M. Dieci (Padova, Italy)
IOV - Istituto Oncologico Veneto IRCCSAuthor Of 3 Presentations
Should all breast cancer patients receiving AI be treated with bone-modifying agents regardless of age and baseline T-score? NO (ID 311)
4MO_PR - HER2-low breast cancer: evolution from primary breast cancer to relapse. (ID 268)
Abstract
Background
About a half of breast cancers traditionally classified as HER2-negative show a low HER2 expression (IHC 1+ or IHC 2+ and ISH negative) that can be targeted by new antibody-drug conjugates. There is no data on the evolution of HER2-low status from primary tumor to relapse.
Methods
Patients with matched primary and relapsed breast cancer samples from two Institutions (IOV-IRCCS Padova and Treviso Hospital) were included. HER2 was evaluated according to ASCO/CAP recommendations in place at the time of diagnosis. Cases diagnosed between 2007 and 2013 were reviewed by IHC to comply with the cut-off of >10% cells staining for HER2 positivity. Moreover, 100 random samples were reviewed by a blinded pathologist: agreement with the original report was 80%. HER2-neg cases were sub-classified as HER2-low (IHC 1+, or IHC 2+ and ISH not amplified), or HER2-0 (IHC 0).
Results
575 patients were included. Primary tumor phenotype was: 59% luminal-like (HR+/HER2-neg), 25% HER2-pos, 16% triple-negative. The proportion of HER2-low cases was 34% on the primary tumor and 38% on the relapse samples. Among HER2-neg cases, HER2-low status was more frequent in Luminal-like vs triple-negative tumors (47% vs 41% on primary tumor samples, p=0.268; 54% vs 40% on relapse samples, p=0.006). The overall rate of HER2 discordance was 38% (Table), mostly represented by HER2-0 switching to HER2-low (15%) and HER2-low switching to HER2-0 (14%). A minority (9%) of cases lost or acquired HER2-positivity. Among patients with a primary HER2-neg tumor, the rate of HER2 discordance was higher in luminal-like vs triple-negative cases (45% vs 35% p=0.080). This difference was mostly driven by cases switching from HER2-0 to HER2-low: 40% of luminal-like/HER2-0 vs 24% of triple-negative/HER2-0 patients (p=0.088).
Relapse HER2-0 HER2-low HER2-positive Total Primary tumour n % n % n % n % HER2-0 134 23% 85 15% 13 2% 232 40% HER2-low 78 14% 109 19% 9 2% 196 34% HER2-positive 6 1% 23 4% 118 20% 147 26% Total 217 38% 218 38% 140 24% 575 100%
Conclusions
HER2-low expression is highly unstable during disease evolution. Relapse biopsy in case of a primary HER2-0 tumor may open new opportunities for treatment in a relevant proportion of patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Fassan: Advisory/Consultancy, Research grant/Funding (institution), outside the submitted work: Astellas Pharma; Advisory/Consultancy, outside the submitted work: Diaceutics; Advisory/Consultancy, outside the submitted work: Tesaro; Research grant/Funding (institution), outside the submitted work: QED Therapeutics. P.F. Conte: Research grant/Funding (institution), outside the submitted work: Merck; Honoraria (self), Research grant/Funding (institution), outside the submitted work: Roche; Honoraria (self), outside the submitted work: Novartis; Honoraria (self), outside the submitted work: Lilly. V. Guarneri: Honoraria (self), Research grant/Funding (institution), outside the submitted work: Roche; Honoraria (self), outside the submitted work: Novartis; Honoraria (self), outside the submitted work: Eli Lilly. M.V. Dieci: Honoraria (self), outside the submitted work: Genomic Health; Honoraria (self), outside the submitted work: Eli Lilly; Honoraria (self), outside the submitted work: Celgene. All other authors have declared no conflicts of interest.
41O - Nine weeks vs 1 year adjuvant trastuzumab: long term outcomes of the ShortHER randomised trial. (ID 233)
Abstract
Background
The ShortHER trial randomised 1254 patients with HER2+ early breast cancer to chemotherapy plus 9 weeks vs 1 year adjuvant trastuzumab. The study was designed as a non inferiority trial with a DFS hazard ratio (HR) < 1.29 as the non inferiority margin. At the event driven analysis, the HR for DFS was 1.13 (90% CI 0.89-1.42) therefore non inferiority could not be claimed (P Conte et al, Ann Oncol 29:2328-2333). Here we report the overall survival (co-primary end point of the study) and the updated DFS curves according to risk categories of long vs short treatment arms.
Methods
Study design, patient characteristics and event-driven DFS analysis have been previoulsy reported. This analysis reports the overall survival and the updated DFS curves according to HR status and three risk categories: low risk (pT< 2cm and pN0), intermediate risk (pT < 2cm and 1-3 pN+ or pT > 2cm and 0-3 pN+) and high risk (any pT and 4+ pN+).
Results
At a median follow up of 8.7 years, 237 DFS events have occurred: 121 in the short and 116 in the long arm respectively (HR 1.09; 90% CI 0.88-1.35). DFS according to post-hoc risk groups are: low risk (37.2% of the study population) HR 0.91 (90% CI 0.60-1.38); intermediate risk (46.7% of the study population) HR 0.88 (90% CI 0.63-1.21); high risk (15.2% of the study population) HR 2.06 (90% CI 1.36-3.13). DFS according to HR status are: HR+ HR 1.11 (90% CI 0.85-1.46); HR- HR 1.06 (90% CI 0.75-1.50). 109 deaths have been reported (58 in the short, 51 in the long arm). The 9 yrs OS is 90% in the short and 91% in the long arm (HR 1.18; 90% CI 0.86-1.62).
