The immun-oncology innovations of cancer treatment, the PD-1 inhibitor pembro and nivo were registered by EMA for the treatment of metastatic melanoma. The monoclonal, humanized, IgG4k antibody pembro and the human IgG4 nivo block the PD-L1 and/or PD-L2 interactions and enhance the antitumor immune response of T cells. The current outcome measures do not assess the long term benefit of I-O therapies. In the Keynote-002 ipi refracter group, the pembro 2mg/kg arm CR was 2%, PR 19%, and SD 18%. In the 10 mg/kg pembro arm CR was 3%, PR 23%, SD 18%. In the chemotherapy group, ICC, there was no CR, while PR occurred in 4%, SD in 18%.
To evaluate the efficacy of pembro and nivo, to measure their relative clinical value by calculating NNT, the number of patients who need to be treated to prevent one death. We analyzed the survival data and calculated the NNT values of the PhII Keynote-002 study pembro vs ICC in ipi-refracter group, the PhIII Keynote-006 study pembro vs ipi group, the PhIII CheckMate-066 study nivo vs DTIC group data.
In the Keynote-002, the 2mg/kg pembro arm NNT:3,8, the NNT value of the 10mg/kg group: 4,5.In the Keynote-006 pembro vs ipi study, the 1Y OS rate was 71,4% in the 10mgQ2W group, 68,4% in the 10mgQ3W group, and 58,2% in the ipi group.The NNT of the 10mgQ2W patient group: 4,67, the NNT of the 10mg/Q3W was 6,66. In the CheckMate-066 study the nivo group 1YOS% 70,7, the estimated 2Y OS% was 57,7% and the DTIC group 1YOS% was 46,3% and 2Y 26,7%. The NNT value of nivo group was 4,16-9,17.
Based on PhII-III studies, the NNT values of novel immunotherapies demonstrate the exceptional relative clinical value of PD-1 inhibitors. The prevention of one death, their clinical value is based on their NNT values, pembro: 3,8-6,66, nivo 4,16-9,17. These results show the future potential of I-O clinical benefit. Over the follow up time the risk reduction is not constant it is recommended to calculate the NNT values at least twice, not only at one specific time point, if necessary data are available from the trials.
Clinical trial identification
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All authors have declared no conflicts of interest.