- Email: [email protected]
Carboplatin-containing neoadjuvant chemotherapy for triple negative breast cancer (TNBC): A propensity score-matched study
abstracts
Annals of Oncology
Table: 190P
191P
Conclusions: The factors associated with aCT use in the elderly are similar to those usually found in younger age groups. By highlighting an OS benefit, even in the “very old” subgroup, our results may help clarifying the role of aCT in elderly patients. Legal entity responsible for the study: Houvenaeghel Gilles. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Adjuvant chemotherapy in elderly breast cancer patients: Pattern of use and impact on overall survival 192P
A. Berthelot1, A. De Nonneville1, J.-M. Classe2, M. Cohen3, F. Reyal4, C. Mazouni5, M.P. Chauvet6, A. Martinez7, N. Chopin8, E. Daraı¨9, C. Coutant10, R. Rouzier11, A.-S. Azuar12, P. Guimbergues13, C. Tunon De Lara14, R. Villet15, M. Bannier3, A. Gonc¸alves1, G. Houvenaeghel4 1 Medical Oncology, Institute Paoli Calmettes, Marseille, France, 2Surgical Oncology, ICO Institut de Cancerologie de l’Ouest Rene´ Gauducheau, Saint-Herblain, France, 3Surgical Oncology, Institute Paoli Calmettes, Marseille, France, 4Surgical Oncology, Institut Curie, Paris, France, 5Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France, 6 Surgical Oncology, Institute Oscar Lambret, Lille, France, 7Surgical Oncology, IUCT Oncopole, Toulouse, France, 8Surgical Oncology, Centre Le´on Berard, Lyon, France, 9 Surgical Oncology, Hopital Tenon, Paris, France, 10Surgical Oncology, Centre GeorgesFranc¸ois Leclerc (Dijon), Dijon, Cedex, France, 11Surgery, Institut Curie, Paris, France, 12 Surgical Oncology, CH de Grasse, Grasse, France, 13Surgical Oncology, Institute Jean Perrin, Clermont-Ferrand, France, 14Surgical Oncology, Institute Bergonie, Bordeaux, France,15Surgical Oncology, Hopital Diaconesses, Paris, France Background: Elderly breast cancer (BC) patients have been underrepresented in clinical trials whereas 60% of deaths from BC occur in women aged 65 years and older. The management of elderly women with early BC requires careful evaluation of risks and benefits of available treatment options. Clinical trials for elderly patients in the adjuvant setting are lacking, and efficacy results obtained in general population cannot be directly extrapolated to elderly patients without specific evidences. Therefore, we examined factors associated with the prescription of adjuvant chemotherapy (aCT) and the impact of this treatment on overall survival (OS) in a large cohort of patients aged 65 years and older. Methods: Patients were retrospectively identified from a large cohort of 23,134 early BC patients who underwent primary surgery in 18 academic centres between 1990 and 2014. A binary logistic regression was built to identify the factors associated with aCT administration. The impact of aCT on OS was analysed using a multivariate Cox regression model including age, histology, grade, tumour size, lymphovascular invasion (LVI), nodal status and endocrine therapy (ET) and endocrine receptors (ER). A propensity score-based matching analysis was performed. Results: Of 6605 patients aged 65 years and older, 1493 received aCT (22.6%). Administration of aCT was predominantly associated with macroscopic lymph node involvement (LNi) and ER-negative status but common predictors, such as age < 80 years, ductal histology, tumour size 20mm, ET and tumour grade were also found as statistically significant. In a Cox model including age, histology, LVI, tumour size, LNi, ET, ER and grade, aCT was significantly associated with better OS (HR 0.71, 95% CI 0.58 to 0.86; p < 0.001). Ten-year OS estimates in case-matched patients for propensity score analysis were 76.8% (95% CI 76.6 to 77.1) in the aCT group vs. 61.5% (95% CI
