Jasgit C Sachdev1,2, Pamela Munster3, Donald W Northfelt4, Hyo Sook Han5, Cynthia Ma6, Fiona Maxwell7, Tiffany Wang8, Bruce Belanger8, Bin Zhang8, Yan Moore8, Arunthathi Thiagalingam8, Carey Anders9. 1. HonorHealth Research Institute, 10510 N. 92nd Street, Suite 200, Scottsdale, AZ, 85258, USA. Jasgit.Sachdev@HonorHealth.com. 2. Translational Genomics Research Institute, Phoenix, AZ, USA. Jasgit.Sachdev@HonorHealth.com. 3. University of California, San Francisco, CA, USA. 4. Mayo Clinic Hospital, Phoenix, AZ, USA. 5. Moffitt Cancer Center, Tampa, FL, USA. 6. Washington University, St. Louis, MO, USA. 7. Ipsen, Abingdon, UK. 8. Ipsen, Cambridge, MA, USA. 9. Duke Cancer Institute, Durham, NC, USA.
Abstract
PURPOSE: Metastatic breast cancer (mBC) remains incurable and is associated with low survival rates. This study assessed the efficacy and safety of liposomal irinotecan in heavily pretreated patients with mBC, with or without active brain metastases (BM). METHODS: Following the dose escalation phase and determination of recommended phase 2 dose, the expansion phase of this phase I, open-label, non-randomized study, assigned adult women to cohorts based on mBC subtype: cohort 1, hormone receptor +/human epidermal growth factor receptor 2-; cohort 2, triple-negative breast cancer; or cohort 3, any mBC subtype with active BM. Patients received liposomal irinotecan 50 or 70 mg/m2 free base every 2 weeks. Here, we report secondary outcomes including best overall response (BOR), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). RESULTS: For non-central nervous system (non-CNS) disease across all cohorts (intent-to-treat population, N = 29), the ORR was 34.5% (95% confidence interval: 17.94-54.33), with a BOR of partial response in 10 patients (34.5%), stable disease in five (17.2%), progressive disease in 10 (34.5%); four patients were unevaluable (13.8%). The ORR for the CNS cohort was 30.0% (95% confidence interval: 6.67-65.25) using modified Response Evaluation Criteria in Solid Tumors. Common grade 3 or higher TEAEs were diarrhea (27.6%), nausea (17.2%), fatigue (13.8%), asthenia (10.3%), and hypokalemia (10.3%). Serious treatment-related TEAEs were reported in six patients (20.7%). No treatment-related TEAEs resulted in death. CONCLUSIONS: Liposomal irinotecan monotherapy demonstrated antitumor activity in heavily pretreated patients with mBC, with or without BM. The observed safety profile was consistent with that in previous studies. CLINICAL TRIAL REGISTRATION: Trial registration ID NCT01770353.
PURPOSE:Metastatic breast cancer (mBC) remains incurable and is associated with low survival rates. This study assessed the efficacy and safety of liposomal irinotecan in heavily pretreated patients with mBC, with or without active brain metastases (BM). METHODS: Following the dose escalation phase and determination of recommended phase 2 dose, the expansion phase of this phase I, open-label, non-randomized study, assigned adult women to cohorts based on mBC subtype: cohort 1, hormone receptor +/humanepidermal growth factor receptor 2-; cohort 2, triple-negative breast cancer; or cohort 3, any mBC subtype with active BM. Patients received liposomal irinotecan 50 or 70 mg/m2 free base every 2 weeks. Here, we report secondary outcomes including best overall response (BOR), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). RESULTS: For non-central nervous system (non-CNS) disease across all cohorts (intent-to-treat population, N = 29), the ORR was 34.5% (95% confidence interval: 17.94-54.33), with a BOR of partial response in 10 patients (34.5%), stable disease in five (17.2%), progressive disease in 10 (34.5%); four patients were unevaluable (13.8%). The ORR for the CNS cohort was 30.0% (95% confidence interval: 6.67-65.25) using modified Response Evaluation Criteria in Solid Tumors. Common grade 3 or higher TEAEs were diarrhea (27.6%), nausea (17.2%), fatigue (13.8%), asthenia (10.3%), and hypokalemia (10.3%). Serious treatment-related TEAEs were reported in six patients (20.7%). No treatment-related TEAEs resulted in death. CONCLUSIONS: Liposomal irinotecan monotherapy demonstrated antitumor activity in heavily pretreated patients with mBC, with or without BM. The observed safety profile was consistent with that in previous studies. CLINICAL TRIAL REGISTRATION: Trial registration ID NCT01770353.
