ESMO Supporter 2018

Displaying One Session

ICM - Room 13 Proffered Paper session
Date
19.10.2018
Time
16:00 - 17:30
Location
ICM - Room 13
Chairs
  • Carlos Caldas (Cambridge, GB)
  • Suzette Delaloge (Villejuif, FR)
Proffered paper session - Breast cancer, early stage Proffered Paper session

184O - Distant disease-free survival (DDFS) according to response category in neoadjuvant endocrine therapy (NET): 6-Year analysis in phase III NEOS trial

Presentation Number
184O
Lecture Time
16:00 - 16:12
Speakers
  • Hiroji Iwata (Nagoya, JP)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

NEOS is a randomized phase III study that assessed the long-term prognosis of estrogen receptor positive (ER+) primary breast cancer (PBC) pts who received NET with/without adjuvant chemotherapy (CT). We presented the first report about the relationship between DFS and clinical response to NET at median follow-up 4Y in SABCS 2017. We now present new data corrected according to long follow-up (median 5.9Y).

Methods

Postmenopausal BC pts with ER +/HER2 negative, T1c-2, clinically node negative, and under 76 years old were enrolled at primary registration. Pts were treated by leterozole (LET) in weeks 24-28 after primary enrollment. Pts who experienced progression of disease (PD) during neoadjuvant phase were excluded at randomization and received systemic therapy driven by investigators before or after surgery. Pts who met eligibility criteria were randomized 1:1 to LET for 4.5-5 years after CT or LET alone for 4.5-5 years without CT after surgery. DFS/OS in patients showing CR, PR, SD or PD response to NET are secondary endpoints and DDFS is an exploratory endpoint.

Results

Between May 2008 and June 2013, 904 patients were enrolled at primary registration from 100 institutions in Japan and 21 pts were withdrawn during neoadjuvant phase. The median age was 63 years, T1c: 36%, T2: 64%, and progesterone receptor (PgR) +: 79%. Clinical response rates (CR, PR, SD and PD) were 2% (16pts), 48% (421pts), 46% (403pts) and 5% (43pts), respectively. In each response, 0% (0/16), 10.7% (45/421), 12.7% (51/403), and 44.2% (19/43) experienced DFS events and 0% (0/16), 5.2% (22/421), 7.2% (29/403) and 26% (11/43) experienced DDFS events. DDFS in PD pts to NET were statistically significantly worse than CR, PR, SD pts (p < 0.001, hazard ratio 4.83 (95% CI:2.52-9.29). The predictive markers of PD for NET were PgR status (P < 0.001) and Ki67 status (P = 0.041) in biopsy specimen among factors evaluated by multivariate analysis

Conclusions

The DDFS of PBC pts excluding PD pts to NET is excellent regardless of treatment with/without CT. NET with utilization of PD response as a prognostic marker can be considered as a standard treatment option for these patients.

Clinical trial identification

UMIN000001090.

Legal entity responsible for the study

CSPOR.

Funding

The parent NEOS study was sponsored by CSPOR (Comprehensive Support Project for Oncology Research), part of a Sponsored by CSPOR and Novartis and Chugai Pharmaceuticals provided funding to CSPOR.

Disclosure

H. Iwata: Research: Chugai, Novartis, MSD, Lilly; Honororia: Chugai, AstraZeneca, Daiichi Sankyo; Advisory Board: Daiichi Sankyo, Chugai, Lilly, Kyowa Hakko Kirin, Pfizer, Novartis, AstraZeneca. N. Masuda: Honoraria: Chugai, AstraZeneca, Pfizer, Takeda; Research: Chugai, Novartis, MSD, Eli-Lilly, AstraZeneca, Daiichi Sankyo, Kyowa- Kirin, Pfizer. T. Toyama: Research fund: Eisai, Kyowa Kirin, Takeda, Chugai, Novartis, Nippon Kayaku, Pfizer, Daiichi Sankyo; Advisory board: AstraZeneca. M. Kashiwaba: Honoraria: Chugai, AstraZeneca. Y. Ohashi: Honororia: Chugai, PHRF; Consultant: Chugai; Research fund: Eisai. All other authors have declared no conflicts of interest.

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Proffered paper session - Breast cancer, early stage Proffered Paper session

185O_PR - Serum assessment of non-adherence to adjuvant endocrine therapy (ET) among premenopausal patients in the prospective multicenter CANTO cohort

Presentation Number
185O_PR
Lecture Time
16:12 - 16:24
Speakers
  • Barbara Pistilli (Villejuif, FR)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

Previous studies demonstrated that younger patients (pts) with breast cancer (BC) are more likely to be non-adherent to adjuvant ET, leading to impaired prognosis.

