scispace - formally typeset
Search or ask a question
Author

Mary K. Buss

Bio: Mary K. Buss is an academic researcher from Beth Israel Deaconess Medical Center. The author has contributed to research in topics: Palliative care & Medicine. The author has an hindex of 26, co-authored 68 publications receiving 2981 citations. Previous affiliations of Mary K. Buss include Harvard University & Brigham and Women's Hospital.


Papers
More filters
Journal ArticleDOI
Robert L. Coleman1, Amit M. Oza2, Domenica Lorusso, Carol Aghajanian3, Ana Oaknin4, Andrew Dean, Nicoletta Colombo5, Johanne I Weberpals6, Andrew R Clamp7, Giovanni Scambia8, Alexandra Leary9, Robert W Holloway, Margarita Amenedo Gancedo, Peter C.C. Fong10, Jeffrey C. Goh11, David M. O'Malley12, Deborah K. Armstrong13, Jesus Garcia-Donas, Elizabeth M. Swisher14, Anne Floquet, Gottfried E. Konecny15, Iain A. McNeish16, Clare L. Scott17, Terri Cameron, Lara Maloney, Jeff Isaacson, Sandra Goble, Caroline Grace, Thomas Harding, Mitch Raponi, James Sun18, Kevin K. Lin, Heidi Giordano, Jonathan A. Ledermann19, Martin Buck, A Dean, Michael Friedlander, J C Goh11, Paul R. Harnett, G Kichenadasse20, C L Scott17, H Denys, Luc Dirix, Ignace Vergote, Laurie Elit, Prafull Ghatage, Amit M. Oza2, Marie Plante, Diane Provencher, J I Weberpals6, Stephen Welch, A Floquet, Laurence Gladieff, Florence Joly, A Leary9, Alain Lortholary, Jean-Pierre Lotz, J. Medioni, Olivier Tredan, Benoit You, A El-Balat, C Hänle, P Krabisch, T Neunhöffer, M Pölcher, Pauline Wimberger, Amnon Amit, S Kovel, M Leviov, Tamar Safra, Ronnie Shapira-Frommer, Salomon M. Stemmer, Alessandra Bologna, N Colombo5, Domenica Lorusso, Sandro Pignata, Roberto Sabbatini, G Scambia8, Stefano Tamberi, Claudio Zamagni, P C Fong10, A O'Donnell, M Amenedo Gancedo, A Casado Herraez, J Garcia-Donas, E M Guerra, A Oaknin4, I Palacio, Iris L. Romero, A Sanchez, Susana Banerjee, A Clamp7, Y Drew, Hani Gabra, D Jackson, Jonathan A. Ledermann19, I A McNeish16, Christine Parkinson, Melanie E Powell, C Aghajanian3, D K Armstrong13, Michael J. Birrer, Mary K. Buss, Setsuko K. Chambers, L-m Chen, Robert L. Coleman1, R W Holloway, G E Konecny15, L Ma, Mark A. Morgan, R T Morris, David G. Mutch, D M O'Malley12, B M Slomovitz, E M Swisher14, T Vanderkwaak, M Vulfovich 
TL;DR: This trial assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity.

1,139 citations

Journal ArticleDOI
TL;DR: Cediranib plus olaparib seems to improve PFS in women with recurrent platinum-sensitive high-grade serous or endometrioid ovarian cancer, and warrants study in a phase 3 trial.
Abstract: Summary Background Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is an anti-angiogenic agent with activity against VEGF receptor (VEGFR) 1, VEGFR2, and VEGFR3. Both oral agents have antitumour activity in women with recurrent ovarian cancer, and their combination was active and had manageable toxicities in a phase 1 trial. We investigated whether this combination could improve progression-free survival (PFS) compared with olaparib monotherapy in women with recurrent platinum-sensitive ovarian cancer. Methods In our randomised, open-label, phase 2 study, we recruited women (aged ≥18 years) who had measurable platinum-sensitive, relapsed, high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer, or those with deleterious germline BRCA1 /2 mutations from nine participating US academic medical centres. We randomly allocated participants (1:1) according to permuted blocks, stratified by germline BRCA status and previous anti-angiogenic therapy, to receive olaparib capsules 400 mg twice daily or the combination at the recommended phase 2 dose of cediranib 30 mg daily and olaparib capsules 200 mg twice daily. The primary endpoint was progression-free survival analysed in the intention-to-treat population. The phase 2 trial is no longer accruing patients. An interim analysis was conducted in November, 2013, after 50% of expected events had occurred and efficacy results were unmasked. The primary analysis was performed on March 31, 2014, after 47 events (66% of those expected). The trial is registered with ClinicalTrials.gov, number NCT01116648. Findings Between Oct 26, 2011, and June 3, 2013, we randomly allocated 46 women to receive olaparib alone and 44 to receive the combination of olaparib and cediranib. Median PFS was 17·7 months (95% CI 14·7–not reached) for the women treated with cediranib plus olaparib compared with 9·0 months (95% CI 5·7–16·5) for those treated with olaparib monotherapy (hazard ratio 0·42, 95% CI 0·23–0·76; p=0·005). Grade 3 and 4 adverse events were more common with combination therapy than with monotherapy, including fatigue (12 patients in the cediranib plus olaparib group vs five patients in the olaparib monotherapy group), diarrhoea (ten vs none), and hypertension (18 vs none). Interpretation Cediranib plus olaparib seems to improve PFS in women with recurrent platinum-sensitive high-grade serous or endometrioid ovarian cancer, and warrants study in a phase 3 trial. The side-effect profile suggests such investigations should include assessments of quality of life and patient-reported outcomes to understand the effects of a continuing oral regimen with that of intermittent chemotherapy. Funding American Recovery and Reinvestment Act grant from the National Institutes of Health (NIH) (3 U01 CA062490-16S2); Intramural Program of the Center for Cancer Research; and the Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH.

