ESMO 2018: News in Oncology - Metastatic Breast Cancer

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290O - Patient-reported outcomes (PROs) in advanced breast cancer (ABC) treated with ribociclib + fulvestrant: results from MONALEESA-3

Peter A. Fasching (Erlangen, DE)

In the MONALEESA-3 trial (NCT02422615), ribociclib + fulvestrant significantly improved progression-free survival (PFS) vs placebo + fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative BC who had received no prior therapy or only 1 line of prior endocrine therapy for ABC.  This abstract presents PROs from the MONALEESA-3 trial including health-related quality of life (HRQoL).  According to the trial results, mean GHS/QLS (global health status/quality of life scale score of the EORTC QLQ-C30 questionnaire) was maintained or improved during every cycle of treatment in both arms.  Ribociclib + fluvestrant significantly prolonged PFS compared to placebo + fluvestrant while maintaining QoL.  

291O - Ribociclib (RIB) + tamoxifen (TAM) or a non-steroidal aromatase inhibitor (NSAI) in premenopausal patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC): MONALEESA-7 patient-reported outcomes (PROs)

Nadia Harbeck (Munich, DE)

In the Phase III MONALEESA-7 trial (NCT02278120), RIB + TAM/NSAI + goserelin (GOS) significantly improved progression-free survival vs placebo (PBO) + TAM/NSAI + GOS in premenopausal pts with HR+, HER2– ABC.  This abstract features PRO updates from the MONALEESA-7 trial.  According to PROs, RIB + TAM/NSAI + GOS improves HRQoL and maintains functioning, work productivity, and activity in premenopausal pts with HR+, HER2– ABC. RIB + TAM/NSAI + GOS is also associated with a clinically meaningful reduction in pain vs PBO + TAM/NSAI + GOS.

292O - Patient-reported outcomes (PRO) in patients (pts) with advanced breast cancer and a germline BRCA1/2 mutation (gBRCAm) receiving talazoparib (TALA) vs physician’s choice chemotherapy treatment (PCT): a focus on the EMBRACA triple negative (TNBC) subpopulation

Hope S. Rugo (San Francisco, US)

One of the key subgroup analyses of the EMBRACA trial (a randomized 2:1 open-label phase 3 study) revealed a statistically significant improvement in progression-free survival (PFS) with TALA vs PCT in pts with advanced TNBC and gBRCAm.  This abstract reports on a post hoc analysis of PROs from the EMBRACA trial. In pts with gBRCAm advanced TNBC, TALA resulted in significantly greater improvement from baseline and delayed TTD (time to deterioration) in GHS/QoL (global health status/quality of life) and pain symptoms vs PCT.

ESMO 2018: News in Oncology - Early Stage Breast Cancer

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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

Claire Hulme (Leeds, GB) and Peter Hall (Edinburgh, GB)

Adjuvant trastuzumab has significantly improved outcomes for HER2+ EBC, using the 12m (month) duration empirically adopted from pivotal registration trials. Given the annual per patient cost of trastuzumab treatment, a shorter duration has the potential to improve cost-effectiveness if efficacy is maintained.  According to results from the PERSEPHONE trial, 6m of trastuzumab treatment was shown to be cost effective compared to 12m of trastuzumab treatment with no evidence of a detriment to quality of life. 

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

Barbara Pistilli (Villejuif, FR)

Previous studies have demonstrated that younger patients (pts) with breast cancer (BC) are more likely to be non-adherent to adjuvant ET, leading to impaired prognosis.  According to the results of this CANTO cohort study, at one year from initiation of TAM (tamoxifen), 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.

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

Maria Vittoria Dieci (Padova, IT)

TILs are an established prognostic factor for triple negative breast cancer and the ShortHER trial investigated the prognostic role of TILs for HER2+ early breast cancer patients.  According to the trial results, TILs are an independent prognostic factor for HER2+ early breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Integration of TILs in prognostic algorithms could help refine risk stratification and guide therapeutic de-escalation.

Press Release: CARE Congress on Biosimilars

On January 13th, 2017 CARE faculty specialists representing the fields of gastroenterology, hematology, oncology, respirology and rheumatology met to consider the integration of Biosimilars into the Canadian healthcare system.

Biosimilars are drugs that may replace expensive biologic drugs that are going off patent.  With biosimilars being relatively new to the Canadian landscape, there are also a number of questions/considerations on extrapolating data, interchangeability, immunogenicity, and systemic challenges (tracking and monitoring) that require attention.

