Characterization of outcomes in patients with metastatic non-small cell lung cancer treated with programmed cell death protein 1 inhibitors past RECIST v1.1-defined disease progression in clinical trials

Publication date: Available online 10 February 2017
Source:Seminars in Oncology
Author(s): Dickran Kazandjian, Patricia Keegan, Daniel L Suzman, Richard Pazdur, Gideon M Blumenthal
ImportanceBased 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). However, it remains unclear what the true benefit of TPP is.ObjectiveWe describe the findings of a pooled analysis of three clinical trials where treatment of patients with mNSCLC permitted TPP in terms of reduction in the sum of target lesions following initial RECIST-defined progression.DesignWe analyzed pooled data from three trials submitted to FDA evaluating anti-PD-1 therapy for the treatment of patients with mNSCLC in which patients were allowed to receive TPP. We identified patients who received TPP and the characteristics and post-TPP change in tumor burden. Results from this retrospective analysis are descriptively stated.ParticipantsAll patients had advanced or metastatic NSCLC and had previously received a platinum-based doublet regimen.ResultsIn 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.Conclusions and RelevanceOur evaluation indicated that 1.9% of anti-PD-1-treated patients with mNSCLC achieved a PR after receiving TPP. 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.



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