Long-term survival outcomes of consolidative local ablative therapy after response to first-line systemic treatment in oligometastatic NSCLC.

Abstract

8601 Background: The role of consolidative local ablative therapy (LAT) for patients (pts) with oligometastatic non-small cell lung cancer (NSCLC) who have responded to first line (1L) systemic treatment remains controversial especially after negative results from the NRG LU002 phase II/III trial. Data on long-term survival outcomes remain limited. Methods: We retrospectively collected data from EMR records of pts with oligometastatic NSCLC treated with 1L systemic treatment at the University of Pennsylvania Health System (2015–2025). Oligometastasis was defined as ≤4 distant metastases. Eligible pts had either genuine synchronous or induced oligometastatic disease and had achieved partial response (PR) or stable disease (SD) after 1L systemic treatment. We hypothesized that LAT would be associated with improved PFS and OS using time-dependent Cox regression analysis. Results: We identified 187 eligible pts. 53% were female; median age was 67 yrs and 31% had PD-L1 expression > 50%. At diagnosis, 90% had genuine oligometastatic disease: 45% with one metastatic lesion, 24% with two, 15% with three, and 11% with four lesions. Median follow- up time was 81 mos. (Reverse Kaplan-Meier). Of 187 pts, 21 received consolidative LAT in addition to maintenance therapy (LAT+) while 166 received maintenance therapy alone (LAT-). The LAT+ group was less likely to have bone metastasis (4.8% vs 34%, P = 0.007) and more likely to have adrenal metastasis (38% vs 19%, P = 0.049). In the LAT+ group, 67% had received chemo-immunotherapy as 1L and 19% had received immunotherapy alone, compared with 58% and 17% in the LAT− group, respectively (P = 0.80, Chi-square). In the LAT+ group, 76% achieved PR and 24% had SD to 1L therapy, compared with 65% and 35% in the LAT− group, respectively (P = 0.30, Chi-square). Median time from diagnosis to LAT delivery was 6 mos. (range, 2 – 24 mos.). The most common LAT modality was radiation (82%). The most common site of LAT was lung (68%). Median PFS was 28 vs 12 mos. and median OS was 98 vs 24 mos. in the LAT+ and LAT− groups, respectively. In time-dependent Cox models treating LAT as time-varying exposure, LAT+ was associated with improved PFS (P = 0.045) and OS (P = 0.003). A multivariable model confirmed the benefit of LAT after adjusting for PD-L1 status, treatment response, brain metastasis, bone metastasis, and nodal status (PFS: HR = 0.38, P = 0.004; OS: HR = 0.27, P = 0.002). Adverse events grade ≥3 were similar in both groups. Conclusions: LAT was associated with significantly improved PFS and OS in pts with oligometastatic NSCLC with an objective response or stable disease following 1L systemic treatment. Prospective studies are warranted to define pt characteristics that predict the greatest benefit from and optimal timing of LAT.