P3.02c-033 Patterns of Progression and Management of Acquired Resistance to Anti-PD-1 Antibodies in Advanced Non-Small Cell Lung Cancer: Topic: IT

Abstract

Anti-PD-1 antibodies (pembrolizumab and nivolumab) have shown improved overall survival in second-line treatment for metastatic non-small cell lung cancer (NSCLC) with durable responses. We aimed to assess the pattern of disease progression amongst patients who initially responded to anti-PD-1 agents and their subsequent management. We retrospectively assessed all patients who commenced single-agent anti-PD-1 antibodies between June 2012 and February 2016 at a single centre. Radiological responses were assessed by the investigator using RECIST 1.1 and irRC. Progressive disease (PD) patterns were defined as solitary, oligometastatic (2-3 lesions), generalized (>3 lesions), enlargement of existing or new lesions, visceral or non-visceral. Management and survival after progression were examined. A total of 81 patients received single-agent pembrolizumab (n=43) or nivolumab (n=38). Of the seventeen (21.3%) patients achieving partial response, three were treatment-naïve, fifteen (88.2%) were former or current smokers, none had EGFR mutation or ALK translocation. The median number of disease sites at baseline was three, and two patients had stable brain metastases after radiotherapy at the commencement of anti-PD1 treatment. Ten (58.8%) responders developed acquired resistance, with a median time to progression of 20.2 months. Nine (90%) had solitary (n=4) or oligometastatic (n=5) progression. Five (50%) progressed only at existing sites, three (30%) developed new lesions only, and two (20%) progressed at both existing and new sites. Four (40%) progressed at non-visceral sites only, and one progressed in the brain at a previously treated site. Five (50%) patients underwent local treatment to solitary (n=2) or oligoprogressive disease (n=3) with all five achieving local control with radiotherapy. Seven(70%) continued anti-PD-1 agents beyond progression, while the three (30%) remaining patients did not receive any further therapy. With a median follow-up of 24.8 months, five (50%) of the patients had died, one from an infective exacerbation of COPD, one from type 1 respiratory failure, and three from disease progression. The median duration of treatment was 4.35 months (1.96 to 11.46) and the median overall survival after progression was 11.44 months. This study suggested that acquired resistance to anti-PD1 agents could often result in solitary or oligometastatic progression, and that CNS progression was uncommon. In a subset of patients, treatment beyond progression with or without local therapy to oligometastatic disease may provide ongoing and durable clinical benefit.