Health technology assessments and value frameworks are becoming increasingly important for clinical decision-making. Most of these frameworks, however, focus on value to payers rather than patients and healthcare providers and may ignore other sources of economic value such as patient and physician time cost, impact on productivity, and direct health system costs. This article focusses on fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in the treatment of HER2-positive breast cancer. We review relevant clinical evidence, examine data on time and resource use of the subcutaneous administration of trastuzumab compared with intravenous treatment and how it can be extrapolated to PH FDC SC, and discuss the value PH FDC SC can bring to patients and healthcare providers. We will also provide our own experiences of PH FDC SC from the healthcare (oncologist, healthcare economist, pharmacist) and patient point of view. The data, combined with our personal experiences, suggest that switching from intravenous pertuzumab and trastuzumab to PH FDC SC could reduce non-drug costs for healthcare providers treating patients with HER2-positive breast cancer through time savings and other economic benefits. Furthermore, PH FDC SC could also save patient time given its shorter administration and post-injection observation time versus intravenous infusions, potentially resulting in reduced productivity loss. These benefits could be applied to other subcutaneous formulations, either currently available or in development.
Background: Stage II-III TNBC retains a poor outcome despite high chemosensitivity. Patients (pts) with pCR after neoadjuvant chemotherapy have a good prognosis whereas non-responding pts have a 25-40% risk of distant relapse at 5 years. pCR is thus a major goal in TNBC. We previously reported that TNLABC benefit the most of dose dense dose intense cyclophosphamide (C)-epirubicin (E) (S.Giacchetti; BJC, 2014) Aim: To confirm these results prospectively and analyze the predictive factors of response to high dose chemotherapy in TNBC. Patients and methods: From january 2009 to april 2015 non inflammatory TNLABC received high dose C (1200 mg/m2 d1 qw 2) with E (75 mg/m2/ d1 qw2) for 6 cycles. The pts had a breast biopsy with frozen tissue. We performed molecular studies: qRT-PCR for AR, FOXA1, PI3K and FASAY technic for p53 mutation.The percentage of stromal Tumor-infiltrating lymphocytes (TILs) was also evaluated by two independent pathologists and assessed as a continuous variable. A18F-FDG PET/CT was performed initially and after 2 courses of chemotherapy and the metabolic answer assessed as a variation of the tumor uptake (ΔSUVmax). We report here the pathological complete response (pCR) (absence of infiltrative carcinomas in the breast and in the lymph nodes) and the factors associated with pCR. Results: The characteristics of the 74 pts are listed in table 1. The median age is 48 years old, 48 pts (65.8%) are premenopausal and 79% did not have any family history of breast cancers. TIL was divided in 3 groups < 10 % (26 pts, 40 %); 10-50 % (30 pts, 46 %) > 50% (9 pts, 14 %). Pathological response was assessed in 66 pts, one pt progressed during chemotherapy and 6 pts did not undergo surgery yet. 28 pts were in pCR (42.4 %). With a median follow up of 25 months, 13 pts (17.8 %) progressed and 8 (11%) died. Table 1: Patients characteristics and pCR according to tumor features and metabolic responseCharacteristicsNumber of pts (%)N of pts evaluated for pCRpCR (%)OR [IC 95%]p-valueTumor size T2363519 (54)10.04T337319 (29)0.34 [0.12 ; 0.96]Nodal status N0363315 (46)10.62N1/N2/N3 24/11/33313 (39)0.78 [0.29 ; 2.07]Histological grade: 2660 (0) 0.04*3676028 (47)TILs <10 %26 (40)2510 (40)10.02610-50 %30 (46)267 (27)0.55 [0.17 ; 1.80]≥ 509 (14)9 7 (78)5.25 [0.90 ; 30.62]P53 Mutated54 (89)5121 (41)10.43WT7 (12)53 (60)2.14 [0.33; 13.96]AR Negative43 (83)4318 (42)10.46Positive 9 (17)95 (56)1.74 [0.41 ; 7.38]FOXA1 Negative40 (77)4015 (38)10.08Positive 12 (23)128 (60) 3.33 [0.86 ; 12.99]Molecular Apocrine8 (17)85 (63)10.19TN38 (83)3814 (37)0.35 [0.07 ; 1.69]PI3K Non mutated44 (88)4419 (43)10.75Mutated6 (12)63 (50)1.31 [0.24 ; 7.26]SUVmax at 2 courses0.0001< 70 %27 (53)221 (5)1≥ 70 %24 (47)2318 (78)79.2 [8.48 ; 739.82]* Measured with a Fisher Test Tumor size, tumor grade, percentage of TILs, the change in 18F-fluorodeoxyglucose tumor uptake (ΔSUVmax) were significantly associated with pCR at univariate analysis. Only one factor remained significant at multivariate analysis, the ΔSUVmax, OR: 0.04 [0.007- 0.27], p = 0.0008. Conclusion: In this prospective phase III trial we confirm the efficacy of a dose dense EC in TNBC. The metabolic response evaluated with 18 F-FDG PET/CT is a strong and reliable predictor of pCR and could allow an early change of treatment for the non responders. A clinical trial is planned to test this strategy. Citation Format: Giacchetti S, De Roquancourt A, Groheux D, Piron P, Lehmann-che J, Cuvier C, Resche-rigon M, Albiter M, Roche B, Frank S, Hamy A-S, Teixeira L, Marty M, Lalloum M, Espié M. Prediction of pathological response (pCR) to neoadjuvant dose dense and intense cyclophosphamide and anthracycline in a prospective series of triple negative locally advanced breast cancers (TNLABC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-08.