v64 | Breast Cancer, Early Stage
Carboplatin-containing neoadjuvant chemotherapy for triple negative breast cancer (TNBC): A propensity score-matched study
M.V. Dieci1, C.A. Giorgi2, G. Griguolo2, S. Angelini1, F. Miglietta1, T. Giarratano2, C. Falci2, G. Faggioni2, G. Tasca2, E. Mioranza2, G. Vernaci1, A. Menichetti1, M. Mantiero1, E. Genovesi1, S. Frezzini1, T. Saibene5, S. Michieletto3, V. Guarneri1 1 Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy, 2Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy, 3Breast Surgery, Istituto Oncologico Veneto IRCCS, Padua, Italy Background: The value of adding carboplatin (Cb) to neoadjuvant chemotherapy for TNBC is debated. Current evidence supports the association between Cb use and increased pathological complete response (pCR) rate. However, treatment schedules and doses adopted in randomized trials were not always consistent with those used in clinical practice. Methods: Clinicopathological data of TNBC (ER & PgR<10%) patients treated at our Institution with neoadjuvant anthracycline and taxane (AT) with or without Cb were collected. Propensity score was used to control selection bias. Variables considered for matching were: age, Ki67, cT, cN, histologic grade, histotype, BRCA status. Tumor infiltrating lymphocytes (TILs) were not used as matching variable since data were lacking for 39% of cases. The distribution of TILs in the two matched groups was similar (p ¼ 0.669). Binary logistic regression was used to test the association of Cb treatment with pCR (ypT0/is ypN0). Cox regression was used for survival analyses. Results: 166 patients were included: 61% treated with AT, 39% with ATþCb (all patients in this group received Cb AUC2 weekly administered concomitantly to the taxane segment). Main characteristics: median age 50 yrs, ductal histology 93%, grade 3 90%, cT > 2cm 86%, cN þ 57%, median TILs 10%, median Ki67 60%, BRCA mutated 10%. After propensity score matching, pCR rate was significantly higher for ATþCb vs AT: 52% vs 31% (OR 2.39 95%CI 1.04-5.50, p ¼ 0.040). In multivariable analysis, treatment with ATþCb maintained an independent association with pCR: OR 2.51 95%CI 1.03-6.11, P ¼ 0.043. The achievement of pCR was significantly associated with improved disease-free survival (HR 0.16, 95%CI 0.06-0.45). No difference in DFS was observed comparing ATþCb vs AT: HR 0.99, 95%CI 0.44-2.25. Conclusions: We confirmed in a clinical practice setting the association of Cb-containing neoadjuvant chemotherapy with higher pCR rates. Additional data are needed to clarify the impact on long-term survival. These data support the conditional positive recommendation for Cb inclusion in neoadjuvant chemotherapy for TNBC provided by the Italian Association of Medical Oncology Guidelines on Breast Cancer. Funding: Has not received any funding. Disclosure: M.V. Dieci: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genomic Health.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.018/5577995 by guest on 24 October 2019
(self): Celltrion; Research grant / Funding (self): Pfizer. S.J. Lee: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Stock option: Celltrion. M.J. Kim: Full / Part-time employment: Celltrion. S. Kim: Full / Part-time employment: Celltrion. S. Park: Full / Parttime employment: Celltrion. J.H. Bae: Full / Part-time employment: Celltrion. F.J. Esteva: Advisory / Consultancy: Celltrion; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.
abstracts
Annals of Oncology V. Guarneri: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.
