Despite evidence from clinical trials showing the efficacy of shorter durations of therapy, most HER2-positive early breast cancer (EBC) patients receive a year of anti-HER2 therapy. A survey of Canadian oncologists was conducted online, with electronic data collection, and the analysis is reported descriptively. Measures collected included current practices with respect to the duration of adjuvant anti-HER2 therapy, perspectives on data regarding shorter durations of treatment, and interest in further trials on this subject. Responses were received from 42 providers across Canada. Half (50%, 21/42) reported having never recommended 6 months of anti-HER2 therapy. The primary reason physicians consider a shorter duration is in response to treatment-related toxicities (76%, 31/41). Most participants (79%, 33/42) expressed the need for more data to determine which patients can be safely and effectively treated with shorter durations. Patient factors such as young age, initial stage, hormone receptor status, and type of neoadjuvant chemotherapy were attributed to reluctance to offer shorter durations of treatment. Many respondents (83%, 35/42) expressed interest in participating in the proposed clinical trial of 6 months of anti-HER2 therapy. In contemporary Canadian practice, 12 months of anti-HER2 therapy remains the primary practice. Future trials are required to better define the role of shorter treatment durations.
Background: Unsolicited patient feedback (compliments and complaints) should allow the healthcare system to address and improve individual and overall patient, family, and staff experiences. We evaluated feedback at a tertiary cancer centre to identify potential areas for optimizing care delivery. Methods: unsolicited feedback submitted to the Patient Relations Department, relating to the Divisions of Medical and Radiation Oncology, at the Ottawa Hospital, was analyzed. Results: Of 580 individual reports submitted from 2016 to 2022, patient demographics were available for 97% (563/580). Median patient age was 65 years (range 17–101), and 53% (301/563) were female. The most common cancer types were breast (127/545, 23%) and gastrointestinal (119/545, 22%) malignancies, and most (64%, 311/486) patients had metastatic disease. Feedback was submitted mainly by patients (291/579, 50%), and predominantly negative (489/569, 86%). The main reasons for complaints included: communication (29%, 162/566) and attitude/conduct of care (28%, 159/566). While feedback rates were initially stable, an increase occurred from 2019 to 2021. Conclusions: Unsolicited feedback remains mostly negative, and relates to physician communication. If we are to drive meaningful changes in care delivery, more standardized means of assessing feedback and implementation strategies are needed. In addition, in an era of increased healthcare provider burnout, strategies to enhance formal positive feedback are also warranted.
Non-compliance and non-persistence with endocrine therapy for breast cancer is common and usually related to treatment-induced side effects. There are anecdotal reports that simply changing the time of day when taking endocrine therapy (i.e., changing morning dosing to evening dosing or vice versa) can reduce side effects.We conducted a literature review to evaluate whether changing the timing of tamoxifen and/or aromatase inhibitor administration impacted patient outcomes. No randomized control trials or prospective cohort studies that looked at time of day of endocrine therapy were identified through our review of literature from 1947 until August 2020.Given the rates of endocrine therapy non-compliance and non-persistence reported in the literature, ranging from 41-72% and 31-73%, respectively, simply changing the time of day when medications are taken could be an important strategy. We could identify no trials evaluating the effect of changes in timing of administration of endocrine therapy on breast cancer patient outcomes. Randomized control trials are clearly indicated for this simple and cost-effective intervention.
