Early-onset hematological toxicity of docetaxel and survival in non-small cell lung cancer patients in the immune checkpoint inhibition era

PURPOSE Docetaxel remains a next-line treatment option for non-small cell lung cancer (NSCLC) following progression on immunotherapy. Early studies show docetaxel-associated hematological toxicity to be a predictive factor for improved survival outcomes, serving as a surrogate for the degree of systemic exposure and clinical activity. However, it is unclear whether docetaxel is still effective in the immunotherapy era. We investigated the relationship between first-cycle docetaxel-associated hematological toxicity and overall survival (OS) in patients treated during the immunotherapy era as a surrogate for clinical efficacy. METHODS We conducted a retrospective, multi-center cohort study across nine Dutch hospitals. Eligible patients with NSCLC received at least one cycle of docetaxel 75 mg/m² every 21 days between July 2017 and August 2024. Hematological toxicity outcomes were collected from electronic health records. The primary outcome was OS in patients with or without any grade of hematological toxicity in the first-cycle. RESULTS Data from 286 patients were available. The median OS was 7.2 months (95%-CI: 5.8–8.3). Any grade and grade III-IV hematological toxicities in the first cycle were observed in 30% (n=85) and 21% (n=61) of patients, respectively. Patients who experienced first-cycle grade III-IV docetaxel-associated hematological toxicity had a longer OS compared to no grade III-IV, with this effect becoming evident 12 months after the first docetaxel administration (HR=0.78, 95%-CI:0.57–1.07; Fleming-Harrington weighted log-rank test, p=0.0149). CONCLUSION Our findings indicate an association between improved OS later in time and first-cycle grade III-IV docetaxel-associated hematological toxicity in NSCLC post-immunotherapy, suggesting clinical activity of docetaxel in the immune checkpoint inhibition era.