Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Discussion 1 – Translational research

2434 - Prevalence and prognostic effect of high tumor mutation burden (TMB-H) across multiple less common solid cancers using a real-world dataset

Date

29 Sep 2019

Session

Poster Discussion 1 – Translational research

Presenters

Daniel Backenroth

Citation

Annals of Oncology (2019) 30 (suppl_5): v760-v796. 10.1093/annonc/mdz268

Authors

D. Backenroth1, C. Shao2, G. Li3, L. Huang2, S.K. Pruitt2, E. Castellanos1, G.M. Frampton3, K.R. Carson1, T. Snow1, G. Singal3, D. Fabrizio3, B.M. Alexander3, F.J. Jin2, W. Zhou2

Author affiliations

  • 1 Quantitative Sciences, Research Oncology And Life Sciences Partnerships, Flatiron Health Inc., 10013 - New York/US
  • 2 Merck Research Laboratories (mrl), Merck & Co., Inc., 07033 - Kenilworth/US
  • 3 Data Products, Cancer Genomics Research, Product Development And Clinical Development, Foundation Medicine, Inc., 02141 - Cambridge/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 2434

Background

Little is known about the prognostic effect of TMB-H among patients with less common cancers who did not receive an immunotherapy (IO).

Methods

The de-identified Flatiron Health-Foundation Medicine (FMI) Clinico-Genomic Database was used to select patients (pts) with any of 10 solid cancers (Table). 109 Pts with confirmed microsatellite instability-high (MSIH) cancers were excluded, of which 101 pts were endometrial cancer. TMB-H was defined as ≥ 10 mutations per megabase (Mut/Mb) with an additional analysis using a cutoff of 13 Mut/Mb. For overall survival (OS) analysis, Pts with IO were excluded if start of IO earlier than or equal to FMI report date (69 pts), or censored if start of IO later than FMI report date (243 pts). OS was analyzed using Kaplan-Meier method and Cox proportional hazard model, adjusting for age, gender, cancer types, practice type and albumin. A non-inferiority test of TMB-H having longer OS than TMB-low (-L) was carried out with a prespecified hazard ratio (HR) of 0.75.

Results

Of the 2,589 pts (table), average age at diagnosis was 64 years and 65% were female. Median TMB was 2.6 Mut/Mb overall, ranged from 1.7 (Meso, salivary, thyroid) to 8.7 (SCLC) Mut/Mb. Overall 12.8% were TMB-H with the highest in SCLC (40.0%) and lowest in meso (1.2%). The adjusted HR (AHR) of TMB-H vs. -L was 0.94 (95% CI: 0.77-1.13) for OS from FMI report date, which met the prespecified threshold for non-inferiority by rejecting the null hypothesis. The AHR was 0.84 (0.67-1.05) using alternative cutoff of 13 Mut/Mb. Comparable results were observed when including MSI-H pts and calculating OS from 1st observed antineoplastic treatment date.Table: 1877PD

NTMB-HOS (month, 95%CI)HRadjustPadjust
n%TMB-HTMB-L
Total2,58933212.88.4 (7.4; 11.4)10.5 (9.5; 11.5)0.94 (0.77; 1.13)0.491
SCLC30512240.06.4 (5.4; 7.5)7.4 (5.5; 10.5)1.03 (0.74; 1.44)0.863
Neuroendocrine1644829.310.4 (6.4; NA)6.4 (4.5; 10.5)0.83 (0.48; 1.44)0.506
Cervical1141714.9NA (6.4; NA)7.4 (4.4; 11.5)0.32 (0.08; 1.31)0.113
Anal1251713.67.4 (2.5; NA)7.5 (5.5; 15.4)0.84 (0.40; 1.79)0.659
Vulvar30413.38.5 (0.5; NA)6.5 (2.5; NA)1.18 (0.22; 6.29)0.848
Salivary1692213.04.5 (3.5; NA)15.5 (10.5; 21.5)1.20 (0.48; 2.99)0.691
Endometrial5906611.211.4 (8.5; 26.5)13.5 (11.5; 15.4)1.15 (0.75; 1.75)0.522
Biliary706284.011.5 (7.4; NA)8.4 (7.4; 10.4)0.65 (0.35; 1.19)0.162
Thyroid22362.710.2 (1.5; NA)27.5 (21.5; NA)1.64 (0.39; 6.96)0.502
Meso16321.2NA12.5 (8.5; 15.5)-0.997

Conclusions

There is a wide range of TMB among these cancers. Non-inferiority testing and HR estimates comparing OS for TMB-H (≥10 Mut/Mb) vs. -L did not support an effect of TMB on OS in the absence of IO for these cancers. Further research is needed to explore whether the prognostic effect of TMB varies by tumor type or threshold.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

D. Backenroth: Shareholder / Stockholder / Stock options, Full / Part-time employment: Flatiron Health Inc. C. Shao: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co. G. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. L. Huang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co.. S.K. Pruitt: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc.. E. Castellanos: Full / Part-time employment: Flatiron Health Inc.. G.M. Frampton: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. K.R. Carson: Full / Part-time employment: Flatiron Health Inc.. T. Snow: Full / Part-time employment: Flatiron Health Inc.. G. Singal: Full / Part-time employment: Foundation Medicine. D. Fabrizio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. B.M. Alexander: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. F.J. Jin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc.. W. Zhou: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc..

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.