Investigator

Shitanshu Uppal

University Of Michigan

SUShitanshu Uppal
Papers(2)
Physician Influence o…Phase I trial of ribo…
Collaborators(6)
Karen McLeanKent GriffithLauren P. WallnerMegan A. MullinsPhilippa ClarkeRonald J. Buckanovich
Institutions(4)
University Of MichiganRoswell Park Comprehe…U M Rogel Cancer Cent…University of Pittsbu…

Papers

Physician Influence on Variation in Receipt of Aggressive End-of-Life Care Among Women Dying of Ovarian Cancer

PURPOSE: End-of-life care for women with ovarian cancer is persistently aggressive, but factors associated with overuse are not well understood. We evaluated physician-level variation in receipt of aggressive end-of-life care and examined physician-level factors contributing to this variation in the SEER-Medicare data set. METHODS: Medicare beneficiaries with ovarian cancer who died between 2000 and 2016 were included if they were diagnosed after age 66 years, had complete Medicare coverage between diagnosis and death, and had outpatient physician evaluation and management for their ovarian cancer. Using multilevel logistic regression, we examined physician variation in no hospice enrollment, late hospice enrollment (≤ 3 days), > 1 emergency department visit, an intensive care unit stay, terminal hospitalization, > 1 hospitalization, receiving a life-extending or invasive procedure, and chemotherapy (in the last 2 weeks). RESULTS: In this sample of 6,288 women, 51% of women received at least one form of aggressive end-of-life care. Most common were no hospice enrollment (28.9%), an intensive care unit stay (18.6%), and receipt of an invasive procedure (20.7%). For not enrolling in hospice, 9.9% of variation was accounted for by physician clustering ( P < .01). Chemotherapy had the highest physician variation (12.4%), with no meaningful portion of the variation explained by physician specialty, volume, region, or patient characteristics. CONCLUSION: In this study, a meaningful amount of variation in aggressive end-of-life care among women dying of ovarian cancer was at the physician level, suggesting that efforts to improve the quality of this care should include interventions aimed at physician practices and decision making in end-of-life care.

Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer

BACKGROUNDNew therapeutic combinations to improve outcomes of patients with ovarian cancer are clearly needed. Preclinical studies with ribociclib (LEE-011), a CDK4/6 cell cycle checkpoint inhibitor, demonstrate a synergistic effect with platinum chemotherapy and efficacy as a maintenance therapy after chemotherapy. We tested the safety and initial efficacy of ribociclib in combination with platinum-based chemotherapy in recurrent ovarian cancer.METHODSThis phase I trial combined weekly carboplatin and paclitaxel chemotherapy with ribociclib, followed by ribociclib maintenance in patients with recurrent platinum-sensitive ovarian cancer. Primary objectives were safety and maximum tolerated dose (MTD) of ribociclib when given with platinum and taxane chemotherapy. Secondary endpoints were response rate (RR) and progression-free survival (PFS).RESULTSThirty-five patients were enrolled. Patients had a mean of 2.5 prior lines of chemotherapy, and 51% received prior maintenance therapy with poly(ADP-ribose) polymerase inhibitors and/or bevacizumab. The MTD was 400 mg. The most common adverse events included anemia (82.9%), neutropenia (82.9%), fatigue (82.9%), and nausea (77.1%). The overall RR was 79.3%, with a stable disease rate of 18%, resulting in a clinical benefit rate of 96.6%. Median PFS was 11.4 months. RR and PFS did not differ based on the number of lines of prior chemotherapy or prior maintenance therapy.CONCLUSIONThis work demonstrates that the combination of ribociclib with chemotherapy in ovarian cancer is feasible and safe. With a clinical benefit rate of 97%, this work provides encouraging evidence of clinical efficacy in patients with recurrent platinum-sensitive disease.TRIAL REGISTRATIONClinicalTrials.gov NCT03056833.FUNDINGThis investigator-initiated trial was supported by Novartis, which provided drugs and funds for trial execution.

2Papers
6Collaborators
1Trials