193P
Impact of adjuvant trastuzumab emtansine (T-DM1) on incidence of metastatic breast cancer (mBC): An epidemiological model of patients with HER2-positive breast cancer (BC) who did not achieve pathological complete response (pCR) after neoadjuvant treatment (non-pCR)
Background: Progression from early BC (eBC) to mBC creates a substantial burden for pts and healthcare systems. The KATHERINE trial showed adjuvant T-DM1 reduced the risk of disease recurrence or death by 50% vs trastuzumab (T) in pts with HER2positive eBC with residual disease after neoadjuvant tx. The population level impact of T-DM1 on preventing relapsed mBC cases of HER2-positive, non-pCR eBC in 5 European countries (EU5) was estimated. Methods: An epidemiological model was developed and data from observational and clinical trial studies were used to inform BC variables (Table). Weighted averages of non-pCR rates by neoadjuvant tx and hormone receptor (HR) subtype were calculated and extrapolations from KATHERINE data were used to model disease progression and death. Results: Projected incidence of HER2-positive eBC in EU5 increased from 36,966 to 39,039 pts between 2020 -2029. Annual population eligible for adjuvant T-DM1 tx was stable at approximately 10,000 pts over the study time period. Total cases of mBC prevented with adjuvant T-DM1 from 2020 -2029 is projected to increase from 46 to 1732 with a cumulative total of 10,139 or 27% of total projected incident-relapsed mBC cases among pts with HER2-positive, non-pCR eBC. At year 10 (2029), the model projects 3798 pts prevented from developing mBC with T, thus a 46% decrease with TDM-1 relative to T. Findings were similar across EU5. Modeling estimates may not consider shifts in incidence or reflect actual practice or events occurring outside of the study period. Conclusions: Model outputs show a reduction of mBC due to T-DM1 beyond the maximum impact of T in eBC in EU5, thereby changing the epidemiology of HER2-positive BC over time, illustrating an even further decrease in current clinical and economic burden of this disease in these high-risk pts. Editorial acknowledgement: Purvi Shah, MD, of Ashfield Healthcare Communications (a UDG Healthcare plc company), supported by F Hoffmann-La Roche Ltd/Genentech, Inc. Legal entity responsible for the study: F Hoffmann-La Roche Ltd/Genentech, Inc. Funding: F Hoffmann-La Roche Ltd/Genentech, Inc. Disclosure: M.Y. Williamson: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann -La Roche Ltd. A. Tomar: Full / Part-time employment: ZS Associates International Inc. G.S. Jhuti: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann -La Roche Ltd. C. Revil: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann -La Roche Ltd. A. Kotzeva: Full / Part-time employment: F. Hoffmann -La Roche Ltd. K. Gururaj: Full / Part-time employment: ZS Associates International Inc.
Volume 30 | Supplement 5 | October 2019
Chemotherapy (CT)-induced anaemia in patients (pts) treated with dose-dense regimen: Results of the prospectively randomised anaemia substudy from the neoadjuvant GeparOcto study
