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

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

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)

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)

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.   

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.

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!

ESMO 2016 News in Oncology: Lung Cancer

ESMO 2016. LBA8_PR. KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumour proportion score (TPS) ≥50%

M. Reck et al.

Results: From Sep 19, 2014, to Oct 29, 2015, 305 pts from 16 countries were randomized: 154 to pembro, 151 to chemo. After a median follow-up of 11.2 mo, 48% of pts remained on pembro, 10% remained on chemo, and 44% crossed over from chemo to pembro upon PD. With 189 events, pembro significantly prolonged PFS over chemo (HR 0.50, 95% CI 0.37-0.68, P < 0.001; median 10.3 mo vs 6.0 mo). With 108 deaths, pembro also significantly prolonged OS (HR 0.60, 95% CI 0.41-0.89, P = 0.005; 6-mo OS 80% vs 72%). Pembro was also associated with higher ORR (45% vs 28%), longer response duration (median NR vs 6.3 mo), and lower incidence of any-grade (73% vs 90%) and grade 3-5 (27% vs 53%) treatment-related AEs. 

Conclusions: Pembro demonstrated superior PFS and OS over platinum-based chemo in pts with advanced NSCLC of PD-L1 TPS ≥50%. Along with the lower rate of treatment-related AEs, these data suggest pembro may be the new standard of care for first-line therapy of PD-L1–expressing advanced NSCLC without treatable oncogenic aberrations.

CARE Faculty Perspective: This is a pivotal trial in the field of lung cancer. Pembrolizumab may become the new standard of care for first line therapy of advanced NSCLC.

ASCO 2016: News in Lung Cancer - Abstract 9001

News in Lung Cancer

ASCO 2015. Abstract 9001. Epidermal growth factor receptor (EGFR) genotyping of matched urine, plasma and tumor tissue from non-small cell lung cancer (NSCLC) patients (pts) treated with rociletinib
Heather A. Wakelee et al.

Results: Of 417 pts in the 500 and 625 mg BID dosing groups (data cut-off date: 18 Sept 2015; pts enrolled as of 1 July 2015), 331 of 417 were T790M+ by central tissue genotyping; 189 of 242 were T790M+ by plasma genotyping; and 136 of 169 were T790M+ by urine genotyping. Confirmed investigator-assessed objective response rate (ORR) and median duration of response (mDOR) were similar regardless of sample type. Four of 14 pts who were T790M+ in plasma but T790M− in tissue responded; 3 of 7 pts who were T790M+ in urine but T790M− in tissue responded. Shrinkage of target lesions correlated with higher T790M: activating mutation ratio in plasma (P=0.006). With tissue as reference, positive percent agreement for T790M status between matched plasma and tissue was 81.5% (n=195) and 83.8% (n=136) between matched urine and tissue. In both dosing groups, the most common treatment-related adverse events were hyperglycemia, diarrhea, nausea, and fatigue. 

Conclusions: In T790M+ pts, response was similar whether T790M status was identified by tissue, plasma or urine. Plasma and urine testing identified T790M mutations missed by biopsy due to tumor heterogeneity or inadequate sample quality. These data suggest plasma and urine EGFR analyses complement tissue biopsies in EGFR TKI resistant NSCLC. Clinical trial information: NCT01526928

CARE Faculty Perspective: This trial is revolutionary in terms of diagnosis. Diagnosing lung cancer can now be made easier by replacing lung biopsy in some instances with a test that identifies T790M or other known mutations using tissue, plasma or urine. One such test has just been released by the FDA, and we could expect it in Canadian centres in the future.