Pulmonary adverse events affected almost a third of lung cancer patients treated with ADCs in a 24-study meta-analysis

Pulmonary events in 30.9% of ADC-treated patients, grade 3 or higher in 6.9%

These pooled estimates come from 2,855 patients who received an ADC within randomised or prospective single-arm trials, and the confidence interval around the any-grade figure runs from 21.5% to 42.3%.

The width of that interval likely reflects, in part, variation in incidence between trials, which the random-effects model is designed to accommodate. Because single-arm trials have no comparator, the pooled figures describe how often pulmonary events occurred in treated patients. They are not rates in excess of a control arm.

Pneumonitis in 8.0%, and fatal pulmonary toxicity in 1.96%

Pneumonitis or ILD at grade 3 or higher was recorded in 2.8% of patients, and 6.2% stopped treatment because of pulmonary toxicity.

The authors identify pneumonitis and ILD as the key clinically actionable toxicity of this drug class in lung cancer. Pulmonary adverse event-related mortality of 1.96% means that roughly one patient in 50 treated with an ADC in these trials died of a pulmonary adverse event.

More pulmonary events in SCLC, more pneumonitis in NSCLC

Pulmonary adverse events of any grade were reported in 52.1% of patients with SCLC and 22.5% of those with NSCLC (p=0.005), whereas pneumonitis occurred in 12.1% of patients with NSCLC and 2.8% of those with SCLC (p<0.001).

The two comparisons point in opposite directions. A higher overall rate of pulmonary events in SCLC therefore did not translate into a higher rate of pneumonitis, which was the more frequent problem in NSCLC.

These are comparisons between trials, often testing different drugs in different populations. Tumour type in this analysis is therefore partly bound up with which ADCs were studied in which disease, and the difference cannot be attributed to tumour biology alone.

Risk associated with tumour subtype and with the drug itself

The authors conclude that pulmonary adverse events are common and clinically meaningful in patients with lung cancer treated with ADCs, and that the risk of pneumonitis or ILD is influenced by tumour subtype and by drug characteristics.

The literature search closed on 2 January 2025. ADCs are being tested in a growing number of lung cancer trials, so studies reported after that date are outside these estimates.