H. Tesch1, S. Loibl2, K. Kast3, C. Jackisch4, V. Mo¨bus5, S. Buchen6, M. Untch7, C. Hanusch8, S. Seiler2, M. Weigel9, P.A. Fasching10, K. Rhiem11, J. Huober12, J.U. Blohmer13, C. Solbach14, C. Denkert15, V. Nekljudova2, T. Link3, A. Schneeweiss16 1 Centrum fu¨r H€ amatologie und Onkologie, Centrum fu¨r H€ amatologie und Onkologie Bethanien, Frankfurt, Frankfurt am Main, Germany, 2Department of Medicine and Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg, Germany, 3 Frauenheilkunde u.Geburtshilfe, Universit€ atsklinikum Dresden, Dresden, Germany, 4 Gyn€ akologie und Geburtshilfe, Klinikum Offenbach GmbH, Offenbach Am Main, 5 Germany, Gyn€ akologie und Geburtshilfe, Klinikum Frankfurt-Ho¨chst, Frankfurt am Main, Germany, 6Frauenheilkunde & Brustzentrum, Asklepio Paulinen Klinik Wiesbaden, Wiesbaden, Germany, 7Clinic for Gynecology, Gynecologic Oncology and Obstetrics, akologie und Geburtshilfe, Klinikum Helios Klinikum Berlin Buch, Berlin, Germany, 8Gyn€ zum Roten Kreuz Mu¨nchen, Germany, Munich, Germany, 9Frauenheilkunde u.Geburtshilfe, Leopoldina-Krankenhaus, Schweinfurt, Schweinfurt, Germany, 10 Department of Gynecology and Obstetrics, Universit€ atsklinik Erlangen, Erlangen, arer Brust- und Eierstockkrebs, Uniklinik Ko¨ln, Cologne, Germany, 11Zentrum Famili€ 12 Germany, Dept of Gynecology, Breast Center, Universitaetsfrauenklinik Ulm, Ulm, Germany, 13Gyn€ akologie mit Brustzentrum, Charite´-Universit€ atsmedizin, Berlin, Berlin, atsklinik Frankfurt, Germany, 14Klinik fu¨r Frauenheilkunde und Geburtshilfe, Universit€ 15 atsklinikum Marburg, Frankfurt, Germany, Institut fu¨r Pathologie UKGM, , Universit€ 16 Marburg, Germany, Gynecologic Oncology, Nationales Centrum fu¨r Tumorerkrankungen Heidelberg, Heidelberg, Germany Background: Use of parenteral (IV) ferric carboxymaltose (FCM) has been shown to be an efficient treatment of iron deficiency anaemia that can prevent blood transfusion. This substudy compared use of FCM with physician’s choice (PhCh) anaemia therapy in breast cancer (BC). Methods: In GeparOcto trial pts with primary BC were randomised to receive sequential, intensified, dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) or weekly paclitaxel/liposomal doxorubicin þ/- carboplatin (PM(Cb)) (Schneeweiss et al. Eur J Cancer). Pts with anaemia grade 2 (haemoglobin (Hb)<10g/dl), transferrin saturation (TSAT) 20% and serum ferritin <300ng/ml (amended to < 600ng/ml) were randomised to receive weekly FCM or PhCh (no treatment, oral iron, erythropoiesisstimulating agent, or both) anaemia therapy. Stratification factors were CT arm (iddEPC vs PM(Cb)) and planned PhCh. Primary objective compared the frequency of pts achieving Hb 11g/dl at 6 wks of therapy between both arms. Main secondary objectives were median time to achieve Hb 11g/dl and changes in iron parameters at baseline vs different time points. It was planned to include 184 pts per arm using 2sided exact Fisher test, with a ¼ 0.05 and power 80%. Results: Less than anticipated pts had CT-induced anaemia. 125 pts were randomised (62 in FCM, 63 in PhCh arm). Median age was 46 years (range 26-66); median levels of Hb, serum ferritin and TSAT were 9.6 (7.6-11.8)g/dl, 201 (3.0-551)ng/ml and 14.0% (4.0%-76.0%), respectively. After 6 wks, overall 40 (32.0%) pts (22 in FCM and 18 in PhCh arm; p ¼ 0.447) reached Hb 11g/dl. Median time to achieve Hb 11g/dl was 9.0 wks with FCM vs 10.6 wks by PhCh. Median Hb changes vs baseline were comparable in both arms during the treatment. 2 pts in FCM and 5 in PhCh arm (p ¼ 0.246) received blood transfusions until 6 wks of therapy. Conclusions: This is the first study investigating IV iron treatment for dose-dense CTinduced anaemia in BC. 32% of pts reached Hb 11g/dl at 6 wks. FCM treatment was not different than PhCh for anaemia therapy. Clinical trial identification: NCT02125344. Legal entity responsible for the study: German Breast Group (GBG).
