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When we move cancer drugs from the second or third to the first line of treatment: what lessons can we learn from KEYNOTE-177 and JAVELIN-100
  1. Myung S Kim1,
  2. Vinay Prasad2,2
  1. 1 Department of Medicine, Division of Hematology and Oncology, Oregon Health & Science University, Portland, Oregon, USA
  2. 2 Department of Medicine, University of California San Francisco, San Francisco, California, USA
  1. Correspondence to Vinay Prasad, Department of Medicine, University of California San Francisco, San Francisco CA 94158, USA; vinayak.prasad{at}

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If the current standard of care is to give a new cancer drug as the second or third treatment option for a patient and there is interest in moving the drug to the front-line setting, how should we design and evaluate the study? Two recent examples can help us make sense of this question.

The recent KEYNOTE-177 Study1 evaluated pembrolizumab in microsatellite-instability-high (MSI-high) advanced colorectal cancer found that front-line use of pembrolizumab is associated with an improved progression-free survival (PFS), median 16.5 months versus 8.2 months, compared with standard chemotherapy. Similarly, JAVELIN-1002 found that among patients with metastatic urothelial cancer who achieved at least stable disease after four to six cycles of therapy, the use of maintenance avelumab increased median PFS from 2.0 months to 3.7 months and median overall survival (OS) from 14.3 months to 21.4 months. Both pembrolizumab and avelumab are checkpoint inhibitors that target immune checkpoints that unleash the immune response to cancer cells. These trials join studies such as KEYNOTE-483 and KEYNOTE-189,4 as justification to move a drug previously used in a latter line of therapy to the front-line setting. Moving these drugs to the front line will certainly increase the number of patients in each of these tumour types who receive the medication, growing market share and unfortunately, also, aggregate immune-related adverse events, but the key question is whether patients are better off as a result and how to make that assessment. Here, we discuss sequencing, duration and patient selection. …

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  • Contributors VP developed the concept of the paper and provided critical revision. MSK drafted the paper. Both authors approved the final paper and are accountable for all aspects of the work.

  • Funding VP was funded by Arnold Ventures.

  • Competing interests VP discloses: Research funding from Arnold Ventures, royalties from Johns Hopkins Press, Medscape and MedPage, consulting fees from UnitedHealthcare, speaking fees from eviCore and New Century Health and other (Plenary Session podcast has Patreon backers).

  • Provenance and peer review Not commissioned; externally peer reviewed.