The edition · Pulmonology
TP53 status doubles the case for adding chemotherapy to osimertinib
A 294-patient phase 3 trial in EGFR-mutant lung cancer with concurrent TP53 mutation reports progression-free survival of 34.0 against 15.6 months; a COPD composite endpoint predicts later exacerbations and death; and awake ECMO fails in four of ten selected patients.
The edition in brief
The pulmonology desk opens with a randomised phase 3 trial at 17 Chinese sites in 294 patients with treatment-naive advanced non-squamous non-small-cell lung cancer carrying both an EGFR-sensitising mutation and a TP53 mutation. Adding pemetrexed and carboplatin to osimertinib extended median progression-free survival from 15.6 to 34.0 months (hazard ratio 0.44, 95% CI 0.32-0.60), with overall survival data only 30.6% mature and more grade 3 or higher adverse events in the combination arm. A post hoc analysis across five phase 3 COPD trials defines disease stability as no moderate or severe exacerbation and no worsening in COPD Assessment Test score or FEV1, achieved by 22% on triple therapy in IMPACT; patients stable at week 28 had a 45.7% lower subsequent exacerbation risk and a 51.7% lower risk of all-cause mortality. An international retrospective cohort of 307 patients given extracorporeal membrane oxygenation without invasive ventilation for acute respiratory distress syndrome reports 90-day mortality of 30.1% in primary awake ECMO and 14.9% in extubated ECMO, with strategy failure in 40.7% and 24.2% respectively. A post hoc analysis of two bronchiectasis trials suggests baseline symptom burden separates who responds to an anti-inflammatory from who responds to an inhaled antibiotic. A pearl covers inhaler technique. The edition closes with US screening uptake data showing former smokers who quit over 15 years ago are screened at less than half the rate of currently eligible adults.
In EGFR-mutant lung cancer, TP53 co-mutation identifies who needs chemotherapy too
Test for TP53 alongside EGFR at diagnosis, and offer chemotherapy with osimertinib when both are present.
COPD 'stability' at 28 weeks predicts what happens over the next year
Ask at each COPD review whether the patient meets all three stability criteria, and act when they do not.
ECMO without a tube: the failures cluster in the first ten days
If you attempt awake ECMO, set the intubation trigger before you start and expect to use it in four of ten patients.
In bronchiectasis, how symptomatic the patient is may pick the drug
Start recording a bronchiectasis symptom score at baseline — the treatment choice may come to depend on it.
Watch the inhaler before you change the inhaler
Before stepping up therapy for poor control, watch the patient use their own inhaler.
The former smoker who quit twenty years ago is the one being missed
Identify the patients with a heavy smoking history who quit more than fifteen years ago — no system is flagging them, and they do not think they are at risk.
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