Luis Paz-Ares

This is the result that ended tumour mutational burden as a practical selector in lung cancer: in the regimen most patients receive, it selects nobody, and neither do the co-mutations most often quoted as reasons to withhold immunotherapy.

Patients with KRAS G12C lung cancer that has progressed after chemo-immunotherapy can take an oral KRAS inhibitor instead of docetaxel and gain a somewhat longer time to progression with fewer severe side effects, but should understand that most tumours become resistant within a year and that survival is not improved. KRAS G12C testing is worthwhile, but first-generation inhibitors are a step rather than a cure; combinations and next-generation inhibitors are the active research fronts.

Patients with small-cell lung cancer that has relapsed after chemotherapy now have a drug that works far better than topotecan or lurbinectedin, and it is the first T-cell engager approved for a solid tumour. Treatment requires inpatient monitoring for the first doses because of cytokine release syndrome, which most centres now manage on a short-stay basis. It does not yet apply to first-line treatment, where trials are ongoing.

Immunotherapy is now part of first-line treatment for extensive-stage small-cell lung cancer everywhere, on the strength of a gain measured in weeks. The size of that gain is the reason small-cell lung cancer remains the clearest unmet need in thoracic oncology.

ASCEND-4 gave ceritinib its 2017 US first-line approval and showed that a second-generation ALK inhibitor beats chemotherapy in untreated disease. In practice alectinib, brigatinib and lorlatinib, tested against crizotinib rather than chemotherapy, became the usual first-line choices, partly because ceritinib's gut side effects at 750 mg fasted were hard to live with.