Browsing by Author "Hahn, Olwen"

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    A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer: Cohort 36 of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART, SWOG S1609)
    (American Association for Cancer Research, 2022) Adams, Sylvia; Othus, Megan; Patel, Sandip Pravin; Miller, Kathy D.; Chugh, Rashmi; Schuetze, Scott M.; Chamberlin, Mary D.; Haley, Barbara J.; Storniolo, Anna Maria V.; Reddy, Mridula P.; Anderson, Scott A.; Zimmerman, Collin T.; O'Dea, Anne P.; Mirshahidi, Hamid R.; Ahnert, Jordi Rodon; Brescia, Frank J.; Hahn, Olwen; Raymond, Jane M.; Biggs, David D.; Connolly, Roisin M.; Sharon, Elad; Korde, Larissa A.; Gray, Robert J.; Mayerson, Edward; Plets, Melissa; Blanke, Charles D.; Chae, Young Kwang; Kurzrock, Razelle; Medicine, School of Medicine
    Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Patients and methods: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1 mg/kg i.v. every 6 weeks) plus nivolumab (240 mg i.v. every 2 weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: Overall, 17 evaluable patients enrolled. Median age was 60 years (26-85); median number of prior therapy lines was 2 (0-5). ORR was 18%; 3 of 17 patients achieved objective responses (1 complete, 2 partial responses; 2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+, and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AE), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE), with adrenal insufficiency observed in all 3 responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1, and absent tumor-infiltrating lymphocytes. Conclusions: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.
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    Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)
    (American Society of Clinical Oncology, 2022) Gnant, Michael; Dueck, Amylou C.; Frantal, Sophie; Martin, Miguel; Burstein, Hal J.; Greil, Richard; Fox, Peter; Wolff, Antonio C.; Chan, Arlene; Winer, Eric P.; Pfeiler, Georg; Miller, Kathy D.; Colleoni, Marco; Suga, Jennifer M.; Rubovsky, Gabor; Bliss, Judith M.; Mayer, Ingrid A.; Singer, Christian F.; Nowecki, Zbigniew; Hahn, Olwen; Thomson, Jacqui; Wolmark, Norman; Amillano, Kepa; Rugo, Hope S.; Steger, Guenther G.; Hernando Fernández de Aránguiz, Blanca; Haddad, Tufia C.; Perelló, Antonia; Bellet, Meritxell; Fohler, Hannes; Metzger Filho, Otto; Jallitsch-Halper, Anita; Solomon, Kadine; Schurmans, Céline; Theall, Kathy P.; Lu, Dongrui R.; Tenner, Kathleen; Fesl, Christian; DeMichele, Angela; Mayer, Erica L.; PALLAS groups and investigators; Medicine, School of Medicine
    Purpose: Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor-positive breast cancer has not been confirmed. Patients and methods: In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer-free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival. Results: Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial. Conclusion: At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor-positive breast cancer.
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    Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)
    (American Society of Clinical Oncology, 2016-08-01) Dickler, Maura N.; Barry, William T.; Cirrincione, Constance T.; Ellis, Matthew J.; Moynahan, Mary Ellen; Innocenti, Federico; Hurria, Arti; Rugo, Hope S.; Lake, Diana E.; Hahn, Olwen; Schneider, Bryan P.; Tripathy, Debasish; Carey, Lisa A.; Winer, Eric P.; Hudis, Clifford A.; Medicine, School of Medicine
    PURPOSE: To investigate whether anti-vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: Women with hormone receptor-positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned. RESULTS: From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%). CONCLUSION: The addition of bevacizumab to letrozole improved PFS in hormone receptor-positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting.