ESMO 2018: News in Oncology - Ovarian Cancer

ESMO 2018_Postcard Header .jpg

LBA36 - Association of PD-L1 expression and gene expression profiling with clinical response to pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase 2 KEYNOTE-100 study

Speaker:
Jonathan A. Ledermann (London, GB)

Results from the KEYNOTE-100 trial (NCT02674061) suggest that pembrolizumab (pembro) has clinical activity in patients (pts) with advanced ovarian cancer (AOC), and also suggests that PD-L1 expression (combined positive score [CPS] ≥10) was associated with response. This abstract explored other biomarkers that could be associated with response. In addition to PD-L1 CPS, T-cell-GEP (T-cell-inflamed 18-gene expression profile) was associated with a response to pembro monotherapy for treatment of AOC in a single-arm setting, while HRD (homologous recombination deficiency) biomarkers (like HRD genomic scar and BRCA 1/2 mutations) were not found to be associated with response.

937PD - A phase 2 trial of combination nivolumab and bevacizumab in recurrent ovarian cancer

Speaker:
Joyce F. Liu (Boston, US)

Single agent trials of immune checkpoint inhibitors that target PD1 or PDL1 have shown modest effect in ovarian Cancer.  VEGF (vascular endothelial growth factor) has demonstrated immune-suppressive functions through mechanisms such as impairment of dendritic cell function and maturation. As a result, anti-VEGF therapy may enhance immunotherapeutic responses when combined with immune checkpoint inhibitors. This abstract presents results from a trial to investigate the combination of the anti-VEGF agent bevacizumab and the PD1 inhibitor nivolumab in women with recurrent ovarian cancer.  Combination nivolumab + bevacizumab demonstrated clinical activity in women with recurrent ovarian cancer, with an overall confirmed response rate of 21% and a median PFS of 9.4 months. Further studies of anti-angiogenic and immune checkpoint blockade combinations in ovarian cancer are warranted.

LBA35 - TROPHIMMUN, a 2 cohort phase II trial of the anti-PD-L1 monoclonal antibody avelumab in chemo-resistant gestational trophoblastic neoplasia (GTN) patients: preliminary outcomes in cohort A

Speaker:
Benoit M. You (Lyon, FR)

PD-L1 is constitutively expressed in all GTN subtypes (Bolze et al. Int J Gynecol Cancer 2017).  The objective of the TROPHIMMUN trial is to assess the efficacy of the anti-PD-L1 monoclonal antibody avelumab in patients with chemoresistant GTN.  Preliminary TROPHIMMUN trial outcomes suggest that avelumab might be effective, and better tolerated than standard chemotherapy in patients with resistance to single chemotherapy. This is the first clinical trial reporting potential cures with a non-chemotherapy agent in patients with this rare cancer.

ESMO 2018: News in Oncology - Metastatic Breast Cancer

ESMO 2018_Postcard Header .jpg

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

Speaker:
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)

Speaker:
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

Speaker:
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

ESMO 2018_Postcard Header .jpg

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

Speakers:
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

Speaker:
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

Speaker:
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.

ESMO 2018: News in Oncology - Metastatic Non-Small Cell Lung Cancer (NSCLC)

ESMO 2018_Postcard Header .jpg

LBA50 - Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study

Speaker:
Suresh S. Ramalingam (Atlanta, US)

In the phase 3 FLAURA study, osimertinib showed efficacy in patients (pts) with previously untreated EGFRm (epidermal growth factor receptor mutant) advanced NSCLC compared to standard of care (SoC).  This abstract reports on the mechanisms of acquired resistance to osimertinib experienced by pts who progressed on the FLAURA study. In line with previous analyses, T790M was acquired in approximately 50% of SoC-treated pts, and none of the osimertinib‑treated pts; no unexpected resistance mechanisms were observed in osimertinib-treated pts. Exploration into novel acquired mutations is ongoing.

LBA52 - Results of the GEOMETRY mono-1 phase II study for evaluation of the MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated advanced non-small cell lung cancer (NSCLC)

Speaker:
Juergen Wolf (Cologne, DE)

MET mutations leading to exon 14 deletion (METΔex14) occur in 3-4% of NSCLCs.  Capmatinib is a highly potent and selective MET inhibitor and GEOMETRY mono-1 is a multi-cohort, multicenter study (NCT02414139), evaluating capmatinib in pts with METΔex14 mutated or MET amplified advanced NSCLC. In this study, Capmatinib has demonstrated a clinically meaningful response rate and a manageable toxicity profile in pts with METΔex14 mutated NSCLC, particularly in treatment naive pts where the ORR by BIRC (blinded imaging review committee) is 72%.