Background Young age is a known poor prognosis factor in early stage breast cancer (BC). Its value is less documented for metastatic BC (MBC). Guidelines state that age should not guide the treatment strategy. We used the ESME database to evaluate the impact of age at MBC diagnosis on overall survival (OS). Patients and Methods ESME is a unique national cohort, collecting retrospective data using clinical trial-like methodology. It included all consecutive MBC patients (pts) who initiated at least 1 treatment in one of the 18 participating French cancer centers between 01/01/2008 and 12/31/2014. The database was locked on 12/8/2016. Primary objective were the comparisons of MBC characteristics between age groups (<40, 40 to 60 and >60 years (y)) and the evaluation of the impact of age at MBC diagnosis on OS. Interaction between age and tumor subtype was tested using a Cox regression model. ResultsAmong 16 703 included pts, 1539 had no information on tumor receptors (ER/PR/HER2) and 682 had an exclusion criteria (unknown age, men or other cancer in the last 5y), leaving 14 482 for analysis. At the onset of MBC, 902 pts (6.2%), 6269 (43.3%) and 7311 (50.5%) were <40y, 40y to 60y and older than 60y respectively. Median follow-up was 54.8 months. Pts <40 had significantly more aggressive presentations than other age groups: more HER2+ (26.5%), and triple negative (26.4%) subtypes, more visceral involvement (57.1%), and shorter time to metastasis (26.9% between 6 to 24 months) (all p-value vs other age groups <0.0001). MBC characteristics according to age groups Age at MBC diagnosis (years)p-value <4040-60>60 Tumor subtype <0.0001HR+/HER2-425 (47.12)3816 (60.87)5262 (71.97) HR-/HER2-238 (26.39)1126 (17.96)884 (12.09) HER2+239 (26.5)1327 (21.17)1165 (15.93) Type of metastasis, N(%) <0.0001Bone only219 (24.31)1832 (29.23)2367 (32.41) Non visceral168 (18.65)1046 (16.69)1314 (17.99) Visceral514 (57.05)3389 (54.08)3623 (49.6) Time to first metastasis (months), N(%) <0.0001< 6304 (33.74)1882 (30.1)2107 (28.9) [6-12[65 (7.21)241 (3.85)209 (2.9) [12-24[177 (19.64)760 (12.15)564 (7.7) ≥24355 (39.4)3370 (53.89)4416 (60.53) Number of metastatic sites, N(%) 0.51 site709(78.6)4948 (78.93)5805 (79.4) 2 sites163(18.07)1130 (18.03)1313(17.96) ≥3 sites30(3.33)191 (3.05)193 (2.64) Overall, median OS was identical in the different age groups: 39.1, 41.1 and 39.8 months for pts <40, 40-60 and >60, respectively (p=0.2). Tumor subtype and age showed a significant interaction on OS (p<0.0001), especially among HER2+ MBC Overall survival (months) according to tumor subtypes and age groups Age groups (years)p-value (log-rank)Tumor subtype<4040-60>60 HR+/HER2-46,4 (CI 95% 40.5-55.4)47,8 (CI 95% 46-50)44,2 (CI 95% 42.1-46.3)0.0023HER2+60,7 (CI 95% 45.6-76.4)50,4 (CI 95% 46.3-56.3)44 (CI 95% 38.8-48.9)<0.0001Triple negative14 (CI 95% 11.5-16.5)14,7 (CI 95% 13.7-15.9)15,7 (CI 95% 14.6-17.1)0.01 . Anti-HER2 with first-line treatment was given preferentially to young pts: 86.6, 81.9 and 74.9%for pts <40, 40-60 and >60, respectively (p<0.0001). Conclusion At onset of MBC, young age was associated with more aggressive presentations, however with no global impact on OS. Pts <40 with HER2+ disease carried a better prognosis, maybe related to therapy. Citation Format: Frank S, Tchokothe C, Carton M, Mouret-Fourme E, Dubot C, Campone M, Pistilli B, Dalenc F, Mailliez A, Levy C, D'Hondt V, Debled M, Leheurteur M, Coudert B, Perrin C, Gonçalves A, Uwer L, Ferrero J-M, Eymard J-C, Petit T, Mouret-Reynier M-A, Guesmia T, Bachelot T, Robain M, Cottu P. Impact of age at diagnosis of metastatic breast cancer on overall survival in the real-life "ESME" cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-10.
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