Recognizing both the potential impact on the Canadian healthcare system and the importance of involving stakeholders, CARE faculty invited 16 speakers representing Canadian researchers, clinicians, Health Canada, public and private funding agencies, health economists, hospital pharmacists, nurses, advocacy groups, ethicists and legal experts to share perspectives, concerns, wants and needs.

An audience of 100+, representing the above named stakeholders, along with various levels of government, pharmaceutical companies and industry associations, listened in while speakers and assembled faculty discussed biosimilars from multiple perspectives.

The aim of this Congress is to increase collective understanding, consider education needs for specialists and assembled stakeholders, and ultimately refine a CARE guidance/position on Biosimilars.


CARE Faculty believes: 

  • Developing clinical practice through optimization of current therapies
  • Improving patient outcomes by developing innovative therapeutics
  • Ensuring access to quality care for all Canadians by the responsible and evidence-based use of treatment
  • Competition is welcomed to improve efficiency and access


CARE™ funding sources:

CARE™ receives unrestricted funding from multi-industry sponsors, institutions and associations. Content reflects the opinions, presentations and analyses of experts, investigators, educators and clinicians ("CARE Faculty"), whose activities, while independent, are commercially supported by the noted sponsor(s). Program content is developed independently of sponsor(s).


Background Steps that led up to this CARE™ Congress

  • CARE™ conducted needs assessments in oncology, hematology, rheumatology, and gastroenterology to understand current perceptions of biosimilars and their use in Canada
  • A multi-disciplinary group of CARE faculty members met October 27th, 2016 to discuss the various needs assessment data, and the impact biosimilars will have in Canada
  • There was consensus to host a larger meeting involving more stakeholders; CARE™ has worked to quickly assemble this Congress involving not only different specialties, but different stakeholder representatives.

For more information on the steering faculty, assembled CARE faculty, speaker list, or for questions/information needs regarding CARE, please contact Christina Lopes or Erica Duncan. 



  1. Hirsch BR, Lyman GH. Biosimilars: are they ready for primetime in the United States? J Natl Compr Canc Netw. 2011;9: 934–943
  2. Based on 2013 sales of biologics with patents expiring before 2021 (Remicade, Eprex, Aranesp, Levemir, Humira, Avastin, Enbrel, Lucentis, Rituxan, Gonal-F). IMS Health Canada - Canadian Drug and Hospital (CDH) Sales, December 2013, page 11

Click here to view more highlights from the CARE Congress on Biosimilars.

SABCS News in Breast Cancer: Neoadjuvant Therapy (Canadian Context)

SABCS 2016. P5-16-17. Population based long-term outcomes of pathologic complete response after neoadjuvant chemotherapy in stage I-III breast cancer: The British Columbia experience

Sun J, Lovedeep G, Diocee R, Speers C, Lohrisch C and Chia S.

Results: 267 pts who met inclusion criteria were identified, of whom 5% had stage I, 33% Stage II and 59% Stage III breast cancer. Median follow up was 7.4 years. Overall 74 pts (28%) demonstrated a pCR and 193 pts did not. pCR pts had better 5-yr overall survival (OS) vs. non-pCR pts: 88% vs. 73% (HR 0.43, 95% CI 0.23-0.82, p=0.01). 5-yr disease free survival (DFS) was 84% in pCR pts vs. 70% in non-pCR pts (HR 0.45, 95% CI 0.24-0.83, p=0.01). Similarly, 5-yr breast cancer specific survival (BCSS) and distant disease free survival (DDFS) were significantly better in favor of the pCR cohort: HR 0.39 (95% CI 0.18-0.82, p=0.01) and HR 0.45 (95% CI 0.24-0.83, p=0.02) respectively. pCR pts were more likely to be HER2-positive and/or ER negative.

Conclusions: Our population based results showed that early stage breast cancer pts who achieved pCR after neoadjuvant chemotherapy had better outcomes on all survival parameters compared to pts who did not achieve a pCR. This finding is consistent with results from neoadjuvant clinical trials and the FDA meta-analysis. These 'real world' results demonstrate that pCR can be used as a surrogate endpoint for survival outcomes even among non-trial pts.

