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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| Vydané v: | Clinical cancer research Ročník 28; číslo 17; s. 3797 |
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| Hlavní autori: | , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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United States
01.09.2022
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| ISSN: | 1557-3265, 1557-3265 |
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| Abstract | 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. |
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| AbstractList | 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. Clinical patterns and the associated optimal management of acquired resistance to PD-(L)1 blockade are poorly understood.PURPOSEClinical 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.EXPERIMENTAL DESIGNAll 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.RESULTSOf 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.CONCLUSIONSOligoAR 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. |
| Author | Shaverdian, Narek Bott, Matthew J Sauter, Jennifer L Rizvi, Hira A Hoyos, David Rudin, Charles M Rusch, Valerie W Egger, Jacklynn V Tsai, C Jillian Hellmann, Matthew D Lihm, Jayon Plodkowski, Andrew J Sawan, Peter Rimner, Andreas Gomez, Daniel R Schoenfeld, Adam J Perez-Johnston, Rocio Riely, Gregory J Memon, Danish Greenbaum, Benjamin D |
| Author_xml | – sequence: 1 givenname: Adam J orcidid: 0000-0002-2644-1416 surname: Schoenfeld fullname: Schoenfeld, Adam J organization: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York – sequence: 2 givenname: Hira A surname: Rizvi fullname: Rizvi, Hira A organization: Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 3 givenname: Danish surname: Memon fullname: Memon, Danish organization: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge – sequence: 4 givenname: Narek surname: Shaverdian fullname: Shaverdian, Narek organization: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 5 givenname: Matthew J surname: Bott fullname: Bott, Matthew J organization: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 6 givenname: Jennifer L orcidid: 0000-0001-6987-2294 surname: Sauter fullname: Sauter, Jennifer L organization: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 7 givenname: C Jillian surname: Tsai fullname: Tsai, C Jillian organization: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 8 givenname: Jayon orcidid: 0000-0002-1308-6507 surname: Lihm fullname: Lihm, Jayon organization: Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 9 givenname: David surname: Hoyos fullname: Hoyos, David organization: Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 10 givenname: Andrew J orcidid: 0000-0002-3772-370X surname: Plodkowski fullname: Plodkowski, Andrew J organization: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 11 givenname: Rocio orcidid: 0000-0001-9063-2615 surname: Perez-Johnston fullname: Perez-Johnston, Rocio organization: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 12 givenname: Peter surname: Sawan fullname: Sawan, Peter organization: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 13 givenname: Jacklynn V orcidid: 0000-0002-2180-4169 surname: Egger fullname: Egger, Jacklynn V organization: Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 14 givenname: Benjamin D surname: Greenbaum fullname: Greenbaum, Benjamin D organization: Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 15 givenname: Andreas surname: Rimner fullname: Rimner, Andreas organization: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 16 givenname: Gregory J surname: Riely fullname: Riely, Gregory J organization: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York – sequence: 17 givenname: Charles M orcidid: 0000-0001-5204-3465 surname: Rudin fullname: Rudin, Charles M organization: Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 18 givenname: Valerie W orcidid: 0000-0003-2345-6900 surname: Rusch fullname: Rusch, Valerie W organization: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 19 givenname: Daniel R surname: Gomez fullname: Gomez, Daniel R organization: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York – sequence: 20 givenname: Matthew D orcidid: 0000-0002-2670-9777 surname: Hellmann fullname: Hellmann, Matthew D organization: Oncology R&D, AstraZeneca, New York, New York |
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| Snippet | Clinical patterns and the associated optimal management of acquired resistance to PD-(L)1 blockade are poorly understood.
All cases of metastatic lung cancer... Clinical patterns and the associated optimal management of acquired resistance to PD-(L)1 blockade are poorly understood.PURPOSEClinical patterns and the... |
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| Title | Systemic and Oligo-Acquired Resistance to PD-(L)1 Blockade in Lung Cancer |
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