Debjani Grenier

Promoting consultation recording practice in oncology: identification of critical implementation factors and determination of patient benefit.

The objectives of this implementation study were to (i) address the evidentiary, contextual, and facilitative mechanisms that serve to retard or promote the transfer and uptake of consultation recording use in oncology practice and (ii) follow patients during the first few days following receipt of the consultation recording to document, from the patients perspective, the benefits realized from listening to the recording.

Clinical predictors of benefit from fulvestrant in advanced breast cancer: A Meta-analysis of randomized controlled trials

BACKGROUND Data on the comparative efficacy of fulvestrant and other endocrine treatments are inconsistent. Clinical markers predictive of greater benefit from fulvestrant compared to the alternate endocrine agents have not been identified. METHODS We searched the literature from inception to May 2015, using MEDLINE, EMBASE, and major conference proceedings. We included randomized controlled trials (RCTs) that compared fulvestrant containing arm to either tamoxifen or an aromatase inhibitors (AI) and presented results for subgroup analyses as Hazard Ratios (HR) for Time to Progression (TTP) or Progression Free Survival (PFS). Subgroup analyses reported in at least two RCTs were included. Data were then weighted using generic inverse variance approach and pooled in meta-analysis using RevMan 5.3 software. Difference between sub-groups was tested with chi(2) statistics. RESULTS Analysis included 4 RCTs comparing fulvestrant-based therapy to AI alone and comprising 2382 patients (1190 on fulvestrant and 1192 on control arms). TTP/PFS was the primary endpoint in all included studies. Four sub-groups fulfilled our criteria. Fulvestrant was associated with greater benefit in patients with visceral metastasis (HR 0.85 vs 1.02 for no visceral disease, p for difference=0.05) and in those patients with a time to recurrence >5 years (HR 0.80 vs 1.09 for recurrence ⩽5 years, p for difference=0.02). There was no apparent difference in benefit based on age >65 years (HR 0.86 vs 0.96, p for difference=0.32) or HER2/neu status (HR 0.36 vs 0.92, p for difference=0.09). CONCLUSION Patients with advanced breast cancer with visceral involvement and longer time from diagnosis to recurrence had significantly better TTP/PFS with the use of fulvestrant. These results may have implications for selection of patients in the design of future clinical trials and to inform treatment decisions in clinical practice.

Abstract P5-14-02: Clinical predictors of benefit from fulvestrant in advanced breast cancer: A meta-analysis of randomized controlled trials

Background: While fulvestrant is approved by the United Stated Food and Drug Administration as an alternate endocrine therapy for treatment of advanced breast cancer, data on its efficacy compared to other endocrine treatments are inconsistent. Clinical markers predictive of greater benefit from fulvestrant compared to the alternate endocrine agents have not been identified. Methods: We searched the literature from inception to May, 2015 from MEDLINE, EMBASE, and major conference proceedings. We included randomized controlled trials that evaluated Fulvestrant compared to either tamoxifen or an AI. We collected the efficacy data reported as Time to Progression (TTP) or Progression Free Survival (PFS) on 7 distinct subgroup of patients from the RCTs defined by: age, time to cancer reoccurrence from primary diagnosis, presence of visceral metastasis, previous chemotherapy exposure, presence of measurable disease, hormone receptor status and, HER-2 status. Data on rates of occurrences of 9 most frequently reported adverse events were also collected from both arms of the studies. Data on both efficacy and toxicity were then weighted using generic inverse variance approach and pooled in a meta-analysis using RevMan 5.3 software. Results: We identified 8 RCTs that fulfilled our criteria and involved 4,024 patients (2,032 on fulvestrant and 1,992 on control arms). TTP/PFS was the primary endpoint in 7 out of 8 RCTs and secondary endpoint in one. Compared to an AI or tamoxifen, there was a statistically significant improvement in TTP favoring fulvestrant in patients who had visceral metastasis [Hazards Ratio (HR) 0.86; 95% Confidence Interval (CI) 0.77 to 0.96, pl0.01], measurable disease [HR 0.74; 95% CI 0.58 to 0.93, p=0.01], and HER-2 overexpression [HR 0.43; 95% CI 0.27 to 0.70, pl0.001]. Similar effect sizes were observed in a sensitivity analysis excluding the trials of combinations of fulvestrant and AI in the experimental arm. Rates of occurrences of adverse events were similar between fulvestrant and other endocrine agents. Conclusion: Patients with advanced breast cancer that have visceral disease, measurable disease, or HER-2 driven disease are likely to derive higher benefits from treatment with fulvestrant compared to tamoxifen or an AI. These results may have implications for selection of patients in the design of future clinical trials and to inform treatment decisions in clinical practice. Citation Format: Niraula S, Pitz M, Gordon V, Grenier D, Amir E, Brandes L. Clinical predictors of benefit from fulvestrant in advanced breast cancer: A meta-analysis of randomized controlled trials. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-14-02.