CARE Faculty Perspective: Though controversy continues as to the applicability of pCR as a surrogate for long-term clinical outcomes, much of that pertains to trial participation relative to ‘real world’ experience. This population based experience from British Columbia supports that pCR is a surrogate, and most impressively the hazard ratio for DFS was almost identical to the FDA meta-analysis for EFS (HR 0.48). Most regulatory authorities (FDA and EMEA) have embraced this association, and it is now time for the Canadian counterpart and review guidance panels to also accept the correlation so that new therapeutic agents with demonstrated benefit in both advanced stage and pre-operative stage trial settings can reach all suitable and eligible patients sooner rather than later.

SABCS News in Breast Cancer: Locally Advanced/Metastatic Disease

SABCS 2016. P4-22-13. Everolimus plus trastuzumab and paclitaxel as first-line therapy in women with HER2+ advanced breast cancer: Overall survival results from BOLERO-1

Yardley D, Hurvitz S, Jiang Z-f, Toi M, Burris H, Buyse M, Slamon D, Makhson A, Elsaid A, Lerzo G, Hellerstedt B, Nuzzo F, Sohn J, Manzyuk L, Cabaribere D, Lincy J, Weimann A, Noel-Baron F, Pacaud L, Andre F
Results: At data cutoff (Dec 31, 2015), the median duration of exposure was 40.8 weeks (range: 0.6-320.4) in the EVE arm and 48.1 weeks (range: 1.1-308.0) in the PBO arm. After a median follow-up of 60.3 mo, 350 deaths were recorded in the full population, 238 (49.6%) in the EVE arm and 112 (46.9%) pts in the PBO arm. In the full population, the median OS was comparable in the EVE vs PBO arms (48.6 mo vs 50.0 mo respectively; HR = 1.13; 95% CI: 0.90-1.42). In the HR- subpopulation, 138 deaths were recorded; 88 (42.3%) pts in the EVE arm and 50 (48.5%) pts in the PBO arm. In the HR- subpopulation, the median OS in the EVE arm was longer compared to PBO arm (57.0 mo vs 41.6 mo respectively; HR = 0.83; 95% CI: 0.59-1.18). Stomatitis, diarrhea, alopecia, cough, rash, pyrexia, neutropenia, and fatigue were the most frequent adverse events (AEs) reported in EVE arm (≥35%). AEs leading to dose interruption and/or change were reported in 441 (93.4%) pts in EVE arm and 165 (69.3%) pts in the PBO arm respectively. Overall, AEs leading to treatment discontinuation were reported in 262 (55.5%) pts in EVE arm and 98 (41.2%) pts in PBO arm. Serious AEs were reported in 171 (36.2%) pts in the EVE arm and 40 (16.8%) pts in the PBO arm respectively. On treatment AE related deaths were reported for 3.6% pts in the EVE arm and 0% pts in the PBO arm.

Conclusions: The median OS was similar in the EVE vs PBO arms for overall population. However, a prolongation of 15.4 mo in median OS of HR- subpopulation was observed in the EVE arm vs PBO arm in this exploratory analysis. Pts in the EVE arm had a manageable safety, consistent with the safety profile of EVE and no new safety signals were identified.

 CARE Faculty Perspective: The addition of everolimus, a mTOR inhibitor, to paclitaxel and trastuzumab did not significantly improve PFS in women with metastatic HER-2 + breast cancer (BOLERO-1: 15.0 vs 14.5 months). Overall survival was an exploratory endpoint for this study. At a median follow-up of 60 months, there was no statistically significant difference in median OS (48.6 vs 50 months; HR = 1.13) although women with HR – metastatic breast cancer appeared to benefit from the addition of everolimus (median OS 57 vs 41.6 months; NS) to paclitaxel/trastuzumab. More toxicity (e.g.  stomatitis, diarrhea, rash) was reported in the combination arm. These results do not support the addition of everolimus to standard therapy in this patient population. Prospective studies are needed to explore any potential benefit from the addition of everolimus to standard therapy in women with HER2 +, HR- disease.


Related Abstract of Interest:

SABCS 2016. P6-16-03. Phase 2 trial of everolimus and/or trastuzumab in hormone refractory, hormone receptor (HR)-positive, HER2-normal metastatic breast cancer (MBC)
Paplomata E et al.

