PMID- 34292495 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20220207 IS - 1699-3055 (Electronic) IS - 1699-048X (Linking) VI - 23 IP - 12 DP - 2021 Dec TI - Efficacy of nintedanib plus docetaxel in patients with refractory advanced epidermal growth factor receptor mutant lung adenocarcinoma. PG - 2560-2567 LID - 10.1007/s12094-021-02661-2 [doi] AB - 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/m(2)/3 weeks to 16 patients, at 60 mg/m(2) to 2 patients and at 45 mg/m(2) 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. CI - (c) 2021. Federacion de Sociedades Espanolas de Oncologia (FESEO). FAU - Riudavets, Mariona AU - Riudavets M AD - Medical Oncology Department, Hospital de La Santa Creu I Sant Pau, Sant Quinti, 89, 08041, Barcelona, Spain. FAU - Bosch-Barrera, Joaquim AU - Bosch-Barrera J AD - Medical Oncology Department, Institut Catala d'Oncologia (ICO), Hospital Universitari Dr. Josep Trueta, Girona, Spain. FAU - Cabezon-Gutierrez, Luis AU - Cabezon-Gutierrez L AD - Medical Oncology Department, Hospital Universitario de Torrejon, Madrid, Spain. FAU - Diz Tain, Pilar AU - Diz Tain P AD - Medical Oncology Department, Complejo Asistencial Universitario de Leon, Leon, Spain. FAU - Hernandez, Ainhoa AU - Hernandez A AD - Medical Oncology Department, Institut Catala d'Oncologia (ICO), Badalona Applied Research Group in Oncology (B-ARGO Group), Institut Investigacio Germans Trias I Pujol (IGTP), Department of Medicine, Universitat Autonoma de Barcelona (UAB), Campus Can Ruti, Badalona, Barcelona, Spain. FAU - Alonso, Miriam AU - Alonso M AD - Medical Oncology Department, Hospital Universitario Virgen del Rocio, Sevilla, Spain. FAU - Blanco, Remei AU - Blanco R AD - Medical Oncology Department, Consorci Sanitari de Terrassa, Barcelona, Spain. FAU - Galvez, Elisa AU - Galvez E AD - Medical Oncology Department, Hospital General de Elda, Alicante, Spain. FAU - Insa, Amelia AU - Insa A AD - Medical Oncology Department, Hospital Clinico Universitario de Valencia, Valencia, Spain. FAU - Mielgo, Xabier AU - Mielgo X AD - Medical Oncology Department, Fundacion Hospital Universitario de Alcorcon, Madrid, Spain. FAU - Moran, Teresa AU - Moran T AD - Medical Oncology Department, Institut Catala d'Oncologia (ICO), Badalona Applied Research Group in Oncology (B-ARGO Group), Institut Investigacio Germans Trias I Pujol (IGTP), Department of Medicine, Universitat Autonoma de Barcelona (UAB), Campus Can Ruti, Badalona, Barcelona, Spain. FAU - Ponce, Santiago AU - Ponce S AD - Medical Oncology Department, Hospital Universitario, 12 de Octubre, Madrid, Spain. FAU - Roa, Diana AU - Roa D AD - Medical Oncology Department, Hospital de Manacor, Manacor, Spain. FAU - Sanchez, Jose Miguel AU - Sanchez JM AD - Medical Oncology Department, Hospital Universitario de la Princesa, Madrid, Spain. FAU - Majem, Margarita AU - Majem M AUID- ORCID: 0000-0002-9919-7485 AD - Medical Oncology Department, Hospital de La Santa Creu I Sant Pau, Sant Quinti, 89, 08041, Barcelona, Spain. mmajem@santpau.cat. LA - eng PT - Journal Article DEP - 20210722 PL - Italy TA - Clin Transl Oncol JT - Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico JID - 101247119 RN - 0 (Biomarkers, Tumor) RN - 0 (Indoles) RN - 15H5577CQD (Docetaxel) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - G6HRD2P839 (nintedanib) SB - IM MH - Adenocarcinoma of Lung/*drug therapy/genetics/pathology MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Biomarkers, Tumor/*genetics MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology MH - Docetaxel/administration & dosage MH - ErbB Receptors/genetics MH - Female MH - Follow-Up Studies MH - Humans MH - Indoles/administration & dosage MH - Lung Neoplasms/*drug therapy/genetics/pathology MH - Male MH - Middle Aged MH - *Mutation MH - Prognosis MH - Retrospective Studies MH - Survival Rate OTO - NOTNLM OT - Docetaxel OT - Epidermal growth factor receptor (EGFR) OT - Nintedanib OT - Non-small cell lung cancer EDAT- 2021/07/23 06:00 MHDA- 2022/02/08 06:00 CRDT- 2021/07/22 12:32 PHST- 2021/04/02 00:00 [received] PHST- 2021/06/03 00:00 [accepted] PHST- 2021/07/23 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/07/22 12:32 [entrez] AID - 10.1007/s12094-021-02661-2 [pii] AID - 10.1007/s12094-021-02661-2 [doi] PST - ppublish SO - Clin Transl Oncol. 2021 Dec;23(12):2560-2567. doi: 10.1007/s12094-021-02661-2. Epub 2021 Jul 22.