Abstract Purpose While adjuvant bisphosphonate use in early breast cancer (EBC) is associated with improvements in breast cancer-specific outcomes, questions remain around optimal bisphosphonate type, dose and scheduling. We evaluated a single zoledronate infusion in a prospective randomised trial. Methods Postmenopausal patients with EBC were randomised to receive a single infusion of zoledronate (4 mg IV) or 6-monthly treatment for 3 years. Outcomes measured were; Quality of Life (QoL; EQ-5D-5L), bisphosphonate-related toxicities, including acute phase reactions (APRs), recurrence-free survival (RFS), bone metastasis-free survival (BMFS) and overall survival (OS). Results 211 patients were randomized to either a single infusion (n = 107) or six-monthly treatment (n = 104). After 3 years of follow up there were no significant differences between the arms for QoL and most toxicity endpoints. APRs following zoledronate occurred in 81% (171/211) of patients (77.6% in single infusion arm and 84.6% in the 6-monthly group). While the frequency of APRs decreased over 3 years in the 6-monthly arm, they still remain common. Of 34/104 (32.7%) patients who discontinued zoledronate early in the 6-monthly treatment group, the most common reason was APRs (16/34, 47%). At the 3 year follow up, there were no differences between arms for RFS, BMFS or OS. Conclusion A single infusion of zoledronate was associated with increased patient convenience, less toxicity, and lower rates of treatment discontinuation. Despite the common clinical impression that APRs decrease with time, this was not observed when patients were specifically questioned. While the study is not powered for non-inferiority, longer-term follow-up for confirmation of RFS and OS rates is ongoing.
610 Background: Prognostic factors such as the IMDC criteria have included all types of targeted therapy. This study assesses clinical outcomes and provide benchmarks for mRCC pts treated specifically with 1L SUN in the real world to provide contemporary benchmarks for outcomes and survival. Methods: Clear cell mRCC pts initiating SUN as 1L therapy between 2010-2018 were included in a retrospective database study. Kaplan Meier analysis was used to estimate median time to treatment discontinuation (TTD) and overall survival (OS: time to death) by IMDC risk groups based on Karnofsky Performance Status < 80%, diagnosis to treatment interval < 1 year, anemia, neutrophilia, hypercalcemia and thrombocytosis. Results: Among 1,769 1L SUN pts with clear cell in the RW clinical database, 318 (18%) had favorable, 1,031 (58%) had intermediate and 420 (24%) had poor IMDC risk. Across the favorable, intermediate, and poor risk groups, pts had similar mean age in years, gender distribution, and year of SUN initiation (age: 63.8, 62.9 and 62.6; male: 74%, 75%, and 72%; SUN initiation year of 2010-2013: all 71%). In the favorable risk group, 99% received nephrectomy vs 88% in intermediate and 66% in poor risk group. Median TTD was 15.0, 8.5, and 4.2 months (mos) in the favorable, intermediate, and poor risk groups, respectively, and was 7.1 mos in the combined intermediate/poor risk groups. Median OS was 52.1, 31.5, and 9.8 mos in the favorable, intermediate, and poor risk groups, respectively, and was 23.2 mos in the combined intermediate/poor risk groups. Conclusions: This real world study based on a contemporary cohort of 1L SUN mRCC pts found a median OS of 52 mos which sets a new benchmark for clear cell mRCC in the favorable risk group. OS in the intermediate and poor risk groups are similar to previous reports. This affects pt counselling and clinical trial design.
Abstract Background International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (IMDC) risk groups are important when considering therapeutic options for first-line treatment. Materials and Methods Adult patients with clear cell mRCC initiating first-line sunitinib between 2010 and 2018 were included in this retrospective database study. Median time to treatment discontinuation (TTD) and overall survival (OS) were estimated using Kaplan-Meier analysis. Outcomes were stratified by IMDC risk groups and evaluated for those in the combined intermediate and poor risk group and separately for those in the intermediate risk group with one versus two risk factors. Results Among 1,769 patients treated with first-line sunitinib, 318 (18%) had favorable, 1,031 (58%) had intermediate, and 420 (24%) had poor IMDC risk. Across the three risk groups, patients had similar age, gender, and sunitinib initiation year. Median TTD was 15.0, 8.5, and 4.2 months in the favorable, intermediate, and poor risk groups, respectively, and 7.1 months in the combined intermediate and poor risk group. Median OS was 52.1, 31.5, and 9.8 months in the favorable, intermediate, and poor risk groups, respectively, and 23.2 months in the combined intermediate and poor risk group. Median OS (35.1 vs. 21.9 months) and TTD (10.3 vs. 6.6 months) were significantly different between intermediate risk patients with one versus two risk factors. Conclusion This real-world study found a median OS of 52 months for patients with favorable IMDC risk treated with first-line sunitinib, setting a new benchmark on clinical outcomes of clear cell mRCC. Analysis of intermediate risk group by one or two risk factors demonstrated distinct clinical outcomes. Implications for Practice This analysis offers a contemporary benchmark for overall survival (median, 52.1 months; 95% confidence interval, 43.4–61.2) among patients with clear cell metastatic renal cell carcinoma who were treated with sunitinib as first-line therapy in a real-world setting and classified as favorable risk according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group classification. This study demonstrates that clinical outcomes differ between IMDC risk groups as well as within the intermediate risk group based on the number of risk factors, thus warranting further consideration of risk group when counseling patients about therapeutic options and designing clinical trials.
