Abstract 805P
Background
Gynecologic cancers in AYA are rare and research efforts to discover their distinct cancer biology are limited. Uncommon and aggressive subtypes of gynecologic cancer, such as mucinous and small cell ovarian carcinoma, are more frequent in AYA.
Methods
Two ongoing biomarker discovery studies are monitoring cancer evolution overtime, incorporating molecular profiling, clinical and pathological features in patients (pts) with high-grade serous ovarian cancer (HGSOC; NCT03419689) and other gynecologic cancers (NCT03420118) at Princess Margaret Cancer Centre. We retrospectively evaluated the clinical actionability of testing 555-562 genes (targeted NGS panel on DNA) using OncoKB annotation in ≤40 years (yrs) old pts enrolled between 2018-2020.
Results
From 566 enrolled pts, 69 pts with ≤40 yrs were identified (Table). Tumour NGS was performed in 65 pts. Median age at diagnosis was 34 yrs (13-40). Median lines of therapy was two (0-6) and 72% of pts had recurrent disease. At enrollment 96% of pts had ECOG ≤1. Ethnicity was white 62%, Asian 33%, others 5%. Median overall survival from diagnosis was 11.9 yrs (0.2-23.6). Actionable alterations (AA) were detected in 35% (23/65) of pts, most frequent being KRAS (20%), PTEN (9%), BRCA1 (6%) and NFL4 (5%). Level one (L1; FDA approved) AA were BRCA1, BRCA2, MMR genes, and level four AA (L4; biological evidence) were KRAS, PTEN and NFL4. Targeted therapy was administered to 15% (10/65) of patients through compassionate access (n=2; KRAS), clinical trial (n=4; KRAS, BRCA1, MMR genes) or standard of care (n=4; BRCA1/2). Best response was complete 30%, partial response 20%, stable disease 30% and not evaluable 20%. Median PFS was not reached in pts on L1 AA and was 1.3 yrs in those with L4 AA. Table: 805P
Disease site, pathology, and germline features (N=69)
| Origin | N (%) |
| OvaryCervixEndometriumOther | 38 (55)24 (35)4 (6)3 (4) |
| Histology Squamous cell cervixMucinous ovaryHGSOCLow grade serous ovaryMucinous cervixEndometrioid endometrialSmall cell carcinoma ovary hypercalcemic typeAdult granulosaGestational trophoblastic diseaseOther | 14 (20)12 (17)7 (10)6 (9)3 (4)3 (4)2 (3)2 (3)2 (3)18 (26) |
| Stage at diagnosis IVIIIIIIUnknown | 19 (28)9 (13)28 (41)7 (10)6 (9) |
| MMR IHC ProficientDeficientUnknown | 19 (28)2 (3)48 (70) |
| Germline alterations BRCA1 MMR genes SMARCA4 CHEK2 No pathogenic alterations identifiedNot performed | 4 (6)2 (2)1 (1)1 (1)13 (19)48 (70) |
Conclusions
35% of AYA with gynecologic cancers had actionable variants as per OncoKB using a DNA NGS panel. Genotype-matched therapy may help improve outcomes of AYA patients with relapsed gynecologic cancers.
Clinical trial identification
NCT03419689, NCT03420118.
Editorial acknowledgement
None
Legal entity responsible for the study
Princess Margaret Cancer Centre.
Funding
Princess Margaret Cancer Foundation, Ontario Institute for Cancer Research.
Disclosure
A. Madariaga Urrutia: Financial Interests, Personal, Invited Speaker: AstraZeneca. V. Bowering: Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Advisory Board, non-compensated: AstraZeneca; Non-Financial Interests, Personal, Advisory Board, non-compensated: GSK. A.M. Oza: Other, Institutional, Research Grant: AstraZeneca; Other, Personal and Institutional, Research Grant: GSK; Other, Personal and Institutional, Research Grant: Clovis; Non-Financial Interests, Personal, Advisory Board, Non-compensated: AstraZeneca; Non-Financial Interests, Personal, Advisory Board, Non-compensated: GSK; Non-Financial Interests, Personal, Advisory Board, Non-compensated: Clovis. S. Lheureux: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Eisai. All other authors have declared no conflicts of interest.