Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer
Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophy...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Breast |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977622001953 |
| _version_ | 1811166396939239424 |
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| author | Arlene Chan Manuel Ruiz-Borrego Gavin Marx A. Jo Chien Hope S. Rugo Adam Brufsky Michael Thirlwell Maureen Trudeau Ron Bose José A. García-Sáenz Daniel Egle Barbara Pistilli Johanna Wassermann Kerry A. Cheong Benjamin Schnappauf Dieter Semsek Christian F. Singer Navid Foruzan Daniel DiPrimeo Leanne McCulloch Sara A. Hurvitz Carlos H. Barcenas |
| author_facet | Arlene Chan Manuel Ruiz-Borrego Gavin Marx A. Jo Chien Hope S. Rugo Adam Brufsky Michael Thirlwell Maureen Trudeau Ron Bose José A. García-Sáenz Daniel Egle Barbara Pistilli Johanna Wassermann Kerry A. Cheong Benjamin Schnappauf Dieter Semsek Christian F. Singer Navid Foruzan Daniel DiPrimeo Leanne McCulloch Sara A. Hurvitz Carlos H. Barcenas |
| author_sort | Arlene Chan |
| collection | DOAJ |
| description | Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies. Methods: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L. Results: 563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed. Conclusions: These complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective. ClinicalTrials.gov registration number: NCT02400476. |
| first_indexed | 2024-04-10T15:51:41Z |
| format | Article |
| id | doaj.art-59dce946fa4342e6b9fbbf464f2e5a40 |
| institution | Directory Open Access Journal |
| issn | 1532-3080 |
| language | English |
| last_indexed | 2024-04-10T15:51:41Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Breast |
| spelling | doaj.art-59dce946fa4342e6b9fbbf464f2e5a402023-02-11T04:15:07ZengElsevierBreast1532-30802023-02-016794101Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancerArlene Chan0Manuel Ruiz-Borrego1Gavin Marx2A. Jo Chien3Hope S. Rugo4Adam Brufsky5Michael Thirlwell6Maureen Trudeau7Ron Bose8José A. García-Sáenz9Daniel Egle10Barbara Pistilli11Johanna Wassermann12Kerry A. Cheong13Benjamin Schnappauf14Dieter Semsek15Christian F. Singer16Navid Foruzan17Daniel DiPrimeo18Leanne McCulloch19Sara A. Hurvitz20Carlos H. Barcenas21Breast Cancer Research Centre-WA, Perth & Curtin University, Nedlands, Australia; Corresponding author. Breast Cancer Research Centre-WA, Perth & Curtin University, Nedlands, WA 6909, Australia.Hospital Universitario Virgen del Rocío, Seville, SpainSydney Adventist Hospital and Australian National University, Sydney, AustraliaUniversity of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USAUniversity of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USAMagee-Womens Hospital of UPMC, Pittsburgh, PA, USAMcGill University Health Centre, Montreal, QC, CanadaSunnybrook Health Sciences Centre, Toronto, ON, CanadaWashington University School of Medicine, St. Louis, MO, USAHospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), CIBERONC, Madrid, SpainMedical University Innsbruck, Innsbruck, AustriaGustave Roussy Cancer Center, Villejuif, FranceAPHP Sorbonne University, Pitié-Salpêtrière Hospital, Paris, FranceAdelaide Cancer Centre, Adelaide, AustraliaSana Klinikum Offenbach GmbH, Offenbach, GermanyPraxis am Diakonie Krankenhaus Onkologische Schwerpunktpraxis, Freiberg, GermanyMedical University of Vienna and Comprehensive Cancer Center, Vienna, AustriaPuma Biotechnology Inc., Los Angeles, CA, USAPuma Biotechnology Inc., Los Angeles, CA, USAPuma Biotechnology Inc., Los Angeles, CA, USAUniversity of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USAThe University of Texas MD Anderson Cancer Center, Houston, TX, USABackground: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies. Methods: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L. Results: 563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed. Conclusions: These complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective. ClinicalTrials.gov registration number: NCT02400476.http://www.sciencedirect.com/science/article/pii/S0960977622001953NeratinibTyrosine kinase inhibitorHER2-positiveBreast cancerEarly stageDiarrhea prophylaxis |
| spellingShingle | Arlene Chan Manuel Ruiz-Borrego Gavin Marx A. Jo Chien Hope S. Rugo Adam Brufsky Michael Thirlwell Maureen Trudeau Ron Bose José A. García-Sáenz Daniel Egle Barbara Pistilli Johanna Wassermann Kerry A. Cheong Benjamin Schnappauf Dieter Semsek Christian F. Singer Navid Foruzan Daniel DiPrimeo Leanne McCulloch Sara A. Hurvitz Carlos H. Barcenas Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer Breast Neratinib Tyrosine kinase inhibitor HER2-positive Breast cancer Early stage Diarrhea prophylaxis |
| title | Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer |
| title_full | Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer |
| title_fullStr | Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer |
| title_full_unstemmed | Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer |
| title_short | Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer |
| title_sort | final findings from the control trial strategies to reduce the incidence and severity of neratinib associated diarrhea in patients with her2 positive early stage breast cancer |
| topic | Neratinib Tyrosine kinase inhibitor HER2-positive Breast cancer Early stage Diarrhea prophylaxis |
| url | http://www.sciencedirect.com/science/article/pii/S0960977622001953 |
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