Concerns exist regarding increased toxicities, including endocrine therapy toxicity, with concurrent radiation and endocrine therapy in early breast cancer (EBC). We present a pragmatic, randomized trial comparing concurrent versus sequential endocrine and radiotherapy in hormone-responsive EBC. In this multicenter trial, patients were randomized to receive adjuvant endocrine therapy concurrent with, or sequential to, radiotherapy. The primary outcome was change in endocrine therapy toxicity from baseline to 3 months post radiotherapy using the Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES) score. From September 2019 to January 2021, 133 patients were randomized to concurrent endocrine and radiotherapy, and 127 to sequential treatment. Most patients were post-menopausal (72.7%, 189/260) with stage 1 disease (65.8%, 171/260). Tamoxifen was the endocrine therapy of choice for 69.6% (181/260) of patients, and an aromatase inhibitor for the remainder. The median total radiation dose and fractions were 40.1 Gray (range 26-50) and 15 fractions (range 5-25), respectively. For the primary outcome of change in endocrine therapy toxicity per FACT-ES scores from baseline to 3 months post radiotherapy, no significant difference was found between the groups (median [range] = -4.9 (-82, 38.8) for concurrent and -5.1 (-42, 40) for sequential,
Abstract Background: HER2+ mBC remains incurable, thus novel HER2-directed therapies including chemotherapy-free options are needed. Approximately 50% of HER2+ mBC is also HR+, making the estrogen pathway an additional therapeutic target. The CDK4/6 inhibitor palbo + endocrine therapy fulv is approved for HER2−/HR+ mBC. Targeting all 3 pathways may further improve outcomes in pts with HER2+/HR+ mBC. Zani is a bispecific HER2-targeted antibody that binds HER2 in a unique trans configuration, driving multiple mechanisms of action. A prior analysis of the current single-arm, phase 2a study (NCT04224272) demonstrated antitumor activity and a tolerable safety profile for zani + palbo + fulv in heavily pretreated pts with HER2+/HR+ mBC. Enrollment has been completed; here we report the primary endpoint of PFS at 6 mo (PFS6) and other endpoints. Methods: Eligible pts had HER2+ (by local HER2 testing) and HR+, unresectable, locally advanced or mBC; ECOG PS ≤1; prior treatment with at least trastuzumab, pertuzumab, and T-DM1; and no prior CDK4/6 inhibitor. Pts received zani (20 mg/kg Q2W) + palbo + fulv (standard doses)—recommended doses determined in Part 1 assessment. The Part 2 primary endpoint was PFS6. Other endpoints included median PFS (mPFS), confirmed objective response rate (RECIST v1.1), disease control rate, and duration of response. PAM50 analysis was exploratory. A centrally confirmed HER2+ (ccHER2) subset was analyzed post hoc. Results: As of August 3, 2023, 51 pts (median age [range] 54 yr [36-77]) received zani + palbo + fulv treatment with a median follow-up time of 16.1 mo. Of the 51 pts, 32 (63%) were ccHER2+. Nine pts (18%) remained on treatment; median (range) duration of zani treatment was 8.4 (1.0-29.5) mo. In the metastatic setting, pts received a median (range) of 4 (1-12) prior systemic regimens, 3 (1-10) prior different HER2-targeted therapies, and 1 (0-5) prior endocrine therapy; 12 (24%) pts had prior T-DXd and 11 (22%) had prior fulv. The primary endpoint of PFS6 was 67% (69% in ccHER2+ subset). The mPFS was 11.7 mo (14.9 mo in ccHER2+ subset). See