Hurria, Arti

Abstract Background: In CALGB-49907 (NEJM 2009;360:2055), older patients (pts) with ESBC were randomized to standard adjuvant chemo (AC or CMF versus capecitabine). The objective of this secondary QoL analysis is to assess if pts’ BL chemo preference (CP, defined as high or low), is associated with the following during and after completion of chemo: self and professional-reported toxicity, changes in mental health, function, QoL, recurrence-free (RFS) and overall (OS) survival. Patients and Methods: Of 633 trial pts 350 participated in the QoL substudy; 145/350 pts completed the BL assessment regarding CP. CP was measured by asking the amount of benefit women would require to choose adjuvant chemo in a hypothetical situation, irrespective of chemo agents. Women who chose chemo for an increase in OS of ≤12 months (mo) were designated as high chemo preference (HCP) and those who chose >12 mo were designated low chemo preference (LCP). CP associations were evaluated with: BL perception of self-health and perceived QoL on chemo; patient reported outcomes (PROs), changes in function and QoL (based on EORTC-QLQ-C30); anxiety and depression (Hospital Anxiety and Depression Scale); observed grade 3-5 adverse events (AEs) by NCI common toxicity criteria (CTC v2.0). Pts were assessed at midtreatment and at 1, 12, 18 and 24 mo post-treatment. Chi-square tests, t-tests, and Cox models were used for categorical, continuous, and time-to-event variables, respectively. Results: The demographic and tumor characteristics of women (median age 71) who provided CP at BL were not different from women in the QoL subset or from non-QoL pts. 68/145 (47%) women had a HCP. CP groups did not differ based on age, surgery type, tumor and nodal stage, hormone receptor status, performance status, chemo assignment, education, marital or employment status except the LCP group had a higher proportion of white women (95% vs. 78%, p=0.004). At BL, there were no differences in perception of self-health based on CP but women with LCP predicted QoL on chemo to be worse than women with HCP (p=0.006) and reported greater nausea/vomiting. Mid-treatment, LCP pts reported worse nausea/vomiting, financial worries, and cancer symptoms. Post-treatment, LCP pts had worse constipation (at 1 mo) and financial worries (at 24 mo). There were no differences based on CP for dyspnea, pain, fatigue, insomnia, anxiety or depression at any timepoint. Mid-treatment, LCP women reported lower QoL and worse social, emotional and physical function compared to HCP women. These scores were not significantly different after treatment completion. LCP women had significantly higher rates of grade 3-5 AEs (53 vs. 34%, p=0.02) during treatment but these did not persist post-therapy. CP was not significantly associated with OS (HR =0.75, p=0.36) or RFS (HR=0.94, p=0.84). Conclusions: LCP at BL was associated with lower QoL, worse physical symptoms, AEs and function mid-therapy, but not mental health. Mid-therapy declines in women with LCP largely reversed post-therapy. This information may be useful for oncology professionals to counsel older ESBC pts with LCP receiving adjuvant chemo. Citation Format: Ajeet Gajra, Linda McCall, Hyman B Muss, Harvey J Cohen, Aminah Jatoi, Karla V Ballman, Ann H Partridge, Linda Sutton, Barbara A Parker, Gustav Magrinat, Jaqueline M Lafky, Arti Hurria. Association of patient preference for adjuvant chemotherapy (chemo) at baseline (BL) with toxicity, mental health, function, quality of life (QoL) and survival in older women with early stage breast cancer (ESBC) [CALGB 49907 Alliance] [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-07.

Comorbidity was associated with shorter overall survival but not toxicity or relapse among older women with breast cancer with good functional status.

Abstract Background: The potential for exploiting BRCA deficiencies with DNA repair inhibitors has both pre-clinical and clinical support. ABT-888 (veliparib), a DNA repair inhibitor initially thought to target Poly(ADP-Ribose) Polymerases (PARP), has demonstrated in vitro inhibition of BRCA1 and BRCA2 deficient mouse embryonic stell cells, with a larger effect on BRCA1 cells. We report on the pre-planned interim analysis of the efficacy of single agent veliparib in patients with either BRCA1 or BRCA2-associated stage IV breast cancer. Methods: BRCA 1 or 2 carrier patients with stage IV breast cancer, with measurable disease, without prior exposure to a PARP inhibitor or a platinum compound in the metastatic setting, were eligible. Velapirib was administered orally, at doses of 400 mg twice daily. Dose adjustments based on toxicity were permitted. Patients progressing on velapirib alone received carboplatin at an AUC of 5, IV, given Q 21 days, and velapirib 150 mg twice daily (the maximum tolerated dose [MTD] of the combination from our completed Phase I study: J Clin Oncol 30, 2012 [suppl; abstr 1024]). Patients were to be accrued from 7 NCI NO1- supported consortia. Initially 10 patients were to be accrued to each stratum (BRCA1 and BRCA2) to provide evidence of single agent activity. If there was sufficient activity to warrant consideration of velapirib as single agent therapy (defined as 2 or more confirmed partial [PR] or better responses out of 10 per stratum), an additional 12 patients would be accrued per stratum. Results: 20 evaluable patients (11 BRCA1 and 9 BRCA2 [1 in screening]) have been accrued, the majority with lung or liver as visceral metastatic sites of disease. Median age (range) is 46 (29-68) years. Tumors from 9 patients were hormone receptor positive. BRCA1 cohort: 4 of 11 patients are off treatment at a median of 2 months (1-4); 1 patient stopped velapirib due to toxicity (grade 2 rash/pruritus, grade 2 vomiting), 3 stopped for progressive disease (one with an unconfirmed PR). Seven patients are still on single agent veliparib with 1 unconfirmed PR, and 1 patient with two evaluations showing stable disease. BRCA2 cohort: 2 patients are off treatment at 2 months for progressive disease, 7 are still on treatment with 1 confirmed PR, and 3 unconfirmed PRs. Data on patients receiving combination of velapirib and carboplatin after progression is too early. Treatment-related toxicity is being updated and has so far been reported from 14 patients: 1 patient had grade 3 fatigue, 1 patient with liver metastasis had both grade 3 alanine aminotransferase elevation and grade 3 abdominal pain. Grade 2 toxicities occurring in more than 1 patient included nausea/vomiting (6 patients), chills (2 patients), and fatigue (2 patients). Conclusion: Velapirib has single agent activity in both BRCA1 and BRCA2-associated stage IV breast cancer patients, and is well-tolerated. Mature response, treatment, and toxicity data will be presented. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-05.

A majority of cancer diagnoses and deaths occur in patients age ≥ 65 years. With the aging of the US population, the number of older adults with cancer will grow. Although the coming wave of older patients with cancer was anticipated in the early 1980s, when the need for more research on the cancer-aging interface was recognized, many knowledge gaps remain when it comes to treating older and/or frailer patients with cancer. Relatively little is known about the best way to balance the risks and benefits of existing cancer therapies in older patients; however, these patients continue to be underrepresented in clinical trials. Furthermore, the available clinical trials often do not include end points pertinent to the older adult population, such as preservation of function, cognition, and independence. As part of its ongoing effort to advance research in the field of geriatric oncology, the Cancer and Aging Research Group held a conference in November 2012 in collaboration with the National Cancer Institute, the National Institute on Aging, and the Alliance for Clinical Trials in Oncology. The goal was to develop recommendations and establish research guidelines for the design and implementation of therapeutic clinical trials for older and/or frail adults. The conference sought to identify knowledge gaps in cancer clinical trials for older adults and propose clinical trial designs to fill these gaps. The ultimate goal of this conference series is to develop research that will lead to evidence-based care for older and/or frail adults with cancer.