SABCS News in Breast Cancer: Adjuvant Therapy

SABCS 2016. S1-03. First results from the multicenter phase III DATA study comparing 3 versus 6 years of anastrozole after 2-3 years of tamoxifen in postmenopausal women with hormone receptor-positive early breast cancer

Tjan-Heijnen VC, Van Hellemond IE, Peer PG, Swinkels AC, Smorenburg CH, Van der Sangen M, Kroep JR, De Graaf H, Honkoop AH, Erdkamp F, Van den Berkmortel FW, Kitzen JJ, De Boer M, De Roos WK, Linn SC, Imholz AL, Seynaeve C.

Results: Patients were randomized from July 2006 till August 2009. Three years after randomization 1663 patients had no DFS events, with an equal distribution between the treatment arms. The patient and tumor characteristics were well balanced. The median age at randomization was 57 years (P5 = 45 years, P95 = 76 years), the median primary tumor size was 21 mm (P5 = 10 mm, P95 = 50 mm), 67% of the patients had node-positive disease, and in 2% the tumor was HER2-positive (14% unknown); 64% of the patients had received adjuvant chemotherapy and <1% adjuvant trastuzumab. The median adapted follow-up was 4.1 years (P5 = 2.9 years, P95 = 5.8 years). No unexpected safety issues were seen. The 5-year ADFS was 79% in the 3-year and 83% in the 6-year anastrozole treatment group, yielding a HR for ADFS-event of 0.78 (95% CI 0.61 to 1.00; p = 0.0528). In patients with node-positive disease (N = 1117), the HR for ADFS-event was 0.71 (95% CI 0.53 to 0.96; p=0.0232), in N0 disease (N=546) 1.01 (95% CI 0.62 to 1.63; p=0.9817) and in patients with both ER and PR positive breast cancer (N = 1264) 0.68 (95% CI 0.51 to 0.90; p=0.0072). The 5-year adapted overall survival was not different between the treatment groups.

Conclusion: These findings do not yet support the use of extended adjuvant AI prescription after 5 years of sequential endocrine therapy for postmenopausal patients with hormone receptor-positive breast cancer, but suggest benefit for a selected group of patients. Continued follow-up is needed to assess long-term efficacy and safety.

CARE Faculty Perspective: The DATA study is similar in design to the NCIC MA.17 trial of an AI (anastrazole) after a defined duration of tamoxifen (2-3 years). The difference being MA.17 had 4.5 – 6 years of tamoxifen followed by 5 years of letrozole vs placebo. Remembering that after a median of 2.4 years of study treatment the study (MA.17) was un-blinded in favor of letrozole. There has lingered a debate whether a full 5 years of letrozole was sufficiently warranted relative to 2.5 years. The DATA study is also attempting to answer a clinically relevant question for those patients treated with the switch strategy (TAM-AI), whether extending the duration of an AI beyond the 5 years of total hormonal therapy provides additional efficacy. The study was powered (80%) to detect an increase in 3 year aDFS from 90% to 94% (HR 0.60). The study did NOT meet its primary endpoint of 3 year aDFS. Furthermore, there is no difference in OS. However, it can be argued that the follow up is perhaps too short in a luminal breast cancer population. One should be cautious to over-interpret subgroup analyses, for the forest plots are only univariate analyses. At present, it is NOT standard of care to extend an AI beyond the 5 years of total hormonal therapy. However, until a predictive assay is validated, we may consider in individual cases of significant ‘high risk’ disease to have a discussion regarding the pros and cons and the limitations of the DATA study.

Insights on the NOR-SWITCH trial are now available! Hear from Canadian experts Drs. Brian Feagan & John Marshall

Biologic therapy has revolutionized the treatment of IBD and improved patient outcomes drastically. Many of the biologic therapies we routinely use are now or soon going off patent and competitive molecules, subsequent entry biologics (SEBs), are now being introduced. SEBs have potential implications for our own practices but also for how we manage our pharmacy budgets and how we deliver health care in Canada.

The NOR-SWITCH trial was a randomized, open-label trial studying a cohort of patients who were stable or in remission on the innovator biologic, infliximab (REMICADE®). Patients were randomized to either continue with infliximab or switch to a SEB version of infliximab (INFLECTRA® in Canada). This was a cross specialty trial that included patients from a variety of diagnoses, including: rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, UC, CD and chronic plaque psoriasis. Each group was followed for different endpoints over the course of the trial.

CARE Gastroenterology Faculty lead, John Marshall (McMaster University), sat down with Dr. Brian Feagan (Professor of Medicine at the University of Western) to critically assess this study and discuss how the results should be interpreted and applied in Canadian practice.


Interested in learning more? Join us at The CARE Congress on Biosimilars!