Entities:
Keywords:
Brain metastases; Heavily pretreated patients; Liposomal irinotecan; Metastatic breast cancer; Objective response rate; Phase I clinical trial
Authors: G P Stathopoulos; D Tsavdaridis; N A Malamos; S K Rigatos; Ch Kosmas; N Pergantas; J G Stathopoulos; J Xynotroulas Journal: Cancer Chemother Pharmacol Date: 2005-05-03 Impact factor: 3.333
Authors: Helen Lee; Anthony F Shields; Barry A Siegel; Kathy D Miller; Ian Krop; Cynthia X Ma; Patricia M LoRusso; Pamela N Munster; Karen Campbell; Daniel F Gaddy; Shannon C Leonard; Elena Geretti; Stephanie J Blocker; Dmitri B Kirpotin; Victor Moyo; Thomas J Wickham; Bart S Hendriks Journal: Clin Cancer Res Date: 2017-03-15 Impact factor: 12.531
Authors: Edith A Perez; David W Hillman; James A Mailliard; James N Ingle; J Michael Ryan; Tom R Fitch; Kendrith M Rowland; Carl G Kardinal; James E Krook; John W Kugler; Shaker R Dakhil Journal: J Clin Oncol Date: 2004-07-15 Impact factor: 44.544
Authors: Charles O Noble; Michal T Krauze; Daryl C Drummond; John Forsayeth; Mark E Hayes; Janine Beyer; Piotr Hadaczek; Mitchel S Berger; Dmitri B Kirpotin; Krystof S Bankiewicz; John W Park Journal: Nanomedicine (Lond) Date: 2014-02-04 Impact factor: 5.307
Authors: Pin-Yuan Chen; Tomoko Ozawa; Daryl C Drummond; Ashish Kalra; Jonathan B Fitzgerald; Dmitri B Kirpotin; Kuo-Chen Wei; Nicholas Butowski; Michael D Prados; Mitchel S Berger; John R Forsayeth; Krystof Bankiewicz; C David James Journal: Neuro Oncol Date: 2012-12-21 Impact factor: 12.300
Authors: B S Adiwijaya; J Kim; I Lang; T Csõszi; A Cubillo; J-S Chen; M Wong; J O Park; J S Kim; K M Rau; B Melichar; J B Gallego; J Fitzgerald; B Belanger; I Molnar; W W Ma Journal: Clin Pharmacol Ther Date: 2017-06-05 Impact factor: 6.875
Authors: Rachel A Freedman; Rebecca S Gelman; Carey K Anders; Michelle E Melisko; Heather A Parsons; Anne M Cropp; Kelly Silvestri; Christine M Cotter; Kathryn P Componeschi; Juan M Marte; Roisin M Connolly; Beverly Moy; Catherine H Van Poznak; Kimberly L Blackwell; Shannon L Puhalla; Rachel C Jankowitz; Karen L Smith; Nuhad Ibrahim; Timothy J Moynihan; Ciara C O'Sullivan; Julie Nangia; Polly Niravath; Nadine Tung; Paula R Pohlmann; Robyn Burns; Mothaffar F Rimawi; Ian E Krop; Antonio C Wolff; Eric P Winer; Nancy U Lin Journal: J Clin Oncol Date: 2019-03-12 Impact factor: 44.544