Methods

The CANTO cohort (NCT01993498) is a French multicenter prospective longitudinal study that will include 12000 pts with recently diagnosed stage I-III BC, to characterize long-term impact of BC treatment toxicities. CANTO COMPLETE, a pre-defined sub study, aims to determine, in premenopausal pts who have been prescribed adjuvant ET, the prevalence and dynamic predictors of non-adherence, at 1 (M12), 3 (M36) and 5 (M60) years, using serum assessment of tamoxifen (TAM) and aromatase-inhibitors (AI) matched with pts’ self-declaration. TAM dosage has been determined by liquid chromatography-tandem mass spectrometry on 200 µL of serum. According to standard definitions, adherence to TAM has been defined as: non-adherent if TAM ≤15 ng/mL (≤40 nM), poorly-adherent if TAM 15-60 ng/mL (40-150 nM) and adherent if > 60 ng/mL (>150 nM).

Results

By December 2017, 11237 pts have been included in CANTO, of whom 1799 (16%) are premenopausal and have been prescribed and agreed to take ET: TAM 1496 (83.2%); TAM + LHRH-analogs (LHRH) 26 (1.4%); AI+LHRH 134 (7.5%); unknown 143 (7.9%).We present here the results of TAM plasma assessment at 1 year on all 1228 pts who reached 1 year of follow-up. Overall, 224 (18.2%) pts appeared not adequately adherent to TAM: 162 (13.2%) non-adherent and 62 (5.0%) poorly-adherent. Matching with pts’ self-declaration and clinical determinants of non-adherence will be presented.

Conclusions

At one year from initiation of TAM, plasma measurements show that a substantial proportion of premenopausal pts are not adequately adherent to this treatment. Poorly-adherent pts could benefit from metabolic and pharmacogenetic investigations. Identification of pts at risk of non-adherence allows early targeted interventions to promote adherence in this unique population.

Clinical trial identification

NCT01993498

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Proffered paper session - Breast cancer, early stage Proffered Paper session

Invited Discussant 184O and 185O

Lecture Time
16:24 - 16:39
Speakers
  • Helena M. Earl (Cambridge, GB)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30
Proffered paper session - Breast cancer, early stage Proffered Paper session

LBA12_PR - PERSEPHONE: 6 versus 12 months (m) of adjuvant trastuzumab in patients (pts) with HER2 positive (+) early breast cancer (EBC): Cost effectiveness analysis results

Presentation Number
LBA12_PR
Lecture Time
16:39 - 16:51
Speakers
  • Claire Hulme (Leeds, GB)
  • Peter Hall (Edinburgh, GB)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

Adjuvant trastuzumab has significantly improved outcomes for HER2+ EBC, using the 12m duration empirically adopted from pivotal registration trials. Given an annual per patient cost of trastuzumab treatment of over £30,000 (Euro35,000), a shorter duration has the potential to improve cost-effectiveness if efficacy is maintained.

Methods

The cost-effectiveness analysis was based on data from the PERSEPHONE trial, a phase III non-inferiority RCT comparing 6 to 12m Trastuzumab, the largest reduced-duration non-inferiority trial internationally. A landmark analysis 6 months into treatment was conducted, comparing costs and quality of life throughout follow-up (6m – 24m post treatment start). Multiple imputation was required to impute incomplete quality of life data. Quality Adjusted Life Years (QALYs) were adjusted for differences at baseline. Uncertainty is estimated using the non-parametric bootstrap method.

Results

4009 patients were disease free at 6m (6m: n=2000, 12m: n=2009) and therefore eligible for the analysis. Of these, 250 individuals (6m: n=132, 12m: n=118) had either no returned PQ forms or no returned treatment forms and therefore were excluded from the analysis.
The average costs for an individual in the 6m arm and 12 month arm were £2,538.64 (95% CI: £2,383.38 - £2700.72) and £12,333.83 (95% CI: £12,098.58 - £12,562.27), respectively, giving an average cost saving of £9,793.25 (95% CI: £9,515.86 - £10,071.64) per individual. Trastuzumab treatment and administration accounted for £9,699.58 (95% CI: £9,436.20 - £9.954.67) of this cost saving, the remaining arising from cardiac assessment and treatment costs and inpatient days. The average QALYs for an individual in the 6m arm and 12 month arm were 1.146 (95% CI: 1.131 – 1.161) and 1.128 (95% CI: 1.113 – 1.144), respectively, giving an average QALY difference of 0.018 (95% CI: -0.003 – 0.039). Thus, the 6m arm dominated with a probability of being cost effective of 100%.