1377O - Phase 2 study of tepotinib + gefitinib (TEP+GEF) in MET-positive (MET+)/epidermal growth factor receptor (EGFR)-mutant (MT) non-small cell lung cancer (NSCLC)

Speaker:
Yi-Long Wu (Guangzhou, CN)

Patients with NSCLC can acquire resistance to EGFR tyrosine kinase inhibitors (EGFR TKIs) via MET activation, therefore dual MET/EGFR inhibition may have potential in EGFR TKI-resistant NSCLC. Tepotinib (TEP) is a potent, selective MET TKI and gefitinib (GEF) is an EGFR inhibitor. According to the results of this phase 2 study, the tepotinib + gefitinib combination (TEP+GEF) shows promising antitumor activity in pts with MET protein overexpression (IHC3+) and gene amplification EGFR-MT NSCLC.  TEP + GEF was well-tolerated in this study.   

ESMO 2018: News in Oncology - Sarcoma

ESMO 2018_Postcard Header .jpg

LBA67 - Cabozantinib in patients with advanced osteosarcomas and Ewing sarcomas: a French Sarcoma Group (FSG)/ US National Cancer Institute phase II collaborative study

Speaker:
Antoine Italiano (Bordeaux, FR)

Patients with relapsed and unresectable high-grade osteosarcoma (OS) and Ewing sarcoma (ES) have had a dismal and unchanging prognosis over the last decades.  There are currently no approved drugs for this challenging setting but pharmacologic inhibition of MET signaling and of aberrant angiogenesis has shown promise in pre-clinical OS and ES models.  This late-breaking abstract suggests that carbozantinib has shown meaningful clinical activity in OS and ES patients with heavily pre-treated advanced disease and reached the primary efficacy endpoints in both the OS and ES cohorts. 

1603O - Initial results of phase 1 study of DCC-2618, a broad-spectrum KIT and PDGFRa inhibitor, in patients (pts) with gastrointestinal stromal tumor (GIST) by number of prior regimens

Speaker:
Suzanne George (Boston, US)

DCC-2618 is a switch control inhibitor which broadly inhibits mutations in the KIT exons 9,11,13, 14, 17 and 18.  Results presented at ESMO 2018 suggest that DCC-2618 demonstrated encouraging clinical benefit and a favorable tolerability profile in GIST pts treated in the 2nd line or later.  Initiation of a second Phase 3 study for this agent in 2nd line GIST pts is anticipated by the end of 2018.

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. 

 


References:

  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.

ACR 2016 News in Rheumatology: Psoriatic Arthritis

ACR 2016. Abstract 1657. Soluble Biomarkers May Differentiate Psoriatic Arthritis from Osteoarthritis

Vinod Chandran et al.

Results: Univariate analyses revealed the following markers significantly differed across groups (p<0.001): COMP, hyaluronan; resistin, HGF, insulin, leptin; CRP, IL -6, -8, TNF-α, MCP-1, NGF. When comparing PsA to OA controlling for age and sex, the following markers significantly differed (p<0.001): COMP ; resistin, HGF, insulin; IL-6, -8, TNF-α, MCP-1, NGF; and Adipsin (p<0.03). Multivariate analysis demonstrated that COMP (OR 1.24, 95% CI 1.06, 1.46), resistin (OR 1.26, 95% CI 1.07, 1.48), MCP-1 (OR 1.28, 95% CI 1.01, 1.48) and NGF (OR <0.001, 95% CI <0.001, 0.25) were independently associated with PsA vs. OA. The area under the ROC curve (AUROC) for this model was 0.99. Internal cross-validation of the model consistently identified MCP-1 as a PsA marker. Further validation of the model including COMP, resistin, MCP-1 and NGF in an independent sample set showed an AUROC of 0.98 (Figure).  

Conclusion: A panel of 4 biomarkers (COMP, resistin, MCP-1, NGF) may distinguish PsA from OA. Clinical utility of these markers will need to be determined in prospective studies.              

CARE Faculty Perspective: One of the challenges in diagnosing psoriatic arthritis is differentiating it from osteoarthritis, especially erosive hand osteoarthritis. This early proof-of-concept study indicates that a panel of soluble biomarkers may be useful in making the diagnosis. These markers will now need to be further verified and validated as well as clinical utility and cost-effectiveness determined.