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Review
. 2020 Feb 19;9(2):565.
doi: 10.3390/jcm9020565.

New First Line Treatment Options of Clear Cell Renal Cell Cancer Patients with PD-1 or PD-L1 Immune-Checkpoint Inhibitor-Based Combination Therapies

Marc-Oliver Grimm  1 , Katharina Leucht  1 , Viktor Grünwald  2 , Susan Foller  1
Affiliations
Review

New First Line Treatment Options of Clear Cell Renal Cell Cancer Patients with PD-1 or PD-L1 Immune-Checkpoint Inhibitor-Based Combination Therapies

Marc-Oliver Grimm et al. J Clin Med. .

Abstract

In metastatic renal cell carcinoma (mRCC) the PD-1 immune-checkpoint inhibitor (ICI) Nivolumab became a standard second line treatment option in 2015 based on a significant improvement of overall survival compared to Everolimus. Current pivotal phase 3 studies showed that PD-1 ICI-based combinations were more efficacious than the VEGFR-TKI Sunitinib, a previous standard of care, leading to approval of three new regimens as guideline-recommended first-line treatment. Nivolumab plus Ipilimumab is characterized by a survival advantage, a high rate of complete response and durable remissions in intermediate and poor prognosis patients. Despite frequent immune-mediated side effects, fewer symptoms and a better quality of life were observed compared to Sunitinib. Pembrolizumab or Avelumab plus Axitinib were characterized by an improved progression-free-survival and a high response rate with a low rate of intrinsic resistance. In addition, Pembrolizumab plus Axitinib reached a significant survival benefit. The side effect profile is driven by the chronic toxicity of Axitinib, but there is additional risk of immune-mediated side effects of the PD-1/PD-L1 ICIs. The quality of life data published so far do not suggest any improvement regarding patient-reported outcomes compared to the previous standard Sunitinib. The PD-1/PD-L1 ICIs thus form the backbone of the first-line therapy of mRCC.

Keywords: avelumab; axitinib; immune checkpoint inhibitors; ipilimumab; nivolumab; pembrolizumab; renal cell carcinoma.

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Conflict of interest statement

M.-O G. reports grants from Novartis, BMS and Intuitive Surgical, outside the submitted work; consultant work for Novartis, BMS, Pfizer, Bayer Health Care, Astellas, Intuitive Surgical, AstraZeneca, MSD, Janssen Cilag, Ono Pharma, Ipsen Pharma and Merck Serono; and referee activities for Novartis, BMS, Pfizer, Astellas, Hexal, Apogepha, AstraZeneca, MSD, Ono Pharma, Ipsen Pharma, Medac and Merck Serono. K.L. declares no conflict of interest. V.G. reports grant from Bristol Myer Squibb, MSD, AstraZeneca, Pfizer and Novartis, outside the submitted work; consultant work for Pfizer, Novartis, Bristol Myer Squibb, Ipsen, Eisai, EUSAPharm, MSD, Merck Serono, Lilly and Roche; and personal fees from AstraZeneca, Pfizer, Novartis, Bristol Myer Squibb, MSD, Ipsen, Eisai, Lilly and Roche. He owns stocks from AstraZeneca, BMS and MSD. S.F. reports consultant work for Roche, MSD and Ipsen; referee activities for Roche, MSD, Bristol-Myers Squibb, Novartis and Pfizer; and personal fees from Ipsen. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results

Figures

Figure 1
Figure 1
Current therapeutic recommendations for clear cell renal cell cancer; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium. Zero of 6 risk factors (see text): favorable risk, 1–2 of 6 risk factors: intermediate risk, ≥3 of 6 risk factors: poor risk. (1) Anti-PD-1 antibody, (2) VEGFR-TKI, (3) anti-PD-L1 antibody, (4) anti-VEGF antibody, (5) anti-CTLA-4 antibody.
See this image and copyright information in PMC

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