Abstract P2-08-22: Adjuvant trastuzumab effectiveness in a cohort of HER2-positive breast cancer Brazilian patients treated in a public hospital: The impact in public health planning compared to clinical trial data
Authors: Orlandini Leonardo F , Pimentel Franklin F , Carrara Hélio HA , Reis Francisco JC dos , de Andrade Jurandyr M , Tiezzi Daniel G 
Published: March 2020

Background: About 20% of breast cancer (BC) subtypes are classified as HER2-positive (HER2+), recognized as a biomarker for worse prognosis. Trastuzumab (T) is a monoclonal antibody approved to treat HER2+ early BC since 2006 and included in the World Health Organization (WHO)’s list of essential anticancer drugs since 2016. Despite this, access to this biological drug is far from the ideal, especially in low- and middle-income countries. The real-world benefit of cancer therapy is generally different from the benefit found in clinical trials. In order to better support public health planning, we analyzed the clinical benefit of adjuvant trastuzumab in a population-based cohort and compared its benefit with a consolidated phase 3 trial.

Methods: Clinical data from 1,969 BC patients treated from 1999 to 2013 in a Brazilian public hospital were retrospectively obtained from medical records; 467 were HER2+ (23.7%); 410 had information on the use of trastuzumab and were stages I, II or III. Information related to the price of trastuzumab was obtained on the internet on government websites.

Results: Out of 410 patients, 178 (43%) received T in association with chemotherapy (CT) and 232 (57%) received only CT. Although T-CT patients presented more clinical features related to a worse prognosis as younger and higher prevalence of stage III BC (Table 1) compared to CT group, T-CT group showed significant improvement of the adjusted disease specific-survival (DSS) (HR= 0.40; 95%CI 0.22 - 0.73; p&lt;0.0001).

Demographic and baseline disease characteristics of the patients.CharacteristicsNo trastuzumab (n=232)Trastuzumab (n=178)p-valueAge – average (years)57.851.4&lt;0.0001Histological subtype n(%)Ductal219 (94)172 (97)0.34Non-ductal13 (6)6 (3)Histological grade n(%)128 (12)16 (9)0.382124 (53)110 (62)364 (28)48 (27)NA16 (7)4 (2)Hormonal receptor (%)0.8Positive137 (59)108 (61)Negative95 (41)70 (39)Clinical stage n (%)0.01I (A+B)45 (19)17 (10)II (A+B)84 (36)66 (37)III (A+B+C)103 (44)95 (53)

The absolute increase in 5-years DSS was 14%, resulting in a number needed to treat (NNT) of 7.1, which is more favorable than the previous reported clinical data of absolute 5-years overall survival improvement with adjuvant T-CT of 9% (NNT= 11.1) (Slamon et al. 2011).

Until 2012, in Brazil, most patients received adjuvant trastuzumab from legal litigation with T being purchased by government on an individually basis; from 2013 to 2018, after a national government program, T was purchased centrally. Since 2019, there was an additional impact on T negotiations due to biosimilar T approval, although, to date, for Brazilian public health services only originator trastuzumab is available.

Considering these different scenarios and the price of 1 mg T, we estimated the costs with trastuzumab to prevent one death. (Table 2)

Estimated prices of trastuzumab of local population versus clinical trial data.1 mg T price (US$)T costs to prevent 1 death (clinical data) (US$ x1,000)T costs to prevent 1 death (local population) (US$ x1,000)Until 201211.229596132013-20182.50214137From 20191.5513285

Conclusions: Considering that the real-world population may present a higher incidence of advanced cases compared to populations of clinical trials, the clinical benefit of a drug may be even greater than estimated. In this study we showed a HER2+ BC population from an upper middle income country with a greater benefit for adjuvant trastuzumab. After arrival of biosimilars, the price of trastuzumab is expected to be reduced; in addition, local estimation of effectiveness may result in an even greater cost-benefit than that found in clinical trials, contributing to public health planning.

Citation Format: Leonardo F Orlandini, Franklin F Pimentel, Hélio HA Carrara, Francisco JC dos Reis, Jurandyr M de Andrade, Daniel G Tiezzi. Adjuvant trastuzumab effectiveness in a cohort of HER2-positive breast cancer Brazilian patients treated in a public hospital: The impact in public health planning compared to clinical trial data [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 P2-08-22.