497 citations

Journal ArticleDOI
TL;DR: The observed activity provides preliminary clinical evidence of synergism between olaparib and alpelisib, particularly in epithelial ovarian cancer, and warrants further investigation.
Abstract: Summary Background Based on preclinical work, we found that combination of poly (ADP-ribose) polymerase (PARP) inhibitors with drugs that inhibit the homologous recombination repair (HRR) pathway (such as PI3K inhibitors) might sensitise HRR-proficient epithelial ovarian cancers to PARP inhibitors. We aimed to assess the safety and identify the recommended phase 2 dose of the PARP inhibitor olaparib in combination with the PI3K inhibitor alpelisib in patients with epithelial ovarian cancer and in patients with breast cancer. Methods In this multicentre, open-label, phase 1b trial following a 3 + 3 dose-escalation design, we recruited patients aged 18 years or older with the following key eligibility criteria: confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of high-grade serous histology; confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of any histology with known germline BRCA mutations; confirmed diagnosis of recurrent breast cancer of triple-negative histology; or confirmed diagnosis of recurrent breast cancer of any histology with known germline BRCA mutations. Additional patients with epithelial ovarian cancer were enrolled in a dose-expansion cohort. Four dose levels were planned: the starting dose level of alpelisib 250 mg once a day plus olaparib 100 mg twice a day (dose level 0); alpelisib 250 mg once a day plus olaparib 200 mg twice a day (dose level 1); alpelisib 300 mg once a day plus olaparib 200 mg twice a day (dose level 2); and alpelisib 200 mg once a day plus olaparib 200 mg twice a day (dose level 3). Both drugs were administered orally, in tablet formulation. The primary objective was to identify the maximum tolerated dose and the recommended phase 2 dose of the combination of alpelisib and olaparib for patients with epithelial ovarian cancer and patients with breast cancer. Analyses included all patients who received at least one dose of the study drugs. The trial is active, but closed to enrolment; follow-up for patients who completed treatment is ongoing. This trial is registered with ClinicalTrials.gov , number NCT01623349 . Findings Between Oct 3, 2014, and Dec 21, 2016, we enrolled 34 patients (28 in the dose-escalation cohort and six in the dose-expansion cohort); two in the dose-escalation cohort were ineligible at the day of scheduled study initiation. Maximum tolerated dose and recommended phase 2 dose were identified as alpelisib 200 mg once a day plus olaparib 200 mg twice a day (dose level 3). Considering all dose levels, the most common treatment-related grade 3–4 adverse events were hyperglycaemia (five [16%] of 32 patients), nausea (three [9%]), and increased alanine aminotransferase concentrations (three [9%]). No treatment-related deaths occurred. Dose-limiting toxic effects included hyperglycaemia and fever with decreased neutrophil count. Of the 28 patients with epithelial ovarian cancer, ten (36%) achieved a partial response and 14 (50%) had stable disease according to Response Evaluation Criteria in Solid Tumors 1.1. Interpretation Combining alpelisib and olaparib is feasible with no unexpected toxic effects. The observed activity provides preliminary clinical evidence of synergism between olaparib and alpelisib, particularly in epithelial ovarian cancer, and warrants further investigation. Funding Ovarian Cancer Dream Team (Stand Up To Cancer, Ovarian Cancer Research Alliance, National Ovarian Cancer Coalition), Breast Cancer Research Foundation, Novartis.

