Tumour mutational burden decides who gets immunotherapy in some settings, but every sequencing panel calculates it differently. A shared calibration would make the number mean the same thing everywhere.
The Friends of Cancer Research TMB Harmonization Project showed that panel-derived TMB values can be aligned to whole-exome TMB with panel-specific calibration and reference samples. Yet the pembrolizumab approval for TMB above 10 mutations per megabase was tied to a single assay. Requiring each panel to report a calibrated TMB traceable to a common reference set, with published calibration curves, would make the biomarker portable across assays.
Patients whose kidney cancer has been removed but who are at high risk of recurrence (large or high-grade tumours, node involvement, or resected metastases) can now be offered a year of pembrolizumab, which increases the chance of being alive and cancer-free several years later. Roughly nine patients need treatment to prevent one recurrence at two years, and some will have permanent side effects, so shared decision-making matters. Why pembrolizumab succeeded where similar drugs failed is not fully understood.
Most patients with newly diagnosed advanced non-squamous lung cancer that lacks a targetable mutation should receive chemotherapy plus pembrolizumab; those with PD-L1 of 50% or more may reasonably receive pembrolizumab alone. About one in five patients is alive at five years, compared with roughly one in ten with chemotherapy alone. Patients with EGFR or ALK alterations were excluded and should have targeted therapy first.
Shares Foundation Medicine (Roche), Tempus AI, Next-generation sequencing (NGS), Biomarkers are not validated or standardised.
Shares KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery, KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation, Pembrolizumab.
Shares KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery, KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation, Pembrolizumab.
Shares Tumour mutational burden (TMB), Whole-exome & whole-genome sequencing, Biomarkers are not validated or standardised.
Shares KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation, No one can predict who responds to immunotherapy, Pembrolizumab.
Shares Foundation Medicine (Roche), Tempus AI.
Shares Foundation Medicine (Roche), Tempus AI, Next-generation sequencing (NGS).
Shares Foundation Medicine (Roche), Tempus AI.