Conclusions

6m of trastuzumab was shown to be cost effective compared to 12m with cost-savings and no evidence of a detriment to quality of life.

Clinical trial identification

Registry Name: ISRCTN Register. Registration Number: 52968807

Editorial Acknowledgement

None

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Proffered paper session - Breast cancer, early stage Proffered Paper session

186O - Tumor-infiltrating lymphocytes (TILs) as an independent prognostic factor for early HER2+ breast cancer patients treated with adjuvant chemotherapy and trastuzumab in the randomized ShortHER trial.

Presentation Number
186O
Lecture Time
16:51 - 17:03
Speakers
  • Maria Vittoria Dieci (Padova, IT)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

TILs are an established prognostic factor for triple negative breast cancer. We investigated the prognostic role of TILs for HER2+ early breast cancer patients enrolled in the prospective ShortHER trial.

Methods

The ShortHER study randomized 1254 patients with HER2+ early breast cancer to receive 9 weeks vs 1 year of adjuvant trastuzumab combined with chemotherapy (Conte, ASCO 2017). TILs were assessed for 855 cases on centralized HES slides according to recommendations (Salgado, Ann Oncol 2015). Metastasis-free survival (MFS) was calculated from randomization to distant disease recurrence or death. Median follow up was 72 months.

Results

Median TILs was 5% (Q1-Q3 1%-15%). Higher TILs were associated with hormone receptor-negative status (p < 0.001) and age <60 years (p = 0.008). There was no association with stage and PIK3CA mutation. Increased TILs were associated with better MFS (HR 0.69, 95%CI 0.54-0.88 for each 10% TILs increment, p = 0.003). 5-yrs MFS rates were 91%, 94% and 100% for TILs<20%, TILs > =20% & <50% and TILs > =50% (p = 0.013). Multivariable cox models confirmed TILs as independent prognostic factor (Table).

MULTIVARIATE COX MODELS FOR MFS
FactorsAll patients
Hormone Receptor neg
Hormone Receptor pos
HR (95% CI)pHR (95% CI)pHR (95% CI)p
TILs 10% increase0.67 (0.52-0.86)0.0010.72 (0.53-0.97)0.0310.57 (0.36-0.91)0.017
HR pos vs neg0.63 (0.39-1.00)0.049----
Stage I-II vs III0.31 (0.20-0.50)<0.0010.27 (0.13-0.59)0.0010.33 (0.19-0.60)<0.001
Age >60 vs < 601.02 (0.65-1.60)0.9361.44 (0.69-3.02)0.3370.82 (0.45-1.47)0.501

The association between 10% TILs increments and MFS was significant in the short (HR 0.49, 95%CI 0.29-0.82, p = 0.006) but not in the long arm (HR 0.84, 95%CI 0.65-1.10, p = 0.212). Patients with TILs <20% benefitted from long treatment (HR 0.76, 95%CI 0.60-0.97, p = 0.024), whereas for patients with TILs > =20% the HR favored the short arm (HR 2.79, 95%CI 0.98-7.96, p = 0.055; 8 events only). Interaction test showed p = 0.064 (arm*10% TILs increase) and p = 0.019 (arm*TILs binary variable with 20% cutoff).

Conclusions

TILs are an independent prognostic factor for HER2+ early breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Integration of TILs in prognostic algorithms can help refining risk stratification and guiding therapeutic de-escalation.

Clinical trial identification

EudraCT 2007-004326-25 Start date: 2007-11-15.

Legal entity responsible for the study

University of Modena and Reggio Emilia; University of Padova.

Funding

Agenzia Italiana del Farmaco (AIFA).

Disclosure

P.F. Conte: Speaker's bureau: Roche Genentech; Research funding (Institution): Roche. V. Guarneri: Research funding (Institution): Roche. All other authors have declared no conflicts of interest.

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Proffered paper session - Breast cancer, early stage Proffered Paper session

187O - High-dose chemotherapy (HDCT) with hematopoietic stem cell transplantation (HSCT) in high-risk breast cancer (BC) patients with _4 involved axillary lymph nodes (ALN): 20-year follow-up of a randomized phase 3 study

Presentation Number
187O
Lecture Time
17:03 - 17:15
Speakers
  • Tessa G. Steenbruggen (Amsterdam, NL)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

Adjuvant HDCT for high-risk BC is not beneficial overall compared to conventional chemotherapy at the cost of considerable toxicity. HDCT benefit, however, may be present in very high-risk patients (i.e. >9 involved ALN) and in triple negative (TN) BC patients, although long-term results are lacking for most initial studies. We evaluated long-term outcome of a randomized phase 3 study, conducted from 1993 to 99.

