1020 - Clinical impact of molecular profiling of cervical cancer (CC) patients (pts) in a dedicated Phase I (P1) unit

Background

Metastatic CC prognosis remains poor. Molecular characterisation (MC) allows better understanding of the mutations (mut) driving carcinogenesis or treatment resistance. We report the cervical tumour MC of pts in a P1 unit and its clinical implications.

Methods

CC pts referred to the P1 unit of The Royal Marsden Hospital from 2011-18 underwent tumour molecular profiling using OncoCarta^TM (Sequenom), TruSeq^® Cancer Amplicon (Illumina), GeneRead^TM custom DNA damage (Qiagen) or FoundationOne^® panel. Retrospective data was extracted from electronic medical records.

Results

Of the 37 pts (median age: 34.7 years) analysed, 45.9% had squamous histology, and 37.8% were FIGO stage 2 at diagnosis; 34 different pathogenic mut were identified with 70.3% of pts having mut. PIK3CA mut were the most common (32.4%), followed by KRAS (13.5%), APC (8.1%), TP53 (8.1%), PTEN (5.4%), KDR (5.4%), ATM (5.4%), STK11 (5.4%) and BRCA1 (5.4%). 40.5% (15/37) patients had a potentially actionable mutation. Median overall survival (mOS) was 36 months (mo) in study population, 33 mo in KRAS mut, 40 mo in PIK3CA mut, 52 mo in APC mut and 40 mo in the mut-negative group; however, this difference was not statistically significant. In the KRAS mut group, 60% were adenocarcinoma and 40% adenosquamous. All KRAS mut pts had FIGO stage 2/3 at diagnosis. 80% had visceral metastasis when referred to the P1 unit; whereas in the PIK3CA mut group, tumour histologies were 33.3% squamous, 25% adenocarcinoma, 25% adenosquamous, 8.3% mucinous, 8.3% uncommon histologies. In the PIK3CA mut group, 75% were stage 1/2 at diagnosis, and 41.6% had visceral metastasis when referred. 5.4% (2/37) of pts were allocated to a P1 trial based on the finding of a PIK3CA mut with a mOS of 40 mo compared to 36 mo for the total population (p = 0.6). One pt received an AKT inhibitor (i) but developed progressive disease (PD) after 3 cycles; the other received a PI3K i with PD after 4 cycles.

Conclusions

Our study corroborates existing knowledge of the association between KRAS mut and adenocarcinoma histology in CC which confers worse prognosis. The high rate of potentially actionable mut indicates the increasing scope for targeted treatment trials in CC, thus prompting early MC which may improve pt allocation to P1 trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The Institute of Cancer Research and The Royal Marsden Foundation Trust.

Funding

The Institute of Cancer Research and The Royal Marsden Foundation Trust.

Disclosure

S. Banerjee: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Honoraria/reimbursement: Tesaro; Honoraria (self), Honoraria/reimbursement: Clovis; Honoraria (self), Honoraria/reimbursement: Merck Serono; Honoraria (self), Honoraria/reimbursement: Nucana; Honoraria (self), Honoraria/reimbursement: Immunogen; Honoraria (self), Honoraria/reimbursement: Seattle Genetics; Honoraria (self), Honoraria/reimbursement: Roche; Honoraria (self), Honoraria/reimbursement: Gamamabs. J.S. de Bono: Honoraria (self), Non-remunerated activity/ies: Astellas Pharma; Honoraria (self), Research grant / Funding (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (self): Genentech/Roche; Honoraria (self): Pfizer; Honoraria (self), Non-remunerated activity/ies: Sanofi; Honoraria (self): Bayer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Merck Serono; Honoraria (self): Merck Sharp & Dohme; Non-remunerated activity/ies: Genmab; Non-remunerated activity/ies: GlaxoSmithKline; Non-remunerated activity/ies: Orion Pharma GmbH; Non-remunerated activity/ies: Qiagen; Non-remunerated activity/ies: Taiho Pharmaceutical; Non-remunerated activity/ies: Vertex; Licensing / Royalties, Royalties paid to Institution, no personal income: Abiraterone Rewards to Inventors; Licensing / Royalties, Royalties paid to Institution, no personal income: PARP inhibitors and DNA repair defects. U. Banerji: Honoraria (self), Precision Medicine - Advanced Prostate Cancer Meeting, London UK -30/11/2018: Astellas; Honoraria (self), Advisory / Consultancy, Translational Clinical Oncology Advisory Board, London, 24/07/2018; FIH Precision Oncology SAB, Frankfurt, 10-11/11/2015: Novartis; Advisory / Consultancy, Clinical Advisory Board, London, 19/03/2018 and 12/02/2015: Karus Therapeutics; Advisory / Consultancy, GI Advisory Board, London, 2/12/2017: Phoenix ACT; Honoraria (self), European Digestive Oncology Research Forum, London, 27-28/11/2017: Eli Lilly; Honoraria (self), KOL ERK Workshop, New Orleans, 17/04/2016; HSP90 Workshop, Washington DC,8/03/2014: Astex; Honoraria (self), AUY922 meeting, New Jersey, USA,12/02/2015: Vernalis; Research grant / Funding (institution), ONX-0801:Funding for investigator-initiated Phase I trial: Onyx Pharmaceuticals; Research grant / Funding (institution), ONX-0801:top-up funding for investigator-initiated phase I trial: BTG International; Research grant / Funding (institution), RAF/MEK: funding for investigator-initiated phase I trial: Chugai; Research grant / Funding (institution), TAX-TORC: funding for investigator-initiated phase I trial: AstraZeneca; Research grant / Funding (institution), FRAME: funding for investigator-initiated phase I trial: Verastem. A. Minchom: Travel / Accommodation / Expenses: Loxo; Advisory / Consultancy: Janssen; Honoraria (self): Faron; Speaker Bureau / Expert testimony: Bayer Media Event. J. Lopez: Advisory / Consultancy: Genmab; Advisory / Consultancy: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Research grant / Funding (institution), Travel / Accommodation / Expenses: Basilea. All other authors have declared no conflicts of interest.