"Programmed Death 1 Blockade in Cancer Treatment". The New England Journal of Medicine. 2012. 366(26):2443-2454. PubMed•Full
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Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Criticisms 10 Funding 11 Further Reading
Does blockade of programmed death 1 (PD-1) enhance antitumor activity and is it associated with acceptable safety in patients with advanced melanoma, non–small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer?
Blockade of PD-1 with the antibody BMS-936558 generated objective responses in approximately one in four to one in five patients with non–small-cell lung cancer, melanoma, or renal-cell cancer. The safety profile was considered acceptable, making the antibody a viable option for cancer treatment. PD-L1 expression on tumors may be a predictive marker for response to anti–PD-1 therapy.
This study observed significant antitumor activity with the use of anti–PD-1 antibody in the treatment of multiple advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. Approximately 14% of patients experienced grade 3 or 4 drug-related adverse events, with only 5% discontinuing treatment due to these events. Three deaths from pulmonary toxicity were reported.
No guidelines were discussed in the article. This was an early phase clinical trial primarily assessing safety and preliminary efficacy.
Multicenter, phase 1 trial with open-label, dose-escalation, and cohort-expansion segments.
A total of 296 patients with advanced solid tumors were involved in the study, with diagnoses including melanoma, non–small-cell lung cancer, renal-cell cancer, castration-resistant prostate cancer, and colorectal cancer.
Inclusion Criteria Patients had documented advanced solid tumors, were aged 18 years or older, had measurable disease, and adequate organ function.
Exclusion Criteria Patients with a history of chronic autoimmune disease, prior treatment with T cell-modulating antibodies, conditions requiring immunosuppressive medication, or chronic infections were excluded.
Baseline Characteristics The majority of patients were heavily pretreated, with 47% having received at least three prior regimens.
Patients were given intravenous infusions of anti–PD-1 antibody (BMS-936558) every 2 weeks for each 8-week treatment cycle, up to a maximum of 12 cycles.
Primary Outcome Objective response rates (complete or partial response) were 18% in non–small-cell lung cancer, 28% in melanoma, and 27% in renal-cell cancer.
Safety and adverse event profiles, pharmacokinetics, and PD-L1 expression on tumor cells as a biomarker for response to therapy.
The study was open-label and did not have a comparator arm. The predictive value of PD-L1 expression for treatment response needs further exploration, and selection bias may influence the results due to optional biopsies performed on a non-random subset of patients.
The study was funded by Bristol-Myers Squibb and other sources.
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