title: Characterization of outcomes in patients with metastatic non-small cell lung cancer treated with programmed cell death protein 1 inhibitors past RECIST version 1.1-defined disease progression in clinical trials.
abstract: Based on anecdotal cases of clinically important decreases in tumor size following initial evidence of disease progression when treating patients with anti-PD-1 therapies, investigators have conducted clinical trials in patients with metastatic non-small lung cancer (mNSCLC) receiving anti-PD-1 therapy allowing for treatment past RECIST-defined disease progression (TPP). We describe the findings of a pooled analysis of three clinical trials submitted to the US Food and Drug administration (FDA) where treatment of patients with mNSCLC permitted TPP in terms of reduction in the sum of target lesions following initial RECIST-defined progression. We identified patients who received TPP and the characteristics and post-TPP change in tumor burden. All patients had advanced or mNSCLC and had previously received a platinum-based doublet regimen. In total, 535 patients were treated with anti-PD-1 therapy in three clinical trials of which 121 patients (23%) received TPP. Among all 535 patients treated with anti-PD-1 therapy, the partial response (PR) rate (≥30% reduction in the size of target lesions compared to baseline) following TPP was 1.9% (10 of 535) or 8.3% (10 of 121) in the TPP subgroup. Patients who responded to TPP were more likely to have responded to the initial course of anti-PD-1 therapy, prior to progression. The subgroup of patients who received TPP appeared to have similar baseline characteristics and response to initial treatment compared to the overall population. This suggests that a treatment strategy that includes TPP may not benefit the overall population. The risks of TPP should be weighed against the low likelihood of a PR and the potential for changing to a different therapy with a higher likelihood of benefit.
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD; Myeloma program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. Electronic address: Dickran.kazandjian@fda.hhs.gov.
authors.forename: Dickran
authors.initials: D
authors.lastname: Kazandjian
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Suzman
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Blumenthal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D066066:Response Evaluation Criteria in Solid Tumors
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Immunotherapy; Non-small cell lung carcinoma; PD-1 inhibitor; Treatment beyond progression