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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5278 - Actionable Mutations and Overall Survival in 3,211 Patients with Cancer: The Hellenic Cooperative Oncology Group Precision Medicine Initiative

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Elena Fountzila

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

E. Fountzila1, V. Kotoula2, G. Koliou2, E. Giannoulatou3, H. Gogas2, C. Papadimitriou2, I.S. Tikas2, K. Papadopoulou2, F. Zagouri2, C. Christodoulou2, A. Koutras2, E. Razis2, P. Papakostas2, E. Samantas2, G. Aravantinos2, A. Psyrri2, D.G. Pectasides2, A. Futreal4, A. Tsimberidou1, G. Fountzilas2

Author affiliations

  • 1 Department Of Investigational Cancer Therapeutics, MD Anderson Cancer Center, The Univesity of Texas, 77030 - Houston/US
  • 2 Data Office, Hellenic Cooperative Oncology Group (HeCOG), 11524 - Athens/GR
  • 3 Department Of Bioinformatics, Victor Chang Cardiac Research Institute, 2010 - Darlinghurst, NSW/AU
  • 4 Genomic Medicine, MD Anderson Cancer Center, 77030-4095 - Houston/US
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Resources

Abstract 5278

Background

We evaluated the impact of tumor type and molecular profiling on overall survival of patients (pts) with cancer referred to Medical Oncology Departments affiliated with the Hellenic Cooperative Oncology Group (HeCOG).

Methods

Pts referred from 1989 to 2017 had molecular testing (for research) of archival tumor tissue collected at the time of diagnosis (stage I-III, 82%; stage IV, 18%). Tumor-specific (e.g. breast, colon) gene panels (45-101 genes) were used to identify pathogenic mutations in clinically relevant genes. Deep sequencing was performed at the Laboratory of Molecular Oncology, Aristotle University of Thessaloniki and HeCOG. Mutation annotation was performed at MD Anderson Cancer Center. All pts received standard-of-care anticancer therapy.

Results

We analyzed 3,211 pts (median age, 58 years; men, 29%) with informative sequencing data. Results by tumor type and molecular pathway are shown in the table. Overall, 1,193 (37%) pts had ≥1 actionable alterations [115 (3.6%) ≥4]. The most common affected pathways were PI3K, RAF/MEK, homologous recombination repair (HRR), and tyrosine kinase; 294 (9.2%) pts had alterations in > 1 pathways. The median follow-up of alive patients is 7.48 years (yrs) (95%CI, 7.36-7.59). Of 3,211 pts, 1,060 (33.01%) have died. The median overall survival is 16.08 yrs (95%CI, 13.25-16.75). Of pts with breast cancer and actionable mutations, the 5-yr survival rates were: stage I-III (n = 501) 88.8%; stage IV (n = 14), 51.1% (p<.0001). Of pts with colorectal cancer and actionable alterations, the 5-yr survival rates were: stage I-III (n = 299), 76.5%; stage IV (n = 50), 15.2% (p<.0001).

Conclusions

Tumor sequencing revealed clinically relevant genomic mutations in several molecular pathways. Prospective clinical trials validating the clinical utility of tumor profiling are warranted.

Clinical trial identification

Legal entity responsible for the study

Hellenic Cooperative Oncology Group.

Funding

Hellenic Cooperative Oncology Group.

Editorial Acknowledgement

NA

Disclosure

All authors have declared no conflicts of interest.Table: 1876P

Total NN with actionable alterations%Overall Survival
Tumor typeMedian, Years (95% CI)5-yr OS, % (95% CI)
Breast1,96452727NR87.8 (85.0-90.7)
Colorectal53335967NR68.0 (63.2-73.2)
Pancreatic188123650.82 (.65-.98)-
Nasopharyngeal14477548.92 (6.68-NR)65.2 (54.7-77.7)
Brain13124184.54 (1.69-9.71)46.9 (29.9-73.6)
Gastric10111114.18 (1.04-NR)39.8 (17.8-88.9)
Biliary Tract802633ND
Ovarian7046663.24 (2.18-5.32)36.4 (24.7-53.5)
Total3,2111,1933713.23 (10.6-NR)68.6 (65.9-71.4)
PathwayTotal testedN with actionable alterations%
PI3K/AKT/mTOR3,2116362016.08 (13.23- NR)82.3 (79.3-85.4)
MEK/RAF3,211459146.4 (4.08-8.92)52.3 (47.7-57.3)
HRR3,21126087.84 (5.33-NR)56.8 (50.7-63.5)
Tyrosine kinase3,2111615NR69.2 (62.0-77.3)

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