Abstract P3-07-13: Outcomes of women with small, early-stage breast cancer in Manitoba from 1995-2011

OBJECTIVES: The objectives of this study were to describe the distribution, management, and outcomes of women with early-stage breast cancer in Manitoba during the period from 1995-2011. Specifically, we looked at tumours 1cm or smaller in size (T1mic/T1a/T1b) across the spectrum of molecular phenotypes: estrogen-receptor (ER) status, progesterone-receptor (PR) status, and human epidermal growth factor receptor 2 (HER2) status. This is the first study to evaluate these objectives in Manitoba, and will contribute significantly to the limited data of long-term outcomes for smaller-sized breast tumours. METHODS: Using the Manitoba Cancer Registry, we created a retrospective cohort of all patients with primary breast cancer of 1.0 cm or less, between 1995 and 2011. Women with previous or synchronous contralateral breast cancers were excluded. Data included patient demographics, diagnostic procedure, tumour size, nodal disease, treatment modalities (surgery, radiotherapy, hormone therapy, and chemotherapy), ER status, PR status, and HER2 status. Linkage to the Manitoba Health Drug Program Information Network (DPIN) database allowed capture of all hormonal therapies. Patient outcomes were evaluated, including risk of recurrence, overall survival and relative survival. Risk of recurrence was illustrated using cumulative incidence of recurrence, accounting for the competing risk of death. Kaplan-Meier curves were used to illustrate overall survival. The relative survival estimate was used to estimate the probability of surviving from breast cancer while controlling for differences in mortality due to other causes. RESULTS: Our study captured 2,341 women. Mean age at diagnosis was 62. ER+, PR+, and HER2+ status were 71% (11% unknown), 61.6% (11% unknown), and 8.6% (31% unknown), respectively. Clinically, 78% were Stage I disease, and by tumour size overall: T1mic 11.5%, T1a 18.9%, and T1b 69.7%. Ninety-eight percent had primary surgery, 58% had primary radiation, 48% received hormone therapy, and 16% received chemotherapy. At last follow-up, 21% of all patients were deceased. Relative survival estimates revealed that the survival of the overall cohort was not different than the general population, when comparing based on age groupings for Manitoban females. Recurrence occurred in 6.6% (156) of all cases. ER+, PR+, and HER2+ status were 63% (4% unknown), 58% (4% unknown), and 48% (5% unknown), respectively. By staging, 65% were Stage I disease and by tumour size 60% were T1b. Overall, 64% of recurrences were node-negative. For the HER2+, node-negative subpopulation at diagnosis: 21% of the T1mic group recurred, 41% of T1a recurred, and 19% of T1b recurred. In all recurrences, 39% of patients were deceased at last follow-up. CONCLUSIONS: Small, early-stage breast cancers are common and a significant proportion of patients recur. HER2-positivity appears to be an important risk factor for recurrence and may independently warrant treatment with trastuzumab, regardless of primary tumour size. Citation Format: Aly-Khan Lalani, Katherine Fradette, Rashid Ahmed, Debjani Grenier, Marshall Pitz. Outcomes of women with small, early-stage breast cancer in Manitoba from 1995-2011 [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 P3-07-13.

Promoting consultation recording practice in oncology: Identification of critical implementation factors and determination of patient benefit.

155 Background: The objectives of this implementation study were to 1) identify and address the evidentiary, contextual, and facilitative mechanisms that serve to retard or promote the transfer and uptake of consultation recording use in oncology practice, and 2) follow patients during the first few days following receipt of the consultation recording to document, from the patients perspective, the benefits realized from listening to the recording. METHODS Nine medical and 9 radiation oncologists from cancer centers in three Canadian cities (Calgary, Vancouver, Winnipeg) recorded their primary treatment consultations for 228 patients newly diagnosed with prostate or breast cancer. The Digital Recording Use Semi-Structured Interview (DRUSSI) was conducted at two days post-consultation and at 1-week post-consultation. Each oncologist was given a feedback letter summarizing the consultation recording benefits reported by their patients. RESULTS Sixty-nine percent of patients listened to at least a portion of the recording within the first week following the consultation. Consultation recording favourableness ratings were high: 93.6% rated the intervention between 75-100 on a 100-point scale. Four main areas of benefit were reported: 1) Anxiety reduction; 2) Enhanced retention of information; 3) Better informed decision making; and 4) Improved communication with family members. Eight fundamental components of successful transfer and uptake of consultation recording practice were identified. CONCLUSIONS Implementation research and additional randomized trials are needed to facilitate the transfer and uptake of consultation recording use so that far more patients and significant others may realize the associated benefits.