Jacques Raphael

The Impact of Angelina Jolie (AJ)’s Story on Genetic Referral and Testing at an Academic Cancer Centre in Canada

In May 2013, Angelina Jolie revealed to the media that she had undergone preventive double mastectomy after testing positive for a BRCA1 gene mutation. Media coverage has been extensive, but it is not clear how such a personal story affected the public and cancer genetics clinics. We conducted a retrospective review using data from the clinical database of the Familial Cancer Program at our centre. The impact of Ms. Jolie’s story on genetic counseling referrals and the appropriateness of such referrals were assessed and reported. The number of women referred for genetic counseling increased by 90xa0% after 6xa0months and remained high one year after AJ’s story with an increase of 88xa0% from baseline. The number of women who qualified for genetic testing increased by 105xa0% after 6xa0months; this increase persisted but was somewhat lower after one year with an increase of 68xa0% from baseline. Furthermore the number of BRCA1/2 carriers identified increased by 110xa0% after 6xa0months and by 42xa0% after one year.The effect of Mrs. Jolie’s story persisted one year after its release; however in the latter half of the year, the hereditary cancer risk of referred women was significantly lower than initially observed. The next challenge for our health care system will not only be to meet the increased demand for cancer genetic services in our region, but also to ensure that referrals and hence use of genetic counseling resources are appropriate.

Overall survival (OS) endpoint: an incomplete evaluation of metastatic breast cancer (MBC) treatment outcome

Overall survival (OS) has been debated as the most important clinical endpoint in metastatic breast cancer (MBC) trials mainly because survival could be influenced by treatment after progression in an era of effective subsequent-line agents. We conducted a search strategy using PubMed for all the phase 3 trials in the last two decades evaluating survival outcome in MBC. We investigated the frequency of trials reporting survival outcome and response/resistance to treatment beyond progression. One hundred fifteen trials met our eligibility criteria: 69 (60xa0%) evaluated chemotherapy regimens (group A), 32 (28xa0%) evaluated targeted therapies (group B), and 14 (12xa0%) focused on endocrine treatment (group C). An OS benefit was demonstrated in approximately 22xa0% of the trials in each group. Less than 10xa0% of the trials in group A and B reported response data after progression on trial therapy. Post-progression treatment resistance was only reported in group A in 3xa0% (2/69) of the trials. In addition, the number of lines of treatment used post-progression was reported in 14xa0% (10/69), 9.4xa0% (3/32), and 14xa0% (2/14) of the trials in group A, B, and C, respectively. Post-progression survival and its effect on OS was reported in only 1xa0% (1/69), 3xa0% (1/32), and 7xa0% (1/14) of the trials for group A, B, and C respectively. A clear paucity of post-progression treatment information is noted in the majority of the phase 3 trials for MBC. We do know that OS can be affected partially or directly by treatments used after progression. In order to assess the true clinical benefit of a new drug and to have a complete evaluation of OS outcome, a detailed collection of post-progression treatment information is required and should be mandated in MBC trials.

The impact of Angelina Jolie's (AJ) story on genetic referral and testing at an academic cancer centre.

44 Background: In May 2013, AJ revealed to the media that she had undergone preventive double mastectomy. The actress had a family history of breast and ovarian cancer and tested positive for the BRCA1 gene mutation. Media coverage has been extensive, but its not clear what messages the public and professional medical staff took from this personal story that sometimes could be misleading.nnnMETHODSnWe conducted a retrospective review in our centre using data from the clinical database of the Familial Cancer Program in a tertiary care cancer centre. The impact of AJs story on genetic counseling referrals was assessed by comparing the number of referrals made 6 months before and after the story. In addition, the quality of referrals was reported by comparing the number of patients who qualified for genetic testing as defined by the Ontario Ministry of Health and Long Term Care and the ones who carried a BRCA1/2 mutation before and after the media release.nnnRESULTSnThe number of women referred for genetic counseling increased by 85% after the release of AJs story (479 before versus 887 after). This translated to an increase of 99% in the number of women who qualified for a genetic testing (211 before versus 419 after). Among them, 120 and 254 women had a history of breast and ovarian cancer in their family, 16 and 37 women had a history of male breast cancer in their family, and 28 and 15 women were diagnosed with breast cancer at the age of 35 or less before and after AJs story respectively. Furthermore, the number of BRCA1/2 carriers identified increased by 107% (29 (14 BRCA1, 15 BRCA2) before and 60 (32 BRCA1, 28 BRCA2) after).nnnCONCLUSIONSnThis study clearly shows that the number of genetic referrals doubled after AJs story. Nevertheless, the quality of referral remained the same with nearly the same percentage of patients who qualified for genetic testing and who were identified as BRCA1/2 carriers. The challenge is to meet the increased demand for cancer genetic services including screening, counseling, testing, and preventive surgery. After AJs story the current model of genetic counseling may need to be revisited.

