“Although nivolumab (Opdivo) has demonstrated a clear survival advantage compared with chemotherapy in patients with progressive non–small cell lung cancer (NSCLC) who express PD-L1 in their tumor cells, the same cannot be said for those who are PD-L1–negative.
“As a result, researchers are seeking to elicit antitumor activity in a broader range of patients, notably through a multiarm trial evaluating the PD-1 inhibitor along with combinatorial approaches.
“CheckMate-227 (NCT02477826) is a phase III, open-label, randomized trial for patients with chemotherapy-naïve stage IV or recurrent NSCLC. The trial will enroll patients into separate groups according to PD-L1 expression status (≥1% or <1%).”
Last year, the U.S. Food and Drug Administration (FDA) approved two anti-PD-1 checkpoint inhibitors, a type of immunotherapy, for treatment of non-small cell lung cancer (NSCLC) in patients whose cancer has progressed after first-line treatment with chemotherapy. Now, the manufacturers of both drugs, pembrolizumab (made by Merck) and nivolumab (made by Bristol-Myers Squibb; BMS) are intent on expanding the indications for use of their drugs. To this end, they have conducted clinical trials testing each as a first-line treatment (i.e., in previously untreated patients), comparing them to standard chemotherapy. Continue reading…
“The addition of PD-1 antibody pembrolizumab to standard first-line chemotherapy for treatment-naïve advanced non-small-cell lung cancer significantly improves response rates and progression-free survival, researchers reported at the ESMO 2016 Congress in Copenhagen today.
“Pembrolizumab is a class of immunotherapeutic anti-cancer drugs called checkpoint inhibitors, which target the mechanism the tumour uses to shut down the body’s immune response.”
“Pembrolizumab is set to become a new option for first line treatment of patients with advanced lung cancer and high PD-L1 expression, according to the results of the phase III KEYNOTE-024 trial presented at the ESMO 2016 Congress in Copenhagen and published in the New England Journal of Medicine.
“‘Pembrolizumab is a PD-1 antibody approved for second line treatment of patients with advanced non-small-cell lung cancer (NSCLC) and PD-L1 expression in their tumour cells,’ said lead author Professor Martin Reck, chief oncology physician, Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. ‘KEYNOTE-024 is the first phase III trial of pembrolizumab as first line treatment in patients with high PD-L1 expression, who represent 27-30% of those with advanced NSCLC.’ ”
“Neoadjuvant immunotherapy with the PD-1 inhibitor nivolumab is safe and feasible prior to surgery for early lung cancer, researchers reported at the ESMO 2016 Congress in Copenhagen.
” ‘Until now nivolumab and the other anti-PD-1 and anti-PD-L1 drug studies have only been reported in metastatic or advanced lung cancer,’ said lead author Dr Patrick Forde, Assistant Professor of Oncology, Sidney Kimmel Comprehensive Cancer Centre, Johns Hopkins, Baltimore, US. “This was the first study of neoadjuvant PD-1 blockade in early stage lung cancer.”
“Pneumonitis occurs in approximately 5% of cancer patients treated with anti–programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy agents, according to a new analysis. The complication tends to be low grade and easily resolved, though it can worsen and result in death in rare cases.
“ ‘One of the remarkable characteristics of anti–PD-1/PD-L1 monoclonal antibodies is their relatively mild toxicity profile,’ wrote study authors led by Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center in New York. ‘However, immune-related adverse events can occur and may be severe.’ Pneumonitis is one such immune-related adverse event, and it accounted for several deaths in early trials of these agents.”
“PD-1 inhibitor–related pneumonitis occurred most frequently among patients with non–small cell lung cancer or renal cell carcinoma, according to results of a meta-analysis.
“The incidence of this adverse event also appeared greater during treatment with combination therapy.
“PD-1 inhibitors — including FDA–approved nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck) — are associated with unique toxicities known as immune-related adverse events. Pneumonitis is one such adverse event that, although rare, can be serious and life threatening.”
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