Conclusions
The updated DFS and OS analysis of the ShortHER trial confirm the favourable long-term results of 9 weeks adjuvant trastuzumab in the patients with low and intermediate risk factors. These patients represent 83.9 % of the ShortHER study population and the majority of the patients treated in daily practice. One-year trastuzumab remains standard. On the basis of these results however, a shorter trastuzumab administration could be an option in case of limited access to trastuzumab. Our data are reassuring for patients who have to discontinue trastuzumab due to a decline in LVEF.
Clinical trial identification
EUDRACT number: 2007-004326-25; NCI number: NCT00629278.
Legal entity responsible for the study
University of Padua, University of Modena and Reggio Emilia.
Funding
AIFA Agenzia Italiana del Farmaco (grant number FARM62MC97).
Disclosure
P.F. Conte: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): roche; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Merck kga; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Speaker Bureau/Expert testimony: Lilly. A. Frassoldati: Advisory/Consultancy, Travel/Accommodation/Expenses: roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Daiichi; Advisory/Consultancy: astrazeneca; Travel/Accommodation/Expenses: Lilly; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. O. Garrone: Advisory/Consultancy: Eisai; Advisory/Consultancy: Eli Lilly; Speaker Bureau/Expert testimony: Novartis. L. Cavanna: Speaker Bureau/Expert testimony: AstraZeneca; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Ibsen; Speaker Bureau/Expert testimony: Pfizer. A. Musolino: Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Macrogenics; Honoraria (self): Merck; Honoraria (self), Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Pfizer. A. Ferro: Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Eli Lilly. C. Zamagni: Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: PharmaMar; Advisory/Consultancy: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Honoraria (self): Quintiles MS; Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy: Gentili; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Array Biopharma; Research grant/Funding (institution): morphotek; Research grant/Funding (institution): synthon; Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy: Celgene. M.V. Dieci: Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy: Celgene; Advisory/Consultancy: Genomic Health. V. Guarneri: Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. All other authors have declared no conflicts of interest.
Presenter Of 1 Presentation
Should all breast cancer patients receiving AI be treated with bone-modifying agents regardless of age and baseline T-score? NO (ID 311)
Author Of 1 Presentation
- M. Bottosso (Padova, Italy)
- T. Giarratano (Padova, Italy)
- C. Barbieri (Padova, Italy)
- A. Menichetti (Padova, Italy)
- E. Cumerlato (Padova, Italy)
- F. Miglietta (Padova, Italy)
- E. Genovesi (Padova, Italy)
- O. Amato (Padova, Italy)
- M. Dieci (Padova, Italy)
- G. Griguolo (Padova, Italy)
- V. Guarneri (Padova, Italy)
122P - Abemaciclib in HR+/HER2- metastatic breast cancer: a real-world experience
Abstract
Background
Abemaciclib is approved for HR+/HER2- metastatic breast cancer in combination with endocrine therapy (ET). We evaluated safety and efficacy of abemaciclib in association with ET in a single-institution cohort.
Methods
Patients with HR+/HER2- metastatic breast cancer treated with abemaciclib in combination with ET as first or second line between April 2019 and November 2020 at Istituto Oncologico Veneto of Padova were identified. Clinicopathological characteristics, adverse events and their grade (according to CTCAE 5.0 criteria) were collected. Objective response rate (ORR) according to RECIST 1.1 was also evaluated.
Results
72 patients were included: 52 received abemaciclib as first line, 20 as second line; in 49 patients abemaciclib was administer in combination with an aromatase inhibitor, in 23 with fulvestrant. 95.8% of patients experienced at least one adverse event. The most common was diarrhea (79.2%), mainly G1 (66.7% of cases). Other common toxicities were: neutropenia (56.9%), increased serum creatinine (38.9%), anemia (37.5%), nausea (34.7%), fatigue (23.6%) and hypertransaminasemia (22.2%). Toxicities were mainly low grade; 10.1% of adverse events where G3-4. 48.6% of patients required a temporary interruption of abemaciclib and 45.8% a dose reduction. All 17 patients aged ≥70 required a dose reduction. A concomitant palliative radiotherapy was administered in 16 patients: in all cases radiotherapy was regularly completed; a temporary interruption of abemaciclib was required in 3 patients due to hematologic toxicities. In patients with measurable disease, ORR was 55.7%, significantly higher in first line compared to second line (70.5% vs 17.7%, p<0.001). ORR was not significantly different between full and reduced dose (46.9% vs 65.5%, p=0.143). At the time of the present analysis, 51 patients are still on therapy. Treatment discontinuations were due to disease progression in 17 patients, and to adverse events in 4 (G3 increased ALT in 1 patient and persistent G2-3 cutaneous toxicity in 3 patients).
Conclusions
In a real-world population, abemaciclib was associated with a meaningful rate of objective response, with a favourable safety profile. Side effects were mostly low grade, manageable with temporary interruptions or dose reductions.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M.V. Dieci: Honoraria (self): Eli Lilly; Honoraria (self): Genomic Health; Honoraria (self): Novartis; Honoraria (self): Celgene. G. Griguolo: Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Daiichi Sankyo. V. Guarneri: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Eli Lilly; Honoraria (self): MSD. All other authors have declared no conflicts of interest.