Antiangiogenic Therapy in Advanced Non–small-cell Lung Cancer: A Meta-analysis of Phase III Randomized Trials

Abstract We conducted a meta‐analysis to evaluate the efficacy of adding any antiangiogenic therapy (AT) to the standard of care in advanced non–small‐cell lung cancer (NSCLC). The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, and Embase were searched to identify eligible trials. We included all phase III randomized trials with any line and type of treatment, histology. and AT dose. Pooled hazard ratios (HRs) for overall survival (OS) and progression‐free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated. We divided the population into 2 subgroups based on the bevacizumab dose. Data of 19,098 patients from 25 phase III trials were analyzed. Compared with the standard of care, the addition of AT did not prolong OS (HR 0.98; 95% confidence interval [CI], 0.96‐1.00; P = .1 and HR 0.97; 95% CI, 0.94‐1.00; P = .06 for groups 1 and 2, respectively). However, there was a significant improvement in PFS with the addition of AT (HR 0.85; 95% CI, 0.79‐0.91; P < .00001 and HR 0.81; 95% CI, 0.75‐0.88; P < .00001 for groups 1 and 2, respectively) and overall RR (OR 1.61; 95% CI, 1.30‐2.01; P < .0001 and OR 1.72; 95% CI, 1.39‐2.14; P < .00001 for groups 1 and 2, respectively). This is the first meta‐analysis including only all phase III trials with AT in NSCLC showing no significant effect on OS and an improvement in PFS and RR only. The role of AT in advanced NSCLC is still questionable; strong validated biomarkers are eagerly needed to predict which subgroup might benefit the most from such therapy.

Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis

INTRODUCTIONnThe addition of palbociclib to letrozole improves progression-free survival in the first-line treatment of hormone receptor positive advanced breast cancer (ABC). This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective.nnnMETHODSnA probabilistic discrete event simulation (DES) model was developed and parameterised with data from the PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated. A time horizon of 15 years was used in the base case with costs and effectiveness discounted at 5% annually. Time-to- progression and time-to-death were derived from a Weibull and exponential distribution. Expected costs were based on Ontario fees and other sources. Probabilistic sensitivity analyses were conducted to account for parameter uncertainty.nnnRESULTSnCompared to letrozole, the addition of palbociclib provided an additional 14.7 QALM at an incremental cost of

A single-institution experience of salvage therapy for patients with early and locally advanced breast cancer who progress during neoadjuvant chemotherapy.

161,508. The resulting incremental cost-effectiveness ratio was

Phosphoinositide 3-kinase inhibitors in advanced breast cancer: A systematic review and meta-analysis

10,999/QALM gained. Assuming a willingness-to-pay (WTP) of

The role of quantitative estrogen receptor status in predicting tumor response at surgery in breast cancer patients treated with neoadjuvant chemotherapy

4167/QALM, the probability of palbociclib to be cost-effective was 0%. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of

Tumour infiltrating lymphocytes and stromal CD68 in early stage HER2 positive breast cancer

11,000/QALM gained, the probability of palbociclib to be cost-effective was 50%.nnnCONCLUSIONnThe addition of palbociclib to letrozole is unlikely to be cost-effective for the treatment of ABC from a Canadian healthcare perspective with its current price. While ABC patients derive a meaningful clinical benefit from palbociclib, considerations should be given to increase the WTP threshold and reduce the drug pricing, to render this strategy more affordable.

Sunitinib dose-escalation after disease progression in metastatic renal cell carcinoma

PurposeProgression during neoadjuvant chemotherapy (NAT) for early and locally advanced breast cancer is generally uncommon. However, these patients tend to do poorly, and salvage therapy (ST) use is variable and often not well defined. We aimed to establish the characteristics and outcomes of breast cancer (BC) patients progressing on NAT, report the patterns of institutional ST usage, and identify predictors of ST failure.MethodsA retrospective review was conducted using the “Biomatrix” institutional database. Fisher’s exact test was used to study the association between baseline characteristics and progression after ST. Survival outcomes were estimated using Kaplan–Meier. Disease-Free Survival 1 (DFS1) and DFS2 represent the time between diagnosis and first progression, and the first and second progression, respectively. The log-rank test was used to compare survival outcomes between different ST types.ResultsThirty patients out of 413 (7.2%) progressed on primary NAT, with a median follow-up of 28.52xa0months (13.77–46.97) and a mean age of 57xa0years (standard deviation: 12). The two most frequently used ST modalities were surgery (43%) and radiation with concurrent cisplatin chemotherapy (CT/RT) (40%). Eighty percent of the patients made it to subsequent surgery and among those, 11 (69%) were initially not operable and their tumors were rendered surgically removable after ST. The initial tumor stage and grade, and the presence of lymphovascular invasion predicted progression after ST (pxa0=xa00.02, pxa0=xa00.03 and pxa0=xa00.01, respectively). Median DFS1, DFS2, and overall survival were 4.4xa0months (95% CI 3.6–5.7), 14.8xa0months (95% CI 2.37–NR), and 39.5xa0months (95% CI 22.73–NR), respectively. No difference in survival outcomes based on ST type was seen.ConclusionIn this evaluated cohort and despite potential poorer outcomes, patients progressing on NAT responded well to ST, became operable, and had promising survival outcomes. Appropriate selection of ST is crucial, and can help improve outcomes in such patients.