Oncology

TROP-2 ADCs provide meaningful benefit in pretreated advanced NSCLC but with notable ILD and high-grade toxicity

In seven studies including 1365 previously treated advanced NSCLC patients, TROP-2-directed ADCs achieved median OS 16.38 months and PFS 6.08 months. The pooled objective response rate was 29% and disease control rate 79%, exceeding typical outcomes with standard chemotherapy in this setting. EGFR-mutated tumors had significantly higher response likelihood than non-mutated disease (risk ratio 1.70, 95% CI 1.11-2.61). Grade ≥3 treatment-emergent adverse events occurred in 52% of patients, and interstitial lung disease in 9%, necessitating vigilant pulmonary monitoring. 1

Adding ICIs to standard NSCLC therapies improves survival broadly, with limited benefit in post-TKI EGFR-mutant disease

This systematic review of 36 RCTs (24,495 NSCLC patients) evaluated ICIs combined with standard systemic therapies versus monotherapy approaches. Across trials, adding ICIs to chemotherapy backbones significantly improved survival relative to either strategy alone. Benefits were generally consistent across histologic subtypes, PD-L1 expression levels, and disease stages, supporting wide use of chemo-IO combinations. EGFR-mutated NSCLC after progression on TKIs showed limited incremental benefit from ICI-containing combinations, highlighting a distinct therapeutic niche. 2

Baseline fatigue predicts severe, life-threatening, and fatal toxicities from systemic therapy across tumor types

This pooled SWOG cohort included 7086 patients from 17 phase 2 and 3 systemic-therapy trials across multiple cancers. At baseline, 39.1% reported at least some fatigue, which strongly correlated with subsequent high-grade adverse events. Compared with minimal fatigue, some-or-more fatigue doubled odds of severe toxicities (OR 2.09, 95% CI 1.58-2.78) and nearly doubled life-threatening or fatal events. Fatal toxic effects were also more likely (OR 2.35, 95% CI 1.07-5.19), with a dose–response for higher fatigue levels. 3