doi:10.1093/annonc/mdz240 | v65
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.018/5577995 by guest on 24 October 2019
M.Y. Williamson1, A. Tomar2, G.S. Jhuti3, C. Revil4, A. Kotzeva3, K. Gururaj2 1 Pharmaceutical Division, Genentech, Inc., South San Francisco, CA, USA, 2Decision Analytics, ZS Associates International Inc., Frankfurt, Germany, 3Pharmaceutical Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 4Biostatistics, F. Hoffmann-La Roche Ltd, Basel, Switzerland
195P
Annals of Oncology
Table: 190P
191P
Conclusions: The factors associated with aCT use in the elderly are similar to those usually found in younger age groups. By highlighting an OS benefit, even in the “very old” subgroup, our results may help clarifying the role of aCT in elderly patients. Legal entity responsible for the study: Houvenaeghel Gilles. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Adjuvant chemotherapy in elderly breast cancer patients: Pattern of use and impact on overall survival 192P
A. Berthelot1, A. De Nonneville1, J.-M. Classe2, M. Cohen3, F. Reyal4, C. Mazouni5, M.P. Chauvet6, A. Martinez7, N. Chopin8, E. Daraı¨9, C. Coutant10, R. Rouzier11, A.-S. Azuar12, P. Guimbergues13, C. Tunon De Lara14, R. Villet15, M. Bannier3, A. Gonc¸alves1, G. Houvenaeghel4 1 Medical Oncology, Institute Paoli Calmettes, Marseille, France, 2Surgical Oncology, ICO Institut de Cancerologie de l’Ouest Rene´ Gauducheau, Saint-Herblain, France, 3Surgical Oncology, Institute Paoli Calmettes, Marseille, France, 4Surgical Oncology, Institut Curie, Paris, France, 5Surgical Oncology, Gustave-Roussy Cancer Campus, Villejuif, France, 6 Surgical Oncology, Institute Oscar Lambret, Lille, France, 7Surgical Oncology, IUCT Oncopole, Toulouse, France, 8Surgical Oncology, Centre Le´on Berard, Lyon, France, 9 Surgical Oncology, Hopital Tenon, Paris, France, 10Surgical Oncology, Centre GeorgesFranc¸ois Leclerc (Dijon), Dijon, Cedex, France, 11Surgery, Institut Curie, Paris, France, 12 Surgical Oncology, CH de Grasse, Grasse, France, 13Surgical Oncology, Institute Jean Perrin, Clermont-Ferrand, France, 14Surgical Oncology, Institute Bergonie, Bordeaux, France,15Surgical Oncology, Hopital Diaconesses, Paris, France Background: Elderly breast cancer (BC) patients have been underrepresented in clinical trials whereas 60% of deaths from BC occur in women aged 65 years and older. The management of elderly women with early BC requires careful evaluation of risks and benefits of available treatment options. Clinical trials for elderly patients in the adjuvant setting are lacking, and efficacy results obtained in general population cannot be directly extrapolated to elderly patients without specific evidences. Therefore, we examined factors associated with the prescription of adjuvant chemotherapy (aCT) and the impact of this treatment on overall survival (OS) in a large cohort of patients aged 65 years and older. Methods: Patients were retrospectively identified from a large cohort of 23,134 early BC patients who underwent primary surgery in 18 academic centres between 1990 and 2014. A binary logistic regression was built to identify the factors associated with aCT administration. The impact of aCT on OS was analysed using a multivariate Cox regression model including age, histology, grade, tumour size, lymphovascular invasion (LVI), nodal status and endocrine therapy (ET) and endocrine receptors (ER). A propensity score-based matching analysis was performed. Results: Of 6605 patients aged 65 years and older, 1493 received aCT (22.6%). Administration of aCT was predominantly associated with macroscopic lymph node involvement (LNi) and ER-negative status but common predictors, such as age < 80 years, ductal histology, tumour size 20mm, ET and tumour grade were also found as statistically significant. In a Cox model including age, histology, LVI, tumour size, LNi, ET, ER and grade, aCT was significantly associated with better OS (HR 0.71, 95% CI 0.58 to 0.86; p < 0.001). Ten-year OS estimates in case-matched patients for propensity score analysis were 76.8% (95% CI 76.6 to 77.1) in the aCT group vs. 61.5% (95% CI
