Abstract 3587
Background
The SENECA trial, a phase IIb, open label, multicentre study, aimed to investigate in the real life efficacy and safety of nintedanib plus docetaxel, used weekly (T1) or q3wks (T2), in pretreated nsNSCLC patients, stratified for relapse-timing (within or over 3 months from end of first-line therapy). Preliminary efficacy data have been previously presented: no difference in median Progression Free-Survival and a similar trend in Overall Survival between T1 and T2 were showed. Weekly docetaxel has better tolerability than q3wks administration: aim of this study is to evaluate two different docetaxel schedules combined with nintedanib, in order to potentially maximize their use.
Methods
Baseline characteristics have been already presented. Incidence and severity of treatment-related Adverse Events (AEs) were evaluated from beginning of treatment until 28 days after its completion, according to Common Terminology Criteria for Adverse Events (CTCAE) version 3, in 167 patients (receiving at least one dose of study drugs) enrolled in 18 Italian oncologic centres, between January 2016 and March 2018.
Results
Incidence of any grades AEs was numerically higher in T2 compared to T1 (484 vs 450 events, respectively); a complete overview of AEs (≥ 5% incidence in either group) is reassumed in Table1. Docetaxel was reduced in 14.4% patients, more frequently in T2 vs T1 (18.8% vs 9.7%). Nintedanib reduction was needed in 19.8% of patients, 23.2% in T1 and 15.3% in T2, mainly for diarrhea. Thirty-one (18.6%) patients permanently discontinued study drugs (11 in T1 vs 20 in T2) due to hypersensitivity reactions and pain.Table: 1404P
Main AEs observed in the SENECA trial according to docetaxel schedule and CTCAE grade
| N = 167 | ||||||
|---|---|---|---|---|---|---|
| AEs | T1 (N = 82) | T2 (N = 85) | p- value | T1 (N = 82) | T2 (N = 85) | p- value |
| Any Grades | Grade ≥ 3 | |||||
| Fatigue | 44(53.6%) | 56(65.9%) | 0.10 | 5(6.1%) | 10(11.7%) | 0.20 |
| Diarrhea | 41(50%) | 40(47%) | 0.70 | 4(4.8%) | 4(4.7%) | 0.95 |
| ALT elevation | 24(29.3%) | 17(20%) | 0.16 | 4(4.8%) | 5(5.9%) | 0.77 |
| Afebrile Neutropenia | 11(13.4%) | 45(52.9%) | <0.0001 | 3(3.6%) | 17(20%) | <0.0001 |
| Pain | 19(23.2%) | 21(24.7%) | 0.81 | 3(3.6%) | 2(2.3%) | 0.62 |
| Anemia | 18(21.9%) | 16(18.8%) | 0.61 | 1(1.2%) | 1(1.2%) | 0.30 |
| Nausea | 17(20.7%) | 14(16.5%) | 0.47 | 3(3.6%) | 3(3.5%) | 0.96 |
| Dyspnea | 16(19.5%) | 18(21.2%) | 0.78 | 2(2.4%) | 2(2.3%) | 0.97 |
| Fever | 15(18.3%) | 9(10.6%) | 0.15 | 2(2.4%) | 0(0%) | 0.14 |
| Cough | 13(15.8%) | 14(16.5%) | 0.91 | 0(0%) | 0(0%) | NE |
| Decreased Platelets | 11(13.4%) | 2(2.3%) | 0.007 | 0(0%) | 0(0%) | NE |
| Skin Toxicity | 11(13.4%) | 9(10.6%) | 0.57 | 0(0%) | 1(1.2%) | 0.32 |
| Oral Mucositis | 10(12.2%) | 19(22.3%) | 0.08 | 3(3.6%) | 1(1.2%) | 0.29 |
| GGT elevation | 9(11%) | 10(11.8%) | 0.87 | 3(3.6%) | 5(5.9%) | 0.50 |
| Vomiting | 7(8.5%) | 15(17.6%) | 0.08 | 0(0%) | 1(1.2%) | 0.32 |
| Decreased leukocytes | 5(6.1%) | 10(11.8%) | 0.20 | 0(0%) | 2(2.3%) | 0.16 |
| AST elevation | 6(7.3%) | 6(7%) | 0.94 | 2(2.4%) | 1(1.2%) | 0.53 |
| Dysgeusia | 6(7.3%) | 5(5.9%) | 0.70 | 0(0%) | 0(0%) | NE |
| Parestesie | 4(4.9%) | 1(1.2%) | 0.38 | 7(8.5%) | 0(0%) | 0.97 |
ALT: alanine aminotrasferase; NE: not evaluable; AST: aspartate aminotransferase; GGT: gamma-glutamyltransferase.
Conclusions
Preliminary safety data of SENECA trial show statistically significant differences only in a few of the items explored (particularly afebrile neutropenia), but underline a clear trend of higher tolerability for weekly docetaxel combination treatment in second line nsNSCLC patients.
Clinical trial identification
EudraCT: 2014-005016-42.
Legal entity responsible for the study
Department of Oncology, University of Turin.
Funding
Department of Oncology- University of Turin.
Editorial Acknowledgement
Disclosure
A. Morabito: Honoraria: Roche, AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, BMS. F. Grossi: Advisory boards and lectures: Boehringer Ingelheim, MSD, BMS, AstraZeneca; Lectures: Lilly, Celgene, Amgen, Roche. V. Scotti: Advisory boards and speaker's fee: BI S. Novello: Speakers’ bureau: BI, AstraZeneca, Roche, MSD, BMS, Ely Lilly, Takeda, Pfizer. All other authors have declared no conflicts of interest.