医学
封锁
内科学
肿瘤进展
癌症
肿瘤科
肺癌
无进展生存期
进行性疾病
后天抵抗
放射治疗
胃肠病学
外科
疾病
化疗
受体
作者
Adam J. Schoenfeld,Hira Rizvi,Danish Memon,Narek Shaverdian,Matthew Bott,Jennifer L. Sauter,C. Jillian Tsai,Jayon Lihm,David Hoyos,Andrew J. Plodkowski,Rocío Pérez-Johnston,Peter Sawan,Jacklynn V. Egger,Benjamin Greenbaum,Andreas Rimner,Gregory J. Riely,Charles M. Rudin,Valerie W. Rusch,Daniel R. Gomez,Matthew D. Hellmann
标识
DOI:10.1158/1078-0432.ccr-22-0657
摘要
Clinical patterns and the associated optimal management of acquired resistance to PD-(L)1 blockade are poorly understood.All cases of metastatic lung cancer treated with PD-(L)1 blockade at Memorial Sloan Kettering were reviewed. In acquired resistance (complete/partial response per RECIST, followed by progression), clinical patterns were distinguished as oligo (OligoAR ≤ 3 lesions of disease progression) or systemic (sAR). We analyzed the relationships between patient characteristics, burden/location of disease, outcomes, and efficacy of therapeutic interventions.Of 1,536 patients, 312 (20%) had an initial response and 143 developed AR (9% overall, 46% of responders). OligoAR was the most common pattern (80/143, 56%). Baseline tumor mutational burden, depth of response, and duration of response were significantly increased in oligoAR compared with sAR (P < 0.001, P = 0.03, P = 0.04, respectively), whereas baseline PD-L1 and tumor burden were similar. Post-progression, oligoAR was associated with improved overall survival (median 28 months vs. 10 months, P < 0.001) compared with sAR. Within oligoAR, post-progression survival was greater among patients treated with locally-directed therapy (e.g., radiation, surgery; HR, 0.41; P = 0.039). Fifty-eight percent of patients with oligoAR treated with locally-directed therapy alone are progression-free at last follow-up (median 16 months), including 13 patients who are progression-free more than 2 years after local therapy.OligoAR is a common and distinct pattern of acquired resistance to PD-(L)1 blockade compared with sAR. OligoAR is associated with improved post-progression survival and some cases can be effectively managed with local therapies with durable benefit.