SUMMARY Pertuzumab is a humanized monoclonal antibody directed at the dimerization domain of the receptor tyrosine-protein kinase erbB-2 (HER2) receptor. It possesses a unique and complimentary mechanism of action compared to trastuzumab, which has historically been the cornerstone of therapy for HER2-amplified breast cancer. Clinical trials demonstrate improved outcomes, with minimal increases in toxicity with the addition of pertuzumab to trastuzumab in patients with HER2-positive metastatic breast cancer, indicating the advantage of dual HER2 receptor blockade. Pertuzumab is approved as first-line therapy in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer, with future opportunities to investigate its efficacy in other stages of breast cancer, as well as in the treatment of other malignancies.
Background: Patients face complex treatment choices with a range of benefits/risks. Researchers seek new biomarkers to predict individualized risks/benefits. It is essential that biomarkers yield information useful to patients. Our prior research in metastatic breast cancer showed choice-based conjoint (CBC) allowed patients to express risk-benefit preferences. This study focused on patients with early stage breast cancer who received chemotherapy and quantified relative influence of benefit and specific toxicities on predicted treatment choice for common therapies. Methods: A CBC survey was developed and sent to patients. The survey showed 12 pairs of hypothetical treatment choices based on benefit/risk profiles similar to those of TC, AC, AC®T, and TAC to allow assessment of what drove selections. Choices included benefit (relative risk reduction range: 20%-50%) and likelihood of toxicities including: peripheral neuropathy (PN range: 0%-60% with degrees of severity/duration); congestive heart failure (CHF range: 0%-10%); and clinically relevant infection (CRI range: 5%-25%). Analysis (N = 417) allowed treatment choice prediction for any benefit/toxicity combination. Hypothetical biomarkers were modeled to determine shifts in toxicity/efficacy necessary to change treatment selection. Results: Severity of PN experience had significant influence in decisions. When simply asking patients for perceived impact of previous PN experience on a future decision, the majority who had mild/moderate PN felt a future decision would not be impacted by a similar experience. Conversely, a plurality (47%) who had prior severe PN would be less likely to take similar future treatment. With CBC, we examined the derived influence of risks/benefits on treatment decisions. Based on estimated benefit/risk profiles, 50% selected a regimen similar to TC > AC (22%) > AC→T (16%) > TAC (10%). Incremental benefit had substantial impact on selected regimen. The desire for a given regimen decreased with incremental increase for each toxicity; most dramatically for CHF. Patients with a perception of low recurrence risk had higher preference for a non-anthracycline based profile, while those with higher perceived recurrence risk had higher preference for a combined anthracycline/taxane based profile. Interestingly, PN-naive patients had higher preference for non-taxane based profile, whereas those who had prior PN had higher preference for some taxane-based profiles. With moderate/limited PN, substantially more PN-naive patients avoided a taxane profile (31%) vs. those who had experienced PN (18%). When focusing on likelihood of severe/irreversible PN, there was dramatic shift toward non-taxane based regimens: AC (53%) > TC (23%) > AC→T (20%) > TAC (3%). When modeling impact of biomarkers on therapy selection, as likelihood of PN in taxane profiles increased, the fraction that chose a non-taxane profile increased. As likelihood of CHF in anthracycline-based profile increased, the fraction that chose such a regimen decreased. Conclusion: Patients considered all information about benefit and risks when making treatment choices. The information effective hypothetical biomarkers could add impacted these choices. Personal experience with a given toxicity appeared to impact decision for future therapies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-08-05.