Table 1 for other efficacy endpoints. PAM50 subtyping was available for 29 pts (57%; 1 basal like; 16 HER2 enriched; 12 luminal B). Compared with HER2 enriched, luminal B was associated with numerically, but not statistically, longer mPFS (11.7 vs 9.3 mo; P=0.74) and similar PFS6 (66.7% vs 62.5%). The most common (>20%) treatment (zani, palbo, and/or fulv)-related adverse events (TRAEs) were diarrhea (80%), neutrophil count decrease/neutropenia (59%), nausea (39%), stomatitis (37%), anemia (29%), vomiting (25%) and asthenia (24%). Grade ≥3 TRAEs in ≥2 pts were neutrophil count decrease/neutropenia (53%), diarrhea (14%), anemia (10%), thrombocytopenia (6%), hypokalemia (4%), and hypomagnesemia (4%). One serious TRAE (transaminases increased) was reported. AEs of special interest: 6 pts with cardiac events (all LVEF decrease; 5 pts with grade 1 or 2 events, 1 pt with a grade 3 event) and 2 pts with infusion-related reactions (both grade 1). Three pts discontinued palbo due to an AE; 1 pt discontinued zani and fulv due to an AE. No treatment-related deaths were reported. Conclusions: Zani + palbo + fulv showed a promising PFS6 and mPFS with durable responses. The safety profile was manageable. These results support further development of a novel chemotherapy-free treatment regimen for heavily pretreated pts with HER2+/HR+ mBC. Table 1. Efficacy of Triplet Regimen (Zani + Palbo + Fulv) for HER2+/HR+ mBC a Patients with measurable disease (n=46 all pts; n=29 ccHER2+ subset). b Defined as best response of CR, PR, non-CR/non-PD (for patients who have only non-target lesions) or SD per RECIST 1.1. c Patients with DOR (n=16 all pts; n=14 ccHER2+ subset). cBOR, confirmed best overall response; ccHER2+, centrally confirmed HER2+; CI, confidence interval; cORR, confirmed objective response rate; CR, complete response; DCR, disease control rate; DOR, duration of response; HER2+, human epidermal growth factor receptor 2 positive; HR+, hormone receptor positive; mBC, metastatic breast cancer; mo, month; PD, progressive disease; PFS, progression-free survival; PFS6, progression-free survival at 6 months; PR, partial response; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SD, stable disease. Citation Format: Santiago Escrivá-de-Romani, Juan Miguel Cejalvo, Emilio Alba, Jennifer Friedmann, Álvaro Rodríguez Lescure, Marie-France Savard, Rossanna C. Pezo, Maria Gion, Manuel Ruíz - Borrego, Erika Hamilton, Timothy Pluard, Marc Webster, Muralidhar Beeram, Hannah Linden, Cristina Saura, Diana Shpektor, Bob Salim, Phoebe Harvey, Sara Hurvitz. Primary results from a phase 2a study of zanidatamab (zani) + palbociclib (palbo) + fulvestrant (fulv) in HER2+/HR+ metastatic breast cancer (mBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr LBO1-04.
There is strong interest from patients, researchers, the pharmaceutical industry, medical journal editors, funders of research, and regulators in sharing clinical trial data for secondary analysis. However, data access remains a challenge because of concerns about patient privacy. It has been argued that synthetic data generation (SDG) is an effective way to address these privacy concerns. There is a dearth of evidence supporting this on oncology clinical trial data sets, and on the utility of privacy-preserving synthetic data. The objective of the proposed study is to validate the utility and privacy risks of synthetic clinical trial data sets across multiple SDG techniques.
