Browsing by Author "Wesolowski, Robert"

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    A phase I study of talazoparib (BMN 673) combined with carboplatin and paclitaxel in patients with advanced solid tumors (NCI9782)
    (Wiley, 2022) Leal, Ticiana A.; Sharifi, Marina N.; Chan, Nancy; Wesolowski, Robert; Turk, Anita A.; Bruce, Justine Y.; O'Regan, Ruth M.; Eickhoff, Jens; Barroilhet, Lisa M.; Malhotra, Jyoti; Mehnert, Janice; Girda, Eugenia; Wiley, Elizabeth; Schmitz, Natalie; Andrews, Shannon; Liu, Glenn; Wisinski, Kari B.; Medicine, School of Medicine
    Background: Inhibitors of poly(ADP-ribose) polymerase (PARP) proteins potentiate antitumor activity of platinum chemotherapy. This study sought to determine the safety and tolerability of PARP inhibitor talazoparib with carboplatin and paclitaxel. Methods: We conducted a phase I study of talazoparib with carboplatin AUC5-6 and paclitaxel 80 mg/m2 days 1, 8, 15 of 21-day cycles in patients with advanced solid tumors. Patients enrolled using a 3 + 3 design in two cohorts with talazoparib for 7 (schedule A) or 3 days (schedule B). After induction with 4-6 cycles of triplet therapy, patients received one of three maintenance options: (a) continuation of triplet (b) carboplatin/talazoparib, or (c) talazoparib monotherapy. Results: Forty-three patients were treated. The MTD for both schedules was talazoparib 250mcg daily. The main toxicity was myelosuppression including grade 3/4 hematologic treatment-related adverse events (TRAEs). Dose modification occurred in 87% and 100% of patients for schedules A and B, respectively. Discontinuation due to TRAEs was 13% in schedule A and 10% in B. Ten out of 22 evaluable patients in schedule A and 5/16 patients in schedule B had a complete or partial response. Twelve out of 43 patients received ≥6 cycles of talazoparib after induction, with a 13-month median duration of maintenance. Conclusion: We have established the recommended phase II dose of Talazoparib at 250mcg on a 3- or 7-day schedule with carboplatin AUC6 and paclitaxel 80 mg/m2 on days 1, 8, 15 of 21-day cycles. This regimen is associated with significant myelosuppression, and in addition to maximizing supportive care, modification of the chemotherapy component would be a consideration for further development of this combination with the schedules investigated in this study.
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    A phase I study of talazoparib (BMN 673) combined with carboplatin and paclitaxel in patients with advanced solid tumors (NCI9782)
    (Wiley, 2022-11) Leal, Ticiana A.; Sharifi, Marina N.; Chan, Nancy; Wesolowski, Robert; Turk, Anita A.; Bruce, Justine Y.; O'Regan, Ruth M.; Eickhoff, Jens; Barroilhet, Lisa M.; Malhotra, Jyoti; Mehnert, Janice; Girda, Eugenia; Wiley, Elizabeth; Schmitz, Natalie; Andrews, Shannon; Liu, Glenn; Wisinski, Kari B.; Medicine, School of Medicine
    Background Inhibitors of poly(ADP‐ribose) polymerase (PARP) proteins potentiate antitumor activity of platinum chemotherapy. This study sought to determine the safety and tolerability of PARP inhibitor talazoparib with carboplatin and paclitaxel. Methods We conducted a phase I study of talazoparib with carboplatin AUC5‐6 and paclitaxel 80 mg/m2 days 1, 8, 15 of 21‐day cycles in patients with advanced solid tumors. Patients enrolled using a 3 + 3 design in two cohorts with talazoparib for 7 (schedule A) or 3 days (schedule B). After induction with 4–6 cycles of triplet therapy, patients received one of three maintenance options: (a) continuation of triplet (b) carboplatin/talazoparib, or (c) talazoparib monotherapy. Results Forty‐three patients were treated. The MTD for both schedules was talazoparib 250mcg daily. The main toxicity was myelosuppression including grade 3/4 hematologic treatment‐related adverse events (TRAEs). Dose modification occurred in 87% and 100% of patients for schedules A and B, respectively. Discontinuation due to TRAEs was 13% in schedule A and 10% in B. Ten out of 22 evaluable patients in schedule A and 5/16 patients in schedule B had a complete or partial response. Twelve out of 43 patients received ≥6 cycles of talazoparib after induction, with a 13‐month median duration of maintenance. Conclusion We have established the recommended phase II dose of Talazoparib at 250mcg on a 3‐ or 7‐day schedule with carboplatin AUC6 and paclitaxel 80 mg/m2 on days 1, 8, 15 of 21‐day cycles. This regimen is associated with significant myelosuppression, and in addition to maximizing supportive care, modification of the chemotherapy component would be a consideration for further development of this combination with the schedules investigated in this study.
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    Making National Cancer Institute-Designated Comprehensive Cancer Center Knowledge Accessible to Community Oncologists via an Online Tumor Board: Longitudinal Observational Study
    (JMIR, 2022-05-19) Kalra, Maitri; Henry, Elizabeth; McCann, Kelly; Karuturi, Meghan S.; Bustamante Alvarez, Jean G.; Parkes, Amanda; Wesolowski, Robert; Wei, Mei; Mougalian, Sarah S.; Durm, Gregory; Qin, Angel; Schonewolf, Caitlin; Trivedi, Meghna; Armaghani, Avan J.; Wilson, Frederick H.; Iams, Wade T.; Turk, Anita A.; Vikas, Praveen; Cecchini, Michael; Lubner, Sam; Pathak, Priyadarshini; Spencer, Kristen; Koshkin, Vadim S.; Labriola, Matthew K.; Marshall, Catherine H.; Beckermann, Katy E.; theMednet.org NCI-CCC Tumor Board Program Collaborative Group; Sharifi, Marina N.; Bejjani, Anthony C.; Hotchandani, Varsha; Housri, Samir; Housri, Nadine; Medicine, School of Medicine
    Background: Expert knowledge is often shared among multidisciplinary academic teams at tumor boards (TBs) across the country, but these conversations exist in silos and do not reach the wider oncology community. Objective: Using an oncologist-only question and answer (Q&A) website, we sought to document expert insights from TBs at National Cancer Institute-designated Comprehensive Cancer Centers (NCI-CCCs) to provide educational benefits to the oncology community. Methods: We designed a process with the NCI-CCCs to document and share discussions from the TBs focused on areas of practice variation on theMednet, an interactive Q&A website of over 13,000 US oncologists. The faculty translated the TB discussions into concise, non-case-based Q&As on theMednet. Answers were peer reviewed and disseminated in email newsletters to registered oncologists. Reach and engagement were measured. Following each Q&A, a survey question asked how the TB Q&As impacted the readers' practice. Results: A total of 23 breast, thoracic, gastrointestinal, and genitourinary programs from 16 NCI-CCC sites participated. Between December 2016 and July 2021, the faculty highlighted 368 questions from their TBs. Q&As were viewed 147,661 times by 7381 oncologists at 3515 institutions from all 50 states. A total of 277 (75%) Q&As were viewed every month. Of the 1063 responses to a survey question on how the Q&A affected clinicians' practices, 646 (61%) reported that it confirmed their current practice, 163 (20%) indicated that a Q&A would change their future practice, and 214 (15%) reported learning something new. Conclusions: Through an online Q&A platform, academics at the NCI-CCCs share knowledge outside the walls of academia with oncologists across the United States. Access to up-to-date expert knowledge can reassure clinicians' practices, significantly impact patient care in community practices, and be a source of new knowledge and education.