M R Hall1, H-M Dehbi2, S Banerjee3, R Lord4, A Clamp5, J A Ledermann6, S Nicum7, R Lilleywhite8, R Bowen9, A Michael10, A Feeney11, R Glasspool12, A Hackshaw13, G Rustin14. 1. Mount Vernon Cancer Centre, Northwood, UK. Electronic address: Marcia.hall@nhs.net. 2. Comprehensive Clinical Trials Unit at UCL, London, UK. Electronic address: h.dehbi@ucl.ac.uk. 3. Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK. Electronic address: Susana.banerjee@rmh.nhs.uk. 4. Clatterbridge Cancer Centre, Liverpool, UK. Electronic address: Rosemary.lord@clatterbridgecc.nhs.uk. 5. The Christie NHS Foundation Trust and University of Manchester, UK. Electronic address: Andrew.clamp@christie.nhs.uk. 6. Cancer Research UK & UCL Cancer Trials Centre, London, UK. Electronic address: j.ledermann@ucl.ac.uk. 7. Churchill Hospital, Oxford, UK. Electronic address: snicum@nhs.net. 8. Cancer Research UK & UCL Cancer Trials Centre, London, UK. Electronic address: r.e.lillywhite@bham.ac.uk. 9. Royal United Hospital, Bath, UK. Electronic address: Rebecca.bowen3@nhs.net. 10. Royal Surrey County Hospital, Guildford, UK. Electronic address: a.michael@surrey.ac.uk. 11. Cancer Research UK & UCL Cancer Trials Centre, London, UK. Electronic address: a.feeney@ucl.ac.uk. 12. Beatson Institute, Glasgow, UK. Electronic address: ros.glasspool@ggc.scot.nhs.uk. 13. Cancer Research UK & UCL Cancer Trials Centre, London, UK. Electronic address: a.hackshaw@ucl.ac.uk. 14. Mount Vernon Cancer Centre, Northwood, UK. Electronic address: grustin@nhs.net.
Abstract
BACKGROUND: We investigated the safety and efficacy of a combination of the oral tyrosine kinase inhibitor, nintedanib (BIBF 1120) with oral cyclophosphamide in patients with relapsed ovarian cancer. PATIENTS AND METHODS: Patients with relapsed ovarian, fallopian tube or primary peritoneal cancer received oral cyclophosphamide (100 mg o.d.) and were randomised (1,1) to also have either oral nintedanib or placebo. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), response rate, toxicity, and quality of life. RESULTS: 117 patients were randomised, 3 did not start trial treatment, median age 64 years. Forty-five (39%) had received ≥5 lines chemotherapy. 30% had received prior bevacizumab. The median OS was 6.8 (nintedanib) versus 6.4 (placebo) months (hazard ratio 1.08; 95% confidence interval 0.72-1.62; P = 0.72). The 6-month PFS rate was 29.6% versus 22.8% (P = 0.57). Grade 3/4 adverse events occurred in 64% (nintedanib) versus 54% (placebo) of patients (P = 0.28); the most frequent G3/4 toxicities were lymphopenia (18.6% nintedanib versus 16.4% placebo), diarrhoea (13.6% versus 0%), neutropenia (11.9% versus 0%), fatigue (10.2% versus 9.1%), and vomiting (10.2% versus 7.3%). Patients who had received prior bevacizumab treatment had 52 days less time on treatment (P < 0.01). 26 patients (23%) took oral cyclophosphamide for ≥6 months. There were no differences in quality of life between treatment arms. CONCLUSIONS: This is the largest reported cohort of patients with relapsed ovarian cancer treated with oral cyclophosphamide. Nintedanib did not improve outcomes when added to oral cyclophosphamide. Although not significant, more patients than expected remained on treatment for ≥6 months. This may reflect a higher proportion of patients with more indolent disease or the higher dose of cyclophosphamide used. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT01610869.
BACKGROUND: We investigated the safety and efficacy of a combination of the oral tyrosine kinase inhibitor, nintedanib (BIBF 1120) with oral cyclophosphamide in patients with relapsed ovarian cancer. PATIENTS AND METHODS: Patients with relapsed ovarian, fallopian tube or primary peritoneal cancer received oral cyclophosphamide (100 mg o.d.) and were randomised (1,1) to also have either oral nintedanib or placebo. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), response rate, toxicity, and quality of life. RESULTS: 117 patients were randomised, 3 did not start trial treatment, median age 64 years. Forty-five (39%) had received ≥5 lines chemotherapy. 30% had received prior bevacizumab. The median OS was 6.8 (nintedanib) versus 6.4 (placebo) months (hazard ratio 1.08; 95% confidence interval 0.72-1.62; P = 0.72). The 6-month PFS rate was 29.6% versus 22.8% (P = 0.57). Grade 3/4 adverse events occurred in 64% (nintedanib) versus 54% (placebo) of patients (P = 0.28); the most frequent G3/4 toxicities were lymphopenia (18.6% nintedanib versus 16.4% placebo), diarrhoea (13.6% versus 0%), neutropenia (11.9% versus 0%), fatigue (10.2% versus 9.1%), and vomiting (10.2% versus 7.3%). Patients who had received prior bevacizumab treatment had 52 days less time on treatment (P < 0.01). 26 patients (23%) took oral cyclophosphamide for ≥6 months. There were no differences in quality of life between treatment arms. CONCLUSIONS: This is the largest reported cohort of patients with relapsed ovarian cancer treated with oral cyclophosphamide. Nintedanib did not improve outcomes when added to oral cyclophosphamide. Although not significant, more patients than expected remained on treatment for ≥6 months. This may reflect a higher proportion of patients with more indolent disease or the higher dose of cyclophosphamide used. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT01610869.
Authors: Igor Maiborodin; Alfija Mansurova; Alexander Chernyavskiy; Alexander Romanov; Vladimir Voitcitctkii; Anna Kedrova; Alexander Tarkhov; Alena Chernyshova; Sergey Krasil'nikov Journal: J Pers Med Date: 2022-02-22