Systemic and Oligo-Acquired Resistance to PD-(L)1 Blockade in Lung Cancer

Autor: Adam J. Schoenfeld, Hira A. Rizvi, Danish Memon, Narek Shaverdian, Matthew J. Bott, Jennifer L. Sauter, C. Jillian Tsai, Jayon Lihm, David Hoyos, Andrew J. Plodkowski, Rocio Perez-Johnston, Peter Sawan, Jacklynn V. Egger, Benjamin D. Greenbaum, Andreas Rimner, Gregory J. Riely, Charles M. Rudin, Valerie W. Rusch, Daniel R. Gomez, Matthew D. Hellmann
Rok vydání: 2022
Předmět:
Zdroj: Clinical Cancer Research. 28:3797-3803
ISSN: 1557-3265
1078-0432
Popis: Purpose: Clinical patterns and the associated optimal management of acquired resistance to PD-(L)1 blockade are poorly understood. Experimental Design: 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. Results: 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. Conclusions: 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.
Databáze: OpenAIRE
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