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Nivolumab shrank tumours in roughly a fifth to a quarter of patients with three different advanced cancers, with responses that lasted more than a year and a hint that PD-L1 on the tumour predicted benefit.
This phase 1 dose-escalation and expansion study treated 296 patients with advanced melanoma, non-small-cell lung cancer, renal cell carcinoma, castration-resistant prostate cancer or colorectal cancer with the anti-PD-1 antibody BMS-936558 (nivolumab) at 0.1 to 10 mg/kg every two weeks. Objective responses occurred in 28% of melanoma, 18% of NSCLC and 27% of renal cancer patients, but none in prostate or colorectal cancer; of 31 responders followed for a year or more, 20 had responses lasting at least a year. Grade 3-4 drug-related adverse events occurred in 14%, and there were three deaths from pneumonitis. In 42 patients with tumour PD-L1 staining, 9 of 25 PD-L1-positive tumours responded versus none of 17 PD-L1-negative tumours. A companion paper (Brahmer et al.) reported similar activity for an anti-PD-L1 antibody.
This study is why PD-1 inhibitors were developed across cancers rather than in melanoma alone: unexpected activity in lung cancer, historically thought immune-resistant, changed drug development priorities industry-wide. It also introduced PD-L1 immunohistochemistry as a candidate biomarker and pneumonitis as a signature toxicity. Within five years PD-1 blockade was approved in more than ten cancers.
This is the most cited map of the immunotherapy revolution and a good first read before the trials. Its predictions largely held: PD-1 pathway antibodies became the most widely used cancer drugs, PD-L1 testing entered practice, and LAG-3 blockade was approved in melanoma a decade later.
This paper launched the immunotherapy era. It was the first randomised evidence that taking a brake off the immune system could extend life in a solid cancer, and it introduced clinicians to immune-related adverse events and to responses that arrive late or after apparent progression. Ipilimumab alone has since been superseded by PD-1 antibodies and combinations, but every checkpoint programme traces back to this result.
Shares Lieping Chen, Drew M. Pardoll, No one can predict who responds to immunotherapy, PD-1 / PD-L1 immune checkpoint & T-cell activation.
Shares Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable, Give immunotherapy in the morning, Randomised trials of stopping immunotherapy after one year versus continuing, Microbiome transplant as a routine immunotherapy adjunct.
Shares Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable, Give immunotherapy in the morning, Randomised trials of stopping immunotherapy after one year versus continuing, Microbiome transplant as a routine immunotherapy adjunct.
Shares Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable, Give immunotherapy in the morning, Randomised trials of stopping immunotherapy after one year versus continuing, Microbiome transplant as a routine immunotherapy adjunct.
Shares Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable, Randomised trials of stopping immunotherapy after one year versus continuing, Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch.
Shares Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable, Give immunotherapy in the morning, Randomised trials of stopping immunotherapy after one year versus continuing, Microbiome transplant as a routine immunotherapy adjunct.
Shares F. Stephen Hodi, Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma, Immune-related adverse events (irAEs), No one can predict who responds to immunotherapy.
Shares Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable, Give immunotherapy in the morning, Randomised trials of stopping immunotherapy after one year versus continuing, Microbiome transplant as a routine immunotherapy adjunct.