Abstract 1020
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 OncoCartaTM (Sequenom), TruSeq® Cancer Amplicon (Illumina), GeneReadTM 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.
Resources from the same session
5747 - The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified
Presenter: Fanny Preat
Session: Poster Display session 2
Resources:
Abstract
1837 - Oncological impact of re-excision for positive margin status after breast conserving surgery in invasive breast cancer
Presenter: Kenjiro Jimbo
Session: Poster Display session 2
Resources:
Abstract
4347 - Pneumonitis and fibrosis after breast cancer radiation.
Presenter: Jarle Karlsen
Session: Poster Display session 2
Resources:
Abstract
2280 - Prognosis of mastectomy with reconstruction after neoadjuvant chemotherapy: a nationwide study in Korean Breast Cancer Society
Presenter: Sungmin Park
Session: Poster Display session 2
Resources:
Abstract
804 - A negative prognosis of radiotherapy-induced lower lymphocyte to monocyte ratio in patients with breast cancer
Presenter: Chang-ik Yoon
Session: Poster Display session 2
Resources:
Abstract
2701 - Patient data to monitor clinical patterns in early and advanced breast cancer in Europe
Presenter: Francesco Giusti
Session: Poster Display session 2
Resources:
Abstract
1437 - A critical appraisal of quality indicators of breast cancer treatment in Belgium
Presenter: Didier Verhoeven
Session: Poster Display session 2
Resources:
Abstract
1534 - Predictors of adherence among post-menopausal women receiving adjuvant endocrine therapy for breast cancer in Ontario, Canada
Presenter: Phillip Blanchette
Session: Poster Display session 2
Resources:
Abstract
4363 - Evaluation of endocrine therapy and patients preferences in early breast cancer: results of Elena study
Presenter: Emilia Montagna
Session: Poster Display session 2
Resources:
Abstract
2679 - Baseline Quality of life (QoL) and chemotherapy related toxicities (CRT) in localized breast cancer (BC) patients (pts): the French multicentric prospective CANTO cohort study
Presenter: Idlir Licaj
Session: Poster Display session 2
Resources:
Abstract