoimmune diseases. Patients were eligible regardless of the number of prior therapies or PD-L1 status. Our study design was an intention to treat analysis with a null hypothesis that PFS would be equivalent to historical controls (6.6 months) compared with the alternative that PFS would be greater than 10 months. Assuming 42 patients enrolled over 2 years, we calculated 80% power to detect improvement in PFS with a 1-sided 5% significance level. Primary efficacy endpoint was PFS from the start of pembrolizumab and was defined as evidence of progressive disease (PD) via RESCIST v1.1 criteria, death, or last contact. Secondary endpoints included OS, determined by date of death or last contact, and safety. Cox proportional hazard models were performed to assess associations between clinicopathologic features and PFS or OS. Results: 51 patients enrolled in the study; 45 patients (median age, 64 years [range, 46-82]; 21 [47%] women; 31 [69%] with solitary OM site) received pembrolizumab following LAT. Patients received a median of 11 cycles of pembrolizumab; 18 (40%) patients completed 16 cycles. At the data cutoff (December 1, 2022; median f/u, 65.8 months), 32 patients had PD, 19 patients died, and 13 patients had no evidence of relapse. Median PFS was 19.7 months (95% CI, 7.6-31.7 months); median OS was not reached (95% CI, NR-NR). OS rate at 5 years was 60.0% (SE, 7.4%). Upon PD, 94% of patients received salvage therapies. Median OS from the time of PD was 39.7 months (95% CI, 13.8-65.6 months). Metachronous OM disease was significantly associated with improved OS (HR, 3.2 [95% CI, 1.5-6.7] and PFS (HR, 2.9 [95% CI, 1.2-7.5]) via multivariate Cox proportional-hazard models. The number of OM sites, CNS disease, nodal stage at diagnosis, or tumor PD-L1 status was not significantly associated with PFS or OS. We did not observe new safety signals for pembrolizumab following LAT aside from those previously reported. Conclusions: Pembrolizumab following LAT for OM NSCLC results in promising PFS and OS compared to historical experience with a tolerable safety profile. Further investigation of this approach with a randomized trial is warranted. Clinical trial information: NCT02316002 .