Browsing by Author "Marshall, Catherine H."

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    Differential Activity of PARP Inhibitors in BRCA1- Versus BRCA2-Altered Metastatic Castration-Resistant Prostate Cancer
    (American Society of Clinical Oncology, 2021-07-22) Taza, Fadi; Holler, Albert E.; Fu, Wei; Wang, Hao; Adra, Nabil; Albany, Costantine; Ashkar, Ryan; Cheng, Heather H.; Sokolova, Alexandra O.; Agarwal, Neeraj; Kessel, Adam; Bryce, Alan; Nafissi, Nellie; Barata, Pedro; Sartor, A. Oliver; Bastos, Diogo; Smaletz, Oren; Berchuck, Jacob E.; Taplin, Mary-Ellen; Aggarwal, Rahul; Sternberg, Cora N.; Vlachostergios, Panagiotis J.; Alva, Ajjai S.; Su, Christopher; Marshall, Catherine H.; Antonarakis, Emmanuel S.; Medicine, School of Medicine
    Two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and rucaparib) are US Food and Drug Administration-approved for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 mutations, but the relative efficacy of PARP inhibition in BRCA1- versus BRCA2-altered mCRPC is understudied. Methods: We conducted a multicenter retrospective analysis involving 12 sites. We collected genomic and clinical data from 123 patients with BRCA1/2-altered mCRPC who were treated with PARP inhibitors. The primary efficacy end point was the prostate-specific antigen (PSA) response (≥ 50% PSA decline) rate. Secondary end points were PSA progression-free survival (PSA-PFS), clinical or radiographic PFS, and overall survival. We compared clinical outcomes, and other genomic characteristics, among BRCA1- versus BRCA2-altered mCRPC. Results: A total of 123 patients (13 BRCA1 and 110 BRCA2) were included. PARP inhibitors used were olaparib (n = 116), rucaparib (n = 3), talazoparib (n = 2), and veliparib (n = 2). At diagnosis, 72% of patients had Gleason 8-10 disease. BRCA1 patients were more likely to have metastatic disease at presentation (69% v 37%; P = .04). Age, baseline PSA, metastatic distribution, and types of previous systemic therapies were similar between groups. There were equal proportions of germline mutations (51% v 46%; P = .78) in both groups. BRCA1 patients had more monoallelic (56% v 41%; P = .49) and concurrent TP53 (55% v 36%; P = .32) mutations. PSA50 responses in BRCA1- versus BRCA2-altered patients were 23% versus 63%, respectively (P = .01). BRCA2 patients achieved longer PSA-PFS (HR, 1.94; 95% CI, 0.92 to 4.09; P = .08), PFS (HR, 2.08; 95% CI, 0.99 to 4.40; P = .05), and overall survival (HR, 3.01; 95% CI, 1.32 to 6.83; P = .008). Biallelic (compared with monoallelic) mutations, truncating (compared with missense) mutations, and absence of a concurrent TP53 mutation were associated with PARP inhibitor sensitivity. Conclusion: PARP inhibitor efficacy is diminished in BRCA1- versus BRCA2-altered mCRPC. This is not due to an imbalance in germline mutations but might be related to more monoallelic mutations and/or concurrent TP53 alterations in the BRCA1 group.
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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.