ASCO's approach to a learning health care system in oncology.
Journal of oncology practice / American Society of Clinical Oncology
2013; 9 (3): 145-148
CancerLinQ and the Future of Cancer Care.
American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting
2013; 2013: 430-434
The promise of emerging science and the challenges confronting today's health care system can both be addressed by fully embracing the IoM's vision of a learning health care system. ASCO's initial foray into realizing this vision for oncology shows great promise.
View details for DOI 10.1200/JOP.2013.000957
View details for PubMedID 23942494
A randomized trial of combination anastrozole plus gefitinib and of combination fulvestrant plus gefitinib in the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer
BREAST CANCER RESEARCH AND TREATMENT
2012; 133 (3): 1049-1056
Patients, health care providers, and payers all have a similar interest in a health care system that is both efficient and intelligent. The attributes of such a system are widely recognized: we want a system that provides widespread access to consistently high-quality, science-based medical care; we want that system to be efficient, avoiding unnecessary waste, while delivering the right treatments to the right patients in a timely fashion; we want a system that allows us to both learn from our experience and generate new knowledge that will inform future treatment options; and we want a system that is compassionate and caring. What we want from a health care system often runs up against real-life obstacles and challenges: a fragmented delivery system, varying levels (or lack of) insurance, a growing burden of regulation and paperwork, and an increasingly complex understanding of tumor biology and the therapeutic approaches derived from this biology. New challenges are on the horizon-emerging genomic and imaging technology, with their enormous cognitive and data burdens, and a looming demographic challenge, where inadequate personnel resources face an aging population and an explosion of new treatments. Not all problems have technologic solutions, but many of the issues described above have potential solutions related to information technology. ASCO's CancerLinQ, described in this article, is an evolving attempt by the Society to improve the quality and efficiency of cancer care, while supporting education and research in the cancer field.
View details for DOI E10.1200/EdBook_AM.2013.33.430
View details for PubMedID 23714566
Poly(ADP-Ribose) Polymerase Inhibition: "Targeted" Therapy for Triple-Negative Breast Cancer
CLINICAL CANCER RESEARCH
2010; 16 (19): 4702-4710
EGFR signalling pathways appear involved in endocrine therapy resistance in breast cancer. This trial estimates the antitumor efficacy and toxicity of the EGFR tyrosine kinase inhibitor gefitinib in combination with anastrozole or fulvestrant in postmenopausal hormone receptor positive breast cancer. Subjects with estrogen receptor and/or PgR positive, metastatic breast cancer were randomized into this phase II study of gefitinib (initial dose was 500 mg orally daily, due to high rate of diarrhea, starting dose was reduced to 250 mg orally daily) with either anastrozole 1 mg daily or fulvestrant 250 mg every 4 weeks. The primary endpoint was clinical benefit (complete responses plus partial responses plus stable disease for 6 months or longer). 141 eligible subjects were enrolled, 72 in the anastrozole plus gefitinib arm, and 69 in the fulvestrant plus gefitinib arm. Anastrozole plus gefitinib had a clinical benefit rate of 44% [95% confidence interval (CI) 33-57%] and fulvestrant plus gefitinib 41% (95% CI 29-53%). Median progression-free survival was 5.3 months (95% CI 3.1-10.4) versus 5.2 months (95% CI 2.9-8.2) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. Median survival was 30.3 months (95% CI 21.2-38.9+) versus 23.9 months (95% CI 15.4-33.5) for anastrozole plus gefitinib versus fulvestrant plus gefitinib, respectively. In general, the toxicity is greater than expected for single agent endocrine therapy alone. Anastrozole plus gefitinib and fulvestrant plus gefitinib have similar clinical benefit rates in the treatment of estrogen and/or PgR positive metastatic breast cancer, and the rates of response are not clearly superior to gefitinib or endocrine therapy alone. Further studies of EGFR inhibition plus endocrine therapy do not appear warranted, but if performed should include attempts to identify biomarkers predictive of antitumor activity.
View details for DOI 10.1007/s10549-012-1997-5
View details for Web of Science ID 000305914900022
View details for PubMedID 22418699
In contrast to endocrine-sensitive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, novel agents capable of treating advanced triple-negative breast cancer (TNBC) are lacking. Poly(ADP-ribose) polymerase (PARP) inhibitors are emerging as one of the most promising "targeted" therapeutics to treat TNBC, with the intended "target" being DNA repair. PARPs are a family of enzymes involved in multiple cellular processes, including DNA repair. TNBC shares multiple clinico-pathologic features with BRCA-mutated breast cancers, which harbor dysfunctional DNA repair mechanisms. Investigators hypothesized that PARP inhibition, in conjunction with the loss of DNA repair via BRCA-dependent mechanisms, would result in synthetic lethality and augmented cell death. This hypothesis has borne out in both preclinical models and in clinical trials testing PARP inhibitors in both BRCA-deficient and triple-negative breast cancer. The focus of this review includes an overview of the preclinical rationale for evaluating PARP inhibitors in TNBC, the presumed mechanism of action of this novel therapeutic class, promising results from several influential clinical trials of PARP inhibition in advanced breast cancer (both TNBC and BRCA deficient), proposed mechanisms of acquired resistance to PARP inhibitors, and, finally, concludes with current challenges and future directions for the development of PARP inhibitors in the treatment of breast cancer.
View details for DOI 10.1158/1078-0432.CCR-10-0939
View details for Web of Science ID 000282647900004
View details for PubMedID 20858840