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Found 2 Presentations For Request "34p"
34P - Molecular markers of response to different chemotherapeutic agents in RAS / BRAF mutated colon cancer cell lines
- Kevin Doello (Granada, Spain)
Abstract
Background
RAS mutated colon cancer has a worse prognosis than wild type (wt) with a median of about 20 months of OS and the BRAF mutated with an OS of about 10 months. In addition, we frequently find patients with therapeutic exhaustion. The objective of the present study is the definition of molecular markers of response to traditional chemotherapeutic agents and new drugs studied in RAS / BRAF mutