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

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, followe...

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Vydáno v:Clinical cancer research Ročník 28; číslo 17; s. 3797
Hlavní autoři: Schoenfeld, Adam J, Rizvi, Hira A, Memon, Danish, Shaverdian, Narek, Bott, Matthew J, Sauter, Jennifer L, Tsai, C Jillian, Lihm, Jayon, Hoyos, David, Plodkowski, Andrew J, Perez-Johnston, Rocio, Sawan, Peter, Egger, Jacklynn V, Greenbaum, Benjamin D, Rimner, Andreas, Riely, Gregory J, Rudin, Charles M, Rusch, Valerie W, Gomez, Daniel R, Hellmann, Matthew D
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.09.2022
Témata:
B7-H1 Antigen
Biomarkers, Tumor - therapeutic use
Carcinoma, Non-Small-Cell Lung - drug therapy
Humans
Immunotherapy
Lung Neoplasms - pathology
Tumor Burden
ISSN:1557-3265, 1557-3265
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1557-3265
1557-3265
DOI:10.1158/1078-0432.CCR-22-0657