We recently published our analysis in the journal Cancer, explaining why we believe an trial testing pembrolizumab in this setting – KEYNOTE-A18 – should not change practice.
I found the following part of your article to be quite illuminating: “Sadly, in KEYNOTE-A18, when control-group patients recurred, access to pembrolizumab was not guaranteed. At the time of the reported analysis, only 51 of 193 (26%) patients that became incurable in the control group received immunotherapy as a post-protocol treatment (41 of 51 were treated with pembrolizumab). Also, no data regarding post-protocol treatment with chemotherapy and bevacizumab were made available. Thus, most patients in the control arm (treated with chemotherapy and radiation therapy) did not receive immunotherapy when their cancer relapsed or progressed, whereas by definition, every patient in the experimental arm initially received immunotherapy. The results are thus based on exposing everyone in the experimental arm to immunotherapy, as compared to only a quarter of patients in the control arm at the later stage.”
Only 25% in the control arm! These experiments have some issues unfortunately.
Regulators and HTA agencies should enforce stricter guidelines to ensure that control arm participants receive adequate post-protocol care.
This is a repeated pattern in industry-sponsored trials. Look at ADAURA and the adjuvant I/0 trials in esophageal and renal cell carcinomas
Thank you for doing this analysis
I found the following part of your article to be quite illuminating: “Sadly, in KEYNOTE-A18, when control-group patients recurred, access to pembrolizumab was not guaranteed. At the time of the reported analysis, only 51 of 193 (26%) patients that became incurable in the control group received immunotherapy as a post-protocol treatment (41 of 51 were treated with pembrolizumab). Also, no data regarding post-protocol treatment with chemotherapy and bevacizumab were made available. Thus, most patients in the control arm (treated with chemotherapy and radiation therapy) did not receive immunotherapy when their cancer relapsed or progressed, whereas by definition, every patient in the experimental arm initially received immunotherapy. The results are thus based on exposing everyone in the experimental arm to immunotherapy, as compared to only a quarter of patients in the control arm at the later stage.”
Only 25% in the control arm! These experiments have some issues unfortunately.