Efficacy of nintedanib plus docetaxel in patients with refractory advanced epidermal growth factor receptor mutant lung adenocarcinoma

Mariona Riudavets, Joaquim Bosch-Barrera, Luís Cabezón-Gutiérrez, Pilar Diz Taín, Ainhoa Hernández, Miriam Alonso, Remei Blanco, Elisa Gálvez, Amelia Insa, Xabier Mielgo, Teresa Morán, Santiago Ponce, Diana Roa, José Miguel Sánchez, Margarita Majem

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

5 Citations (Scopus)

Résumé

Background: Anti-angiogenic agents are reported to exert clinical activity in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). We evaluated the outcomes of the combination of docetaxel plus nintedanib in refractory NSCLC patients harboring EGFR mutations. Methods: We retrospectively analyzed 19 patients with advanced EGFR-mutant NSCLC who had progressed to EGFR tyrosine kinase inhibitors (TKI) and platinum-based chemotherapy receiving docetaxel and nintedanib at 14 Spanish institutions from January 2013 to December 2019. Kaplan–Meier and log-rank tests were used to evaluate progression-free survival (PFS) and overall survival (OS). Results: Median age was 58.9 years (range 42.8–81), 73.7% were female. All patients were Caucasian, and 73.7% were never or light smokers. The baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0–1 in 94.7% of patients. All patients had adenocarcinoma. Brain and liver metastases were present in 47.4% and 31.6% of patients, respectively. The most common EGFR mutations were exon 19 deletion (52.6%) and exon 21 L858R mutation (36.8%); 47.4% patients presented the EGFR T790M. 94.8% of the patients had received 2–3 previous treatment lines. Docetaxel was administered at 75 mg/m2/3 weeks to 16 patients, at 60 mg/m2 to 2 patients and at 45 mg/m2 to one patient. Nintedanib was given until disease progression or unacceptable toxicity at 200 mg twice daily except in 2 patients who received 150 mg twice daily and one patient who received 100 mg/12 h. With a median follow-up of 11.4 months (1–38), the median PFS was 6.1 months [95% confidence interval (CI), 4.9–7.3] and the median OS 10.1 months (95% CI 5.9–14.3). The objective response rate (ORR) was 44.4% (23.7–66.8%) and the disease control rate (DCR) 72.2% (49.4–88.5%). Efficacy tended to be greater in patients with the acquired T790M who had received osimertinib, with a median PFS of 6.3 (95% CI 2.1–10.5) versus (vs.) 4.8 (95% CI 3.5–6.1) and a median OS of 12.3 months (95% CI 8.6–16.0) vs. 6.7 months (95% CI 3.9–9.4), although this tendency was not statistically significant (p = 0.468 and p = 0.159, respectively). Sixteen patients (84.2%) had a total of 34 adverse events (AEs), with a median of two (0–6) AEs per patient. The most frequent AEs were asthenia (20.6%) and diarrhea (20.6%). One treatment-related death due to portal thrombosis was reported. Conclusions: Our data indicate that the combination of docetaxel and nintedanib can be considered to be an effective treatment for EGFR TKI-resistant EGFR-mutant NSCLC.

langue originaleAnglais
Pages (de - à)2560-2567
Nombre de pages8
journalClinical and Translational Oncology
Volume23
Numéro de publication12
Les DOIs
étatPublié - 1 déc. 2021
Modification externeOui

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