Acquired resistance to PD-(L)1 blockade is frequent in non-small cell lung cancer (NSCLC), occurring in a majority of initial responders. Patients with acquired resistance may have unique properties of persistent anti-tumor immunity that could be re-harnessed by investigational immunotherapies. The absence of a consistent clinical definition of acquired resistance to PD-(L)1 blockade and lack of uniform criteria for ensuing enrollment in clinical trials remains a major barrier to progress; such clinical definitions have advanced biologic and therapeutic discovery. We examine the considerations and potential controversies in developing a patient-level definition of acquired resistance in NSCLC treated with PD-(L)1 blockade. Taking into account the specifics of NSCLC biology and corresponding treatment strategies, we propose a practical, clinical definition of acquired resistance to PD-(L)1 blockade for use in clinical reports and prospective clinical trials. Patients should meet the following criteria: received treatment that includes PD-(L)1 blockade; experienced objective response on PD-(L)1 blockade (inclusion of a subset of stable disease will require future investigation); have progressive disease occurring within 6 months of last anti-PD-(L)1 antibody treatment or rechallenge with anti-PD-(L)1 antibody in patients not exposed to anti-PD-(L)1 in 6 months.
- Schoenfeld, A. J.
- Antonia, S. J.
- Awad, M. M.
- Felip, E.
- Gainor, J.
- Gettinger, S. N.
- Hodi, F. S.
- Johnson, M. L.
- Leighl, N. B.
- Lovly, C. M.
- Mok, T.
- Perol, M.
- Reck, M.
- Solomon, B.
- Soria, J. C.
- Tan, D. S. W.
- Peters, S.
- Hellmann, M. D.
Keywords
- PD-(L)1 blockade
- acquired resistance
- checkpoint inhibitor
- immunotherapy
- lung cancer