v64 | Breast Cancer, Early Stage
Carboplatin-containing neoadjuvant chemotherapy for triple negative breast cancer (TNBC): A propensity score-matched study
M.V. Dieci1, C.A. Giorgi2, G. Griguolo2, S. Angelini1, F. Miglietta1, T. Giarratano2, C. Falci2, G. Faggioni2, G. Tasca2, E. Mioranza2, G. Vernaci1, A. Menichetti1, M. Mantiero1, E. Genovesi1, S. Frezzini1, T. Saibene5, S. Michieletto3, V. Guarneri1 1 Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy, 2Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy, 3Breast Surgery, Istituto Oncologico Veneto IRCCS, Padua, Italy Background: The value of adding carboplatin (Cb) to neoadjuvant chemotherapy for TNBC is debated. Current evidence supports the association between Cb use and increased pathological complete response (pCR) rate. However, treatment schedules and doses adopted in randomized trials were not always consistent with those used in clinical practice. Methods: Clinicopathological data of TNBC (ER & PgR<10%) patients treated at our Institution with neoadjuvant anthracycline and taxane (AT) with or without Cb were collected. Propensity score was used to control selection bias. Variables considered for matching were: age, Ki67, cT, cN, histologic grade, histotype, BRCA status. Tumor infiltrating lymphocytes (TILs) were not used as matching variable since data were lacking for 39% of cases. The distribution of TILs in the two matched groups was similar (p ¼ 0.669). Binary logistic regression was used to test the association of Cb treatment with pCR (ypT0/is ypN0). Cox regression was used for survival analyses. Results: 166 patients were included: 61% treated with AT, 39% with ATþCb (all patients in this group received Cb AUC2 weekly administered concomitantly to the taxane segment). Main characteristics: median age 50 yrs, ductal histology 93%, grade 3 90%, cT > 2cm 86%, cN þ 57%, median TILs 10%, median Ki67 60%, BRCA mutated 10%. After propensity score matching, pCR rate was significantly higher for ATþCb vs AT: 52% vs 31% (OR 2.39 95%CI 1.04-5.50, p ¼ 0.040). In multivariable analysis, treatment with ATþCb maintained an independent association with pCR: OR 2.51 95%CI 1.03-6.11, P ¼ 0.043. The achievement of pCR was significantly associated with improved disease-free survival (HR 0.16, 95%CI 0.06-0.45). No difference in DFS was observed comparing ATþCb vs AT: HR 0.99, 95%CI 0.44-2.25. Conclusions: We confirmed in a clinical practice setting the association of Cb-containing neoadjuvant chemotherapy with higher pCR rates. Additional data are needed to clarify the impact on long-term survival. These data support the conditional positive recommendation for Cb inclusion in neoadjuvant chemotherapy for TNBC provided by the Italian Association of Medical Oncology Guidelines on Breast Cancer. Funding: Has not received any funding. Disclosure: M.V. Dieci: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genomic Health.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.018/5577995 by guest on 24 October 2019
(self): Celltrion; Research grant / Funding (self): Pfizer. S.J. Lee: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Stock option: Celltrion. M.J. Kim: Full / Part-time employment: Celltrion. S. Kim: Full / Part-time employment: Celltrion. S. Park: Full / Parttime employment: Celltrion. J.H. Bae: Full / Part-time employment: Celltrion. F.J. Esteva: Advisory / Consultancy: Celltrion; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.
abstracts
Annals of Oncology V. Guarneri: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.
193P
Impact of adjuvant trastuzumab emtansine (T-DM1) on incidence of metastatic breast cancer (mBC): An epidemiological model of patients with HER2-positive breast cancer (BC) who did not achieve pathological complete response (pCR) after neoadjuvant treatment (non-pCR)
Background: Progression from early BC (eBC) to mBC creates a substantial burden for pts and healthcare systems. The KATHERINE trial showed adjuvant T-DM1 reduced the risk of disease recurrence or death by 50% vs trastuzumab (T) in pts with HER2positive eBC with residual disease after neoadjuvant tx. The population level impact of T-DM1 on preventing relapsed mBC cases of HER2-positive, non-pCR eBC in 5 European countries (EU5) was estimated. Methods: An epidemiological model was developed and data from observational and clinical trial studies were used to inform BC variables (Table). Weighted averages of non-pCR rates by neoadjuvant tx and hormone receptor (HR) subtype were calculated and extrapolations from KATHERINE data were used to model disease progression and death. Results: Projected incidence of HER2-positive eBC in EU5 increased from 36,966 to 39,039 pts between 2020 -2029. Annual population eligible for adjuvant T-DM1 tx was stable at approximately 10,000 pts over the study time period. Total cases of mBC prevented with adjuvant T-DM1 from 2020 -2029 is projected to increase from 46 to 1732 with a cumulative total of 10,139 or 27% of total projected incident-relapsed mBC cases among pts with HER2-positive, non-pCR eBC. At year 10 (2029), the model projects 3798 pts prevented from developing mBC with T, thus a 46% decrease with TDM-1 relative to T. Findings were similar across EU5. Modeling estimates may not consider shifts in incidence or reflect actual practice or events occurring outside of the study period. Conclusions: Model outputs show a reduction of mBC due to T-DM1 beyond the maximum impact of T in eBC in EU5, thereby changing the epidemiology of HER2-positive BC over time, illustrating an even further decrease in current clinical and economic burden of this disease in these high-risk pts. Editorial acknowledgement: Purvi Shah, MD, of Ashfield Healthcare Communications (a UDG Healthcare plc company), supported by F Hoffmann-La Roche Ltd/Genentech, Inc. Legal entity responsible for the study: F Hoffmann-La Roche Ltd/Genentech, Inc. Funding: F Hoffmann-La Roche Ltd/Genentech, Inc. Disclosure: M.Y. Williamson: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann -La Roche Ltd. A. Tomar: Full / Part-time employment: ZS Associates International Inc. G.S. Jhuti: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann -La Roche Ltd. C. Revil: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann -La Roche Ltd. A. Kotzeva: Full / Part-time employment: F. Hoffmann -La Roche Ltd. K. Gururaj: Full / Part-time employment: ZS Associates International Inc.
Volume 30 | Supplement 5 | October 2019
Chemotherapy (CT)-induced anaemia in patients (pts) treated with dose-dense regimen: Results of the prospectively randomised anaemia substudy from the neoadjuvant GeparOcto study
H. Tesch1, S. Loibl2, K. Kast3, C. Jackisch4, V. Mo¨bus5, S. Buchen6, M. Untch7, C. Hanusch8, S. Seiler2, M. Weigel9, P.A. Fasching10, K. Rhiem11, J. Huober12, J.U. Blohmer13, C. Solbach14, C. Denkert15, V. Nekljudova2, T. Link3, A. Schneeweiss16 1 Centrum fu¨r H€ amatologie und Onkologie, Centrum fu¨r H€ amatologie und Onkologie Bethanien, Frankfurt, Frankfurt am Main, Germany, 2Department of Medicine and Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg, Germany, 3 Frauenheilkunde u.Geburtshilfe, Universit€ atsklinikum Dresden, Dresden, Germany, 4 Gyn€ akologie und Geburtshilfe, Klinikum Offenbach GmbH, Offenbach Am Main, 5 Germany, Gyn€ akologie und Geburtshilfe, Klinikum Frankfurt-Ho¨chst, Frankfurt am Main, Germany, 6Frauenheilkunde & Brustzentrum, Asklepio Paulinen Klinik Wiesbaden, Wiesbaden, Germany, 7Clinic for Gynecology, Gynecologic Oncology and Obstetrics, akologie und Geburtshilfe, Klinikum Helios Klinikum Berlin Buch, Berlin, Germany, 8Gyn€ zum Roten Kreuz Mu¨nchen, Germany, Munich, Germany, 9Frauenheilkunde u.Geburtshilfe, Leopoldina-Krankenhaus, Schweinfurt, Schweinfurt, Germany, 10 Department of Gynecology and Obstetrics, Universit€ atsklinik Erlangen, Erlangen, arer Brust- und Eierstockkrebs, Uniklinik Ko¨ln, Cologne, Germany, 11Zentrum Famili€ 12 Germany, Dept of Gynecology, Breast Center, Universitaetsfrauenklinik Ulm, Ulm, Germany, 13Gyn€ akologie mit Brustzentrum, Charite´-Universit€ atsmedizin, Berlin, Berlin, atsklinik Frankfurt, Germany, 14Klinik fu¨r Frauenheilkunde und Geburtshilfe, Universit€ 15 atsklinikum Marburg, Frankfurt, Germany, Institut fu¨r Pathologie UKGM, , Universit€ 16 Marburg, Germany, Gynecologic Oncology, Nationales Centrum fu¨r Tumorerkrankungen Heidelberg, Heidelberg, Germany Background: Use of parenteral (IV) ferric carboxymaltose (FCM) has been shown to be an efficient treatment of iron deficiency anaemia that can prevent blood transfusion. This substudy compared use of FCM with physician’s choice (PhCh) anaemia therapy in breast cancer (BC). Methods: In GeparOcto trial pts with primary BC were randomised to receive sequential, intensified, dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) or weekly paclitaxel/liposomal doxorubicin þ/- carboplatin (PM(Cb)) (Schneeweiss et al. Eur J Cancer). Pts with anaemia grade 2 (haemoglobin (Hb)<10g/dl), transferrin saturation (TSAT) 20% and serum ferritin <300ng/ml (amended to < 600ng/ml) were randomised to receive weekly FCM or PhCh (no treatment, oral iron, erythropoiesisstimulating agent, or both) anaemia therapy. Stratification factors were CT arm (iddEPC vs PM(Cb)) and planned PhCh. Primary objective compared the frequency of pts achieving Hb 11g/dl at 6 wks of therapy between both arms. Main secondary objectives were median time to achieve Hb 11g/dl and changes in iron parameters at baseline vs different time points. It was planned to include 184 pts per arm using 2sided exact Fisher test, with a ¼ 0.05 and power 80%. Results: Less than anticipated pts had CT-induced anaemia. 125 pts were randomised (62 in FCM, 63 in PhCh arm). Median age was 46 years (range 26-66); median levels of Hb, serum ferritin and TSAT were 9.6 (7.6-11.8)g/dl, 201 (3.0-551)ng/ml and 14.0% (4.0%-76.0%), respectively. After 6 wks, overall 40 (32.0%) pts (22 in FCM and 18 in PhCh arm; p ¼ 0.447) reached Hb 11g/dl. Median time to achieve Hb 11g/dl was 9.0 wks with FCM vs 10.6 wks by PhCh. Median Hb changes vs baseline were comparable in both arms during the treatment. 2 pts in FCM and 5 in PhCh arm (p ¼ 0.246) received blood transfusions until 6 wks of therapy. Conclusions: This is the first study investigating IV iron treatment for dose-dense CTinduced anaemia in BC. 32% of pts reached Hb 11g/dl at 6 wks. FCM treatment was not different than PhCh for anaemia therapy. Clinical trial identification: NCT02125344. Legal entity responsible for the study: German Breast Group (GBG).
doi:10.1093/annonc/mdz240 | v65
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M.Y. Williamson1, A. Tomar2, G.S. Jhuti3, C. Revil4, A. Kotzeva3, K. Gururaj2 1 Pharmaceutical Division, Genentech, Inc., South San Francisco, CA, USA, 2Decision Analytics, ZS Associates International Inc., Frankfurt, Germany, 3Pharmaceutical Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 4Biostatistics, F. Hoffmann-La Roche Ltd, Basel, Switzerland
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