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Introduction: Dual HER2 targeting improved pCR rates (ypT0ypN0) compared with Herceptin plus chemotherapy in the TRYPHAENA and NeoSphere registration trials. Pertuzumab-containing regimens (FEC-THP and TCHP) were adopted at the Kent Oncology Centre (KOC) following national funding approval in December 2016. Methods: A retrospective study of 176 (stage 1-3) HER2+ breast cancer patients receiving HER2-directed NACT at KOC between November 2014- December 2018 was conducted. Single targeting treatment (S) used FEC-TH. Dual targeting (D) regimens were FEC-THP or TCHP. Data was collected on age, stage, grade, HER2 and ER status, treatment regimen, treatment completion, pCR (ypT0ypN0) status, and echocardiogram results. Results: 51 patients received single HER2 targeted FEC-TH prior to funding approval for Pertuzumab. 125 patients received dual HER2 targeted agents (60 FEC-THP, 65 TCHP). A slight excess of ER negative and node positive cancers was seen in the S group. Dual targeting increased pCR rates: 50.4% (D) vs 37.2% (S). Overall, pCR rates did not differ between the two D regimens (50% vs 50.7% for FEC-THP and TCHP respectively). Amongst D treated patients, pCR rates were greater in ER negative tumours with the highest pCR rates seen in those receiving TCHP. For ER positive patients both D regimens modestly increased pCR with no clear benefit to TCHP (table 1). FEC-THFEC-THPTCHPn516065pCR ERpos (%)414745pCR ERneg (%)335471 Early chemotherapy discontinuation rates were similar in both groups but interruptions in trastuzumab (H) treatment were more common in D, particularly the TCHP group (table 2). FEC-THFECTHPTCHPChemo stopped early19% (6)20% (12)20% (13)H stopped early0% (0)3% 2)0% (0)H± Pinterrupted2% (1)6.6% (4)12.3% (8) Conclusion: A substantial increase in pCR rates was observed with dual targeting, regardless of ER and nodal status, reproducing the registration trial data in real world clinical practice. pCR rates were greatest in D treated patients with ER negative cancers, regardless of treatment regimen. TCHP was the most effective D regimen in ER negative patients but did not deliver superior pCR rates to FEC-THP in ER positive breast cancers. Substantially more cardiac toxicity and H treatment interruptions were observed with D, particularly with TCHP therapy. Citation Format: Jessica Little, Samantha Forner, Van Sim, Russell Burcombe, Rema Jyothirmayi, Jennifer Louise Glendenning. The differential impact of non-anthracycline treatment regimens on pathological complete response (pCR) rates by ER status after neoadjuvant single or dual HER2 targeted therapy (NACT): A single centre experience [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-31.

Historically, HER2-positive breast cancer had a poor prognosis. The development of molecul ar ther apies that target the HER2 receptor has TR ansformed outcomes. Here, the evidence on Anti-HER2 therapies is summarised

Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (s.c.) trastuzumab, delivered via single-use injection device (SID), over the intravenous (i.v.) formulation (Cohort 1 of the PrefHer study: NCT01401166). Here, we report patient preference, healthcare professional satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where s.c. trastuzumab was delivered via hand-held syringe.Patients were randomized to receive four adjuvant cycles of 600 mg fixed-dose s.c. trastuzumab followed by four cycles of standard i.v. trastuzumab, or vice versa. The primary endpoint was overall preference proportions for s.c. or i.v., assessed by patient interviews in the evaluable ITT population.A total of 245 patients were randomized to receive s.c. followed by i.v. and 243 received i.v. followed by s.c. (evaluable ITT populations: 235 and 232 patients, respectively). s.c. was preferred by 415/467 [88.9%; 95% confidence interval (CI) 85.7-91.6; P0.0001; two-sided test against null hypothesis of 65% s.c. preference]; 45/467 preferred i.v. (9.6%; 95% CI 7-13); 7/467 indicated no preference (1.5%; 95% CI 1-3). Clinician-reported adverse events occurred in 292/479 (61.0%) and 245/478 (51.3%) patients during the pooled s.c. and i.v. periods, respectively (P0.05; 2 × 2 χ(2)); 16 patients (3.3%) in each period experienced grade 3 events; none were grade 4/5.PrefHer revealed compelling and consistent patient preferences for s.c. over i.v. trastuzumab, regardless of SID or hand-held syringe delivery. s.c. was well tolerated and safety was consistent with previous reports, including the HannaH study (NCT00950300). No new safety signals were identified compared with the known i.v. profile in EBC. PrefHer and HannaH confirm that s.c. trastuzumab is a validated and preferred option over i.v. for improving patients' care in HER2-positive breast cancer.NCT01401166.

Background: The global COVID-19 pandemic has placed unprecedented burden on individual oncology patients, oncology departments, hospitals and national health systems. In order to protect individual patients from the risk of COVID-19 infection as well as improve capacity for COVID-19 patient management, a series of national and internationally agreed measures were proposed. During the first wave of infections the virulence and effect on cancer patients was not known. It is vitally important that the measures implemented to combat these risks are assessed and evaluated in order to learn best how to manage potential future waves of known and unknown viral infections.Methods: The international ESMO COVID-19 guidelines and national (NICE) guidelines were implemented across Kent, UK. All changes to treatment regimens were audited to assess what were the most frequent changes and in which patient groups could these be implemented. Data was subdivided for both early and advanced breast cancer as well as ER+, HER2+ or triple negative disease.Results: We collected full treatment history from 1,718 breast cancer patients currently receiving active oncology treatments. We were able to change treatment regimens due to COVID19 for 32.8% of patients. Of these 27.1% were early breast cancer patients compared with 43.7% were those with advanced metastatic disease. The most common changes for neoadjuvant changes were proceeding to surgery before completion of planned chemotherapy (10.2%), switch to 3 weekly Paclitaxel (10%) and chemotherapy break (8%). For adjuvant patients the most common changes included postponement of bisphosphonates (70.8%), chemotherapy break (13.5%), and curtailment to 6 months of adjuvant Trastuzumab (10.4%). For our palliative patients the most common changes included delay CDK4/6 inhibitor treatment (79.2%), postponement of bisphosphonates (24.8%), break in HER2 antibody (9.6%) and break in chemotherapy (8%).Conclusions: A large proportion of breast cancer oncology patients were deemed suitable to have a change in original planned treatment. We are fortunate to have comparatively large number of treatment options that can be customised on a patient basis to individual reduce risk of COVID-19. Further analysis is needed over time to compare the oncological outcomes of those in whom treatment was changes from the current gold standards of care. Citation Format: Simon N Rodney, Charlotte Abson, Russell Burcombe, Rema Jyothirmayi, Catherine Harper-Wynne. Changes in management of breast cancer patients during first wave of COVID19, throughout the area of Kent, United Kingdom. An audit of ESMO guideline implementation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-06.