C E Geyer1, W M Sikov2, J Huober3, H S Rugo4, N Wolmark5, J O'Shaughnessy6, D Maag7, M Untch8, M Golshan9, J Ponce Lorenzo10, O Metzger11, M Dunbar7, W F Symmans12, P Rastogi13, J H Sohn14, R Young15, G S Wright16, C Harkness17, K McIntyre18, D Yardley19, S Loibl20. 1. National Surgical Adjuvant Breast and Bowel Project Foundation, Pittsburgh, USA; Houston Methodist Cancer Center, Houston, USA. Electronic address: cgeyer@houstonmethodist.org. 2. Women, Infants Hospital of Rhode Island, Providence, USA. 3. Breast Center Cantonal Hospital St Gallen, St Gallen, Switzerland. 4. University of California San Francisco Hellen Diller Family Comprehensive Cancer Center, San Francisco, USA. 5. National Surgical Adjuvant Breast and Bowel Project Foundation, Pittsburgh, USA; University of Pittsburgh, Pittsburgh, USA. 6. Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, USA; Baylor University Medical Center, Dallas, USA. 7. AbbVie Inc., North Chicago, USA. 8. HELIOS Klinikum Berlin-Buch, Berlin, Germany. 9. Yale Cancer Center, Yale School of Medicine, New Haven, USA. 10. University General Hospital of Alicante, ISABIAL, Alicante, Spain. 11. Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA. 12. Anderson Cancer Center, Houston, USA. 13. National Surgical Adjuvant Breast and Bowel Project Foundation, Pittsburgh, USA; UPMC Hillman Cancer Center/University of Pittsburgh, Pittsburgh, USA. 14. Yonsei University College of Medicine, Seoul, Korea. 15. Division of Breast Oncology, The Center for Cancer and Blood Disorders, Fort Worth, USA. 16. Florida Cancer Specialists and Sarah Cannon Research Institute, New Port Richey, USA. 17. Hope Women's Cancer Centers, Asheville, USA. 18. Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, USA. 19. Sarah Cannon Research Institute, Tennessee Oncology, Nashville, USA. 20. German Breast Group, c/o GBG Forschungs GmbH, Neu-Isenburg, Germany; Centre for Haematology and Oncology Bethanien, Frankfurt, Germany.
Abstract
BACKGROUND: Primary analyses of the phase III BrighTNess trial showed addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC). Here, we report 4.5-year follow-up data from the trial. PATIENTS AND METHODS: Women with untreated stage II-III TNBC were randomized (2 : 1 : 1) to paclitaxel (weekly for 12 doses) plus: (i) carboplatin (every 3 weeks for four cycles) plus veliparib (twice daily); (ii) carboplatin plus veliparib placebo; or (iii) carboplatin placebo plus veliparib placebo. All patients then received doxorubicin and cyclophosphamide every 2-3 weeks for four cycles. The primary endpoint was pCR. Secondary endpoints included event-free survival (EFS), overall survival (OS), and safety. Since the co-primary endpoint of increased pCR with carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel was not met, secondary analyses are descriptive. RESULTS: Of 634 patients, 316 were randomized to carboplatin plus veliparib with paclitaxel, 160 to carboplatin with paclitaxel, and 158 to paclitaxel. With median follow-up of 4.5 years, the hazard ratio for EFS for carboplatin plus veliparib with paclitaxel versus paclitaxel was 0.63 [95% confidence interval (CI) 0.43-0.92, P = 0.02], but 1.12 (95% CI 0.72-1.72, P = 0.62) for carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel. In post hoc analysis, the hazard ratio for EFS was 0.57 (95% CI 0.36-0.91, P = 0.02) for carboplatin with paclitaxel versus paclitaxel. OS did not differ significantly between treatment arms, nor did rates of myelodysplastic syndromes, acute myeloid leukemia, or other secondary malignancies. CONCLUSIONS: Improvement in pCR with the addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without increasing the risk of second malignancies, whereas adding veliparib did not impact EFS. These findings support the addition of carboplatin to weekly paclitaxel followed by doxorubicin and cyclophosphamide neoadjuvant chemotherapy for early-stage TNBC.
BACKGROUND: Primary analyses of the phase III BrighTNess trial showed addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC). Here, we report 4.5-year follow-up data from the trial. PATIENTS AND METHODS: Women with untreated stage II-III TNBC were randomized (2 : 1 : 1) to paclitaxel (weekly for 12 doses) plus: (i) carboplatin (every 3 weeks for four cycles) plus veliparib (twice daily); (ii) carboplatin plus veliparib placebo; or (iii) carboplatin placebo plus veliparib placebo. All patients then received doxorubicin and cyclophosphamide every 2-3 weeks for four cycles. The primary endpoint was pCR. Secondary endpoints included event-free survival (EFS), overall survival (OS), and safety. Since the co-primary endpoint of increased pCR with carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel was not met, secondary analyses are descriptive. RESULTS: Of 634 patients, 316 were randomized to carboplatin plus veliparib with paclitaxel, 160 to carboplatin with paclitaxel, and 158 to paclitaxel. With median follow-up of 4.5 years, the hazard ratio for EFS for carboplatin plus veliparib with paclitaxel versus paclitaxel was 0.63 [95% confidence interval (CI) 0.43-0.92, P = 0.02], but 1.12 (95% CI 0.72-1.72, P = 0.62) for carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel. In post hoc analysis, the hazard ratio for EFS was 0.57 (95% CI 0.36-0.91, P = 0.02) for carboplatin with paclitaxel versus paclitaxel. OS did not differ significantly between treatment arms, nor did rates of myelodysplastic syndromes, acute myeloid leukemia, or other secondary malignancies. CONCLUSIONS: Improvement in pCR with the addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without increasing the risk of second malignancies, whereas adding veliparib did not impact EFS. These findings support the addition of carboplatin to weekly paclitaxel followed by doxorubicin and cyclophosphamide neoadjuvant chemotherapy for early-stage TNBC.
Authors: Nina Ditsch; Achim Wöcke; Michael Untch; Christian Jackisch; Ute-Susann Albert; Maggie Banys-Paluchowski; Ingo Bauerfeind; Jens-Uwe Blohmer; Wilfried Budach; Peter Dall; Eva Maria Fallenberg; Peter A Fasching; Tanja N Fehm; Michael Friedrich; Bernd Gerber; Oleg Gluz; Nadia Harbeck; Jörg Heil; Jens Huober; Hans H Kreipe; David Krug; Thorsten Kühn; Sherko Kümmel; Cornelia Kolberg-Liedtke; Sibylle Loibl; Diana Lüftner; Michael Patrick Lux; Nicolai Maass; Christoph Mundhenke; Ulrike Nitz; Tjoung-Won Park-Simon; Toralf Reimer; Kerstin Rhiem; Achim Rody; Marcus Schmidt; Andreas Schneeweiss; Florian Schütz; Hans-Peter Sinn; Christine Solbach; Erich-Franz Solomayer; Elmar Stickeler; Christoph Thomssen; Isabell Witzel; Volkmar Müller; Wolfgang Janni; Marc Thill Journal: Breast Care (Basel) Date: 2022-05-05 Impact factor: 2.268
Authors: Neha Pathak; Aparna Sharma; Arunmozhimaran Elavarasi; Jeeva Sankar; S V S Deo; Daya N Sharma; Sandeep Mathur; Sudhir Kumar; Chandra P Prasad; Akash Kumar; Atul Batra Journal: Breast Date: 2022-04-15 Impact factor: 4.254