165 citations

Journal ArticleDOI
TL;DR: Avelumab exhibited promising activity in MMRD EC regardless of PD-L1 status, and IHC for MMR assessment is a useful tool for patient selection.
Abstract: PURPOSEDespite the tissue-agnostic approval of pembrolizumab in mismatch repair deficient (MMRD) solid tumors, important unanswered questions remain about the role of immune checkpoint blockade in ...

133 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: Among patients with metastatic non-small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood and, as compared with patients receiving standard care, patients received less aggressive care at the end of life but longer survival.
Abstract: Background Patients with metastatic non–small-cell lung cancer have a substantial symptom burden and may receive aggressive care at the end of life. We examined the effect of introducing palliative care early after diagnosis on patient-reported outcomes and end-of-life care among ambulatory patients with newly diagnosed disease. Methods We randomly assigned patients with newly diagnosed metastatic non–small-cell lung cancer to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. Quality of life and mood were assessed at baseline and at 12 weeks with the use of the Functional Assessment of Cancer Therapy–Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale, respectively. The primary outcome was the change in the quality of life at 12 weeks. Data on end-of-life care were collected from electronic medical records. Results Of the 151 patients who underwent randomization, 27 died by 12 weeks and 107 (86% of the remaining patients) completed assessments. Patients assigned to early palliative care had a better quality of life than did patients assigned to standard care (mean score on the FACT-L scale [in which scores range from 0 to 136, with higher scores indicating better quality of life], 98.0 vs. 91.5; P = 0.03). In addition, fewer patients in the palliative care group than in the standard care group had depressive symptoms (16% vs. 38%, P = 0.01). Despite the fact that fewer patients in the early palliative care group than in the standard care group received aggressive end-of-life care (33% vs. 54%, P = 0.05), median survival was longer among patients receiving early palliative care (11.6 months vs. 8.9 months, P = 0.02). Conclusions Among patients with metastatic non–small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival. (Funded by an American Society of Clinical Oncology Career Development Award and philanthropic gifts; ClinicalTrials.gov number, NCT01038271.)

5,450 citations

Journal ArticleDOI
TL;DR: Estimating cancer prevalence in the United States using incidence and survival data from the Surveillance, Epidemiology, and End Results cancer registries; vital statistics from the Centers for Disease Control and Prevention's National Center for Health Statistics; and population projections from the US Census Bureau is presented.
Abstract: The number of cancer survivors continues to increase in the United States because of the growth and aging of the population as well as advances in early detection and treatment. To assist the public health community in better serving these individuals, the American Cancer Society and the National Cancer Institute collaborate every 3 years to estimate cancer prevalence in the United States using incidence and survival data from the Surveillance, Epidemiology, and End Results cancer registries; vital statistics from the Centers for Disease Control and Prevention's National Center for Health Statistics; and population projections from the US Census Bureau. Current treatment patterns based on information in the National Cancer Data Base are presented for the most prevalent cancer types. Cancer-related and treatment-related short-term, long-term, and late health effects are also briefly described. More than 16.9 million Americans (8.1 million males and 8.8 million females) with a history of cancer were alive on January 1, 2019; this number is projected to reach more than 22.1 million by January 1, 2030 based on the growth and aging of the population alone. The 3 most prevalent cancers in 2019 are prostate (3,650,030), colon and rectum (776,120), and melanoma of the skin (684,470) among males, and breast (3,861,520), uterine corpus (807,860), and colon and rectum (768,650) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost two-thirds (64%) are aged 65 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by follow-up care providers. Although there are growing numbers of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care.

2,924 citations

Journal ArticleDOI
17 Mar 2017-Science
TL;DR: Current knowledge of PARP inhibitors and potential ways to maximize their clinical effectiveness are discussed, and interesting lessons for the development of other therapies are provided.
Abstract: PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair defect. PARPi also show promising activity in more common cancers that share this repair defect. However, as with other targeted therapies, resistance to PARPi arises in advanced disease. In addition, determining the optimal use of PARPi within drug combination approaches has been challenging. Nevertheless, the preclinical discovery of PARPi synthetic lethality and the route to clinical approval provide interesting lessons for the development of other therapies. Here, we discuss current knowledge of PARP inhibitors and potential ways to maximize their clinical effectiveness.

1,643 citations

Journal ArticleDOI
TL;DR: The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression‐free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olAParib than with placebo.
Abstract: Background Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the o...

1,552 citations

Journal ArticleDOI
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

1,545 citations