Population-based studies have suggested improved survival for patients diagnosed with MBC in recent years, presumably due to the availability of new and more effective therapies (Chia et al. Cancer 2007; Dawood et al. JCO, 2008). The objective of this analysis was to determine if survival improved for patients who participated in Eastern Cooperative Oncology Group (ECOG) adjuvant trials and later developed MBC. Methods: Adjuvant trials coordinated by the ECOG that accrued patients between 1978 and 2002 were reviewed (n=12), which included followup until 2010. Cytotoxic and biologic agents approved for MBC during this time included paclitaxel (1994), capecitabine and trastuzumab (1998), docetaxel and gemcitabine (2004), lapatinib and ixabepilone (2007), and bevacizumab (2008). Survival following distant recurrence was estimated for 4 time periods ranging from 6–10 years, and adjusted for baseline covariates in a Cox proportional hazards model. Because distant relapse free interval (DRFI) was the covariate most strongly associated with survival after recurrence, and the potential for “gap time” bias this could introduce, logrank tests for other covariates and estimates of effects were computed stratified on DRFI (0-3, >3-6, > 6 years). HER2 status was not routinely available and thus not included. Results: The 12 trials included 14,752 patients (93% received adjuvant chemotherapy); 3711 (25.2%) developed distant recurrence. Median survival after distant recurrence was 20 months; the estimated 5 and 10-year survival rates were 16.3% and 6.1%, respectively. Median survival by time period is shown in the table, stratified by DRFI. Median survival did not significantly change over time by DRFI (≤3 years, p=0.15; >3 yr, p=0.57). In a Cox proportional hazards model, factors associated with inferior survival after adjusting for other covariates included shorter DRFI (<3 years vs. 3–6 years — hazard ratio [HR] 1.60, p<0.001, and > 6 vs. < 3 years — HR 2.23, p <0.001), ER-negative disease (HR 1.30, p<0.001), PR-negative disease (HR 1.36, P<0.0001), number of positive axillary nodes at diagnosis (1-3 vs. 0 nodes — HR 1.28, 4–9 vs. 0 nodes — HR 1.51, > 9 vs. 0 nodes — HR 1.51, p<0.0001), and black vs. white race (HR 1.29, p=0.0003), but not age at recurrence (p=0.07). When the year of recurrence was added to the Cox proportional hazards model using the intervals shown in the table below, it was not significantly associated with survival. Results were similar when 1978–2010 was assessed by 5–6 year intervals. Conclusions: In contrast to reports from population-based studies, we do not observe any improvement in survival over time for patients who develop distant recurrence after adjuvant chemotherapy. There remains a critical unmet need for new therapies for MBC, especially for those who recur after adjuvant chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-01.
Background Those living with metastatic breast cancer (MBC) have distinct and shifting concerns in regard to education and decision making in considering clinical trials as a treatment option. Clinical trials designs, are becoming increasingly complex, and many patients have concerns for biomarker requirements Aims/Research Questions · What is the status of MBCA advocacy members' and partners' digital information, education and access to metastatic breast cancer trials? · What plans do MBCA members/partners have for the next 6-18 months to educate and inform their constituents for the 2018 rollout of BreastCancerTrials.org's (BCT)Metastatic Trial Search (MTS) and Metastatic Trial Talk (MTT) and other trial matching systems? · What are the top 5 barriers regarding trial enrollment? · What are best practices for MBC trial education? Research Methodology and Design A comprehensive analysis was conducted comprising both secondary and primary research to inform these specific aims. Secondary research was conducted using previous capture of MBCA online digital resources and strengthened to include additional research on MBCA members and partners online resources including pages specifically devoted to clinical trials and metastatic clinical trials. Mixed methods approaches include: 1) An assessment of MBCA members' and partners' digital media presence regarding MBC trials using a standardized form and rating system, and an analysis of MBCA members 2017 use of MTS using BCT secondary data; 2) Structured, recorded interviews with selected MBCA members/ partners, sharing the results of the assessments and querying them regarding their future plans and perceived barriers; and 3) Mixed methods analyses of the interview recordings using DeDoose to assess and articulate key trends and perceptions. Statistical Methods Simple frequency percentages and means were used in the assessment rankings of the MBCA members. DeDoose was used to provide mixed method analyses of the MBCA member and partner interviews. Results Analysis of the MBCA members and partners websites and digital media showed that, increasingly, both groups use the full variety of digital media to educate their constituents regarding MBC clinical trials. The 13 MBCA advocacy members providing online access to BreastCancerTrials' MTS in 2017 provided 97% of the traffic to the MTS trial matching service. System types accessing the MTS widget were 57.3% desktops, 28.6% mobile devices and 14% tablets. Table 1 shows assessment totals of 5 categories of the 13 MBCA advocacy group members' websites using MTS as compared to the 19 MBCA members not using the widget. Table 2 shows the 2017 usage of BCT's MTS with 97% of the page views coming from MBCA members. Table 1.Assessment Ratings of MBCA Advocacy Partners on Metastatic Trial Education/AccessAwareness of Trials (e.g. explains trial Phases)Knowledge SharingInterest in Metastatic Breast CancerAction Potential for clinical trial access or enrollmentTotal (0-100)13 MBCA Advocate Members with MTS widget22.1523.0024.3124.1593.6219 MBCA Members without MTS widget13.2113.9513.5311.9552.16 Table 2.2017 Use Of Metastatic Trial SearchBCT's Metastatic Trial Search (MTS) Results2017Annual Page views33,360Unique Sessions14,295Show Trials8,100Show Trials by month675Average Time on Site (minutes)3:34Total Engagement Events5,006 Citation Format: Vollmer Dahlke DJ, Smith ML, Han G, Ory MG, Cohen E. Metastatic breast cancer alliance's patient education and access to trials: Perceptions and actions [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-14-03.
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