Abstract 110P
Background
RET alterations are oncogenic drivers in multiple solid tumours and can be targeted with effective and well tolerated RETis. The genomic landscape and natural history of pts whose tumours harbour RET fusions is unknown. We describe the clinical and demographic profiles of pts with RET-fp metastatic solid tumours receiving non-RETi therapy in a real-world setting and assess the value of RET fusions as prognostic biomarkers.
Methods
Demographics and clinical data for RETi-naïve pts with metastatic solid tumours (excluding non-small cell lung cancer) and ≥1 DNA Foundation Medicine NGS test (1 Jan 2012 – 31 Dec 2021) were obtained from the nationwide de-identified Flatiron Health and Foundation Medicine multi-tumour clinicogenomic database (CGDB). The overall survival (OS) of RET-fp pts was compared with that of matched RET-WT pts. Mahalanobis distance matching (two models) was used to match RET-WT pts with RET-fp pts 4:1, using preselected covariates. Model 1: pts matched based on age, gender, race, practice type, tumour type and ECOG PS. Model 2: pts matched based on all Model 1 covariates, plus lines of therapy since initial diagnosis of metastatic disease and time from initial diagnosis to NGS test.
Results
Overall, 10,174 pts had RET-WT and 27 pts had RET-fp tumours. Median OS was numerically lower in pts with RET-fp (6.6 months [95% CI 2.2–10.5]) vs those with matched RET-WT tumours (n=108; 11.4 months [95% CI 7.9–16.8]; Model 1, HR: 1.61 [95% CI 0.98–2.65]; Model 2, HR: 1.52 [95% CI 0.93–2.48]). Pt characteristics are shown in the Table; known oncogenic co-alterations were uncommon in RET-fp pts. Table: 110P
| RET-WT (n=10,174) | Matched RET-WT (n=108) | RET-fp (n=27) | |
| Age, mean (SD) | 62.6 (11.9) | 65.8 (8.8) | 64.7 (10.1) |
| ECOG PS, % | |||
| 0–1 | 56.4 | 58.3 | 55.6 |
| ≥2 | 12.2 | 3.7 | 3.7 |
| Missing | 31.4 | 38.0 | 40.7 |
| Practice type, % | |||
| Community | 11.5 | 11.1 | 11.1 |
| Academic | 88.5 | 88.9 | 88.9 |
| Previous lines of therapy, % | |||
| 0–2 | 60.1 | 51.9 | 51.9 |
| ≥3 | 16.6 | 3.7 | 3.7 |
| Missing | 23.3 | 44.4 | 44.4 |
| Tumour type (RET-fp N≥3), % | |||
| Colorectal | 35.9 | 29.6 | 29.6 |
| Pancreatic | 16.6 | 14.8 | 14.8 |
| Thyroid | 1.0 | 14.8 | 14.8 |
| Breast | 14.8 | 11.1 | 11.1 |
| Neuroendocrine | 3.9 | 11.1 | 11.1 |
| Co-occurring biomarkers, % | |||
| NTRK | 0.2 | 0 | 0 |
| ROS1 | 0.2 | 0 | 0 |
| ALK | 0.2 | 0 | 0 |
| BRAF | 5.0 | 5.6 | 0 |
| EGFR | 0.9 | 1.9 | 0 |
| KRAS | 33.7 | 28.7 | 0 |
| MET | 0.1 | 0 | 0 |
| ERBB2 | 3.3 | 2.8 | 7.4 |
| Tumour mutational burden, % | |||
| Low | 54.5 | 54.6 | 33.3 |
| Intermediate | 17.2 | 20.4 | 25.9 |
| High | 2.0 | 1.9 | 7.4 |
| Missing | 26.2 | 23.1 | 33.3 |
Conclusions
This study selected a small cohort of RETi-naïve pts in the CGDB. Despite the small sample, pts with RET-fp tumours had numerically higher risk of death vs pts with RET-WT tumours. This highlights the unmet need for effective RETi therapies that could improve the survival of pts with RET-fp metastatic solid tumours.
Clinical trial identification
NCT03037385.
Editorial acknowledgement
Medical writing support for the development of this abstract, under direction of the authors, was provided by Claire White, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
P. Garrido Lopez: Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, MSD, Medscape, Novartis, Pfizer, Roche, Takeda, Touchtime; Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Sanofi. S. Siena: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Bayer, BMS, CheckmAb, Daiichi Sankyo, Guardant Health, Menarini, Merck, Novartis, Roche-Genentech, Seagen. M. Taylor: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eisai Inc., Novartis, Merck, Pfizer, Bayer, Sanofi/Genzyme, Regeneron, Bayer, Loxo Oncology, Blueprint Medicines, Immuneonc, Exelixis, Cascade Prodrug; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Eisai Inc., Merck, Blueprint Medicines. A. Beringer: Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche AG; Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche AG. W. Bordogna: Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. O. Fajardo, C. Nikolaidis: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.