Methods

Patients aged <56 years with early BC and ≥4 involved ALN were randomized to either conventional chemotherapy or HDCT as adjuvant systemic treatment. The conventional arm consisted of 5x fluorouracil, epirubicin and cyclophosphamide (FEC) 3-weekly. In the HDCT arm, the 5th FEC was replaced by cyclophosphamide 6000 mg/m2, thiotepa 480 mg/m2, carboplatin 1600 mg/m2 and supported with autologous HSCT (Rodenhuis, NEJM 2003). We collected 20-year follow-up data from medical records, general practitioners, and the Netherlands Cancer Registry. Endpoints were relapse free survival (RFS), overall survival (OS), BC specific survival (BCSS), and safety based on intention to treat analyses.

Results

885 patients (64% 4-9 ALN, 36% >9 ALN; 53% ER+/HER2-, 23% HER2+, 16% TN, 8% unknown) were randomized to FEC (n = 443) or HDCT (n = 442). The table shows efficacy results of univariable Cox models. With 20 years median follow-up, relapse or death occurred in 272 patients (61%) who received FEC vs in 257 (58%) HDCT patients (HR 0.88; 95% CI 0.74-1.05). The effect of HDCT compared to FEC was most pronounced in patients with >9 involved ALN and in TNBC patients. In 138 TNBC patients the 20-year OS estimate was 52% after HDCT vs 39% after FEC. Long-term safety and BCSS will also be presented at the meeting.

RFSHDCTFEC
N20 yr (%)95% CI20 yr (%)95% CIHR95% CIp
All8854237-473833-430.880.74-1.050.15
4-9 ALN5684338-504438-501.000.81-1.250.97
>9 ALN3173931-472721-360.710.54-0.940.02
ER+/HER2-4694034-473630-430.830.66-1.040.11
HER2+2053830-494233-521.150.80-1.630.46
TN1385140-653424-480.660.42-1.030.07
OSHDCTFEC
N20 yr (%)95% CI20 yr (%)95% CIHR95% CIp
All8854541-504137-460.890.74-1.060.18
4-9 ALN5684640-524842-541.010.81-1.270.91
>9 ALN3174437-533023-380.720.54-0.950.02
ER+/HER2-4694640-534034-470.810.64-1.030.09
HER2+2054032-514637-561.150.80-1.660.44
TN1385241-653929-520.710.45-1.120.14

Conclusions

Long-term follow-up confirms survival benefit of HDCT in BC patients with >9 involved ALN and suggests benefit in TNBC patients.

Clinical trial identification

NCT03087409.

Legal entity responsible for the study

High-risk breast cancer study group from the Netherlands Working Party on Autologous Transplantation in Solid Tumors.

Funding

Has not received any funding.

Disclosure

T.G. Steenbruggen: Financial support: Memidis Pharma unrelated to the submitted work. V.C.G. Tjan-Heijnen: Research funding through grants institution: Eisai, Roche, Pfizer, Novartis, and AstraZeneca; Compensation for service as a consultant: AstraZeneca, Pfizer, Novartis, and Roche; Honoraria: Pfizer, Roche, and Novartis; Travel expenses: Pfizer, Novartis, and Roche. S.C. Linn: Institutional research funding: AstraZeneca, Amgen, BMS, Genentech, Roche, and Sanofi; Advisory board member: AstraZeneca, Novartis, Roche and Sanofi. E.G.E. de Vries: Consulting/advisory board fees: Synthon, Pfizer and Sanofi; Grants: Novartis, Amgen, Roche/Genentech, Regeneron, Chugai, Synthon, AstraZeneca, Radius Health, CytomX Therapeutics and Nordic Nanovector, all to the hospital and unrelated to the submitted work. G.S. Sonke: Institutional research funding: AstraZeneca, Merck, Novartis, Roche, unrelated to the submitted work. All other authors have declared no conflicts of interest.

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Proffered paper session - Breast cancer, early stage Proffered Paper session

Invited Discussant one LBA TBC, 186O and 187O

Lecture Time
17:15 - 17:30
Speakers
  • Javier Cortes Castan (Barcelona, ES)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30