Abstract 105P
Background
Two ROS1 tyrosine kinase inhibitors have been approved for ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC). We performed a pan-tumor analysis of the incidence and characteristics of ROS1 fusions across all solid tumors.
Methods
A retrospective analysis was performed on ROS1-positive solid malignancies identified by targeted RNA sequencing and whole transcriptome sequencing of clinical tumor samples through Caris Life Science (Phoenix, AZ). Real-world overall survival (rwOS) was obtained from insurance claims data and calculated from either tissue collection to last contact or time on treatment (TOT) from start to finish of ICI. Comparison of survival was performed by Kaplan-Meier analysis.
Results
A total of 259 ROS1+ samples across 17 distinct solid malignancies were identified from approximately 175,350 tumors that underwent sequencing (88% from whole transcriptome; 12% from targeted RNA; (Table). ROS1+ NSCLC constituted 78.8% of the ROS1+ solid malignancies, followed by glioblastoma (6.9%) and breast cancer (2.7%). The frequency of ROS1 fusion was approximately 0.47% among NSCLC, 0.29% for glioblastoma and 0.04% for breast cancer. The mean tumor mutation burden for all ROS1+ tumors was 4.8 mutations/Mb (SD 2.8). The distribution of PD-L1 (22C3) expression among all ROS1+ malignancies were 0% (18.6%), 1%-49% (29.4%), and > 50% (52.0%). The mean junctional read among all tumor types was 54.7 with NSCLC at 64.0 (SD 107.77), glioblastoma at 32.2 (SD 55.12) and breast cancer at 6.7 (SD 5.20). The most common genetic co-alterations of ROS1+ NSCLC were TP53 (29.1%) and SETD2 (7.3%). Although the analysis was limited in sample size, ROS1+ in glioblastoma may represent a potential poor prognostic factor (HR 0.56 95% CI: 0.23-1.35, p=0.19). Also, treatment with immunotherapy in ROS1+ fusions demonstrated shorter survival than those treated with ROS1 TKIs (HR 2.77 95% CI: 0.85-9.03, p=0.08). Table: 105P
| All | NSCLC | Glioblastoma | Breast | |
| N | 259 | 204 | 18 | 7 |
| Age median(range) | 63 (18-89) | 65 (27-89) | 63 (41-89) | 60 (40-77) |
| Male | 113 | 86 | 11 | 0 |
| Female | 146 | 118 | 7 | 7 |
| Sequencing methods | ||||
| Targeted RNA (Archer) | 55 | 49 | 4 | 1 |
| WTS | 204 | 155 | 14 | 6 |
| Mean junction read | 54.7 | 64.0 | 32.2 | 6.7 |
| TMB (median) | 4 | 4 | 3 | 5 |
Conclusions
ROS1 fusions occurred at a low frequency among a diverse range of solid tumors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Nagasaka: Financial Interests, Personal, Advisory Board: AstraZeneca, Caris Life Sciences, Daiichi Sankyo, Novartis, EMD Serono, Janssen, Pfizer, Genentech, Mirati, Regeneron, Silverback; Financial Interests, Personal, Invited Speaker: Takeda, Blueprint; Financial Interests, Personal, Expert Testimony: Lilly; Financial Interests, Personal, Other, Travel: AnHeart. Y. Baca: Financial Interests, Personal, Stocks/Shares: Caris Life Sciences. J. Xiu: Financial Interests, Personal, Stocks/Shares: Caris Life Sciences. J.J. nieva: Financial Interests, Personal and Institutional, Research Grant: Merck, Genentech; Financial Interests, Personal, Advisory Board: Mindmed, AstraZeneca, Naveris, G1 Therapeutics, Aadi Biosciences; Financial Interests, Personal, Ownership Interest: Epic Sciences, Quantgene, Indee Bio. A. VanderWalde: Financial Interests, Personal and Institutional, Research Grant: Merck, Genentech; Financial Interests, Personal, Advisory Board: Mindmed, AstraZeneca, Naveris, G1 Therapeutics, Aadi Biosciences; Financial Interests, Personal, Ownership Interest: Epic Sciences, Quantgene, Indee Bio. J.J. Swensen: Financial Interests, Personal, Stocks/Shares: Caris Life Sciences. D. Spetzler: Financial Interests, Personal, Stocks/Shares: Caris Life Sciences. W.M. Korn: Financial Interests, Personal, Stocks/Shares: Caris Life Sciences. S.V. Liu: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Blueprint, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/ Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Lilly, Merck/MSD, Novartis, Regeneron, Sanofi, Takeda, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Alkermes, Bayer, Blueprint, Bristol Myers Squibb, Elevation Oncology, Genentech, Gilead, Merck, Merus, Nuvalent, Pfizer, Rain Therapeutics, RAPT, Turning Point Therapeutics. S.I. Ou: Financial Interests, Personal, Invited Speaker: Pfizer, Roche; Financial Interests, Personal, Advisory Board: JNJ/Janssen, Elevation Oncology; Financial Interests, Personal, Stocks/Shares: Turning Point Therapeutics, Elevation Oncology; Financial Interests, Institutional, Invited Speaker: Pfizer, Mirati, JNJ/jassen, Merus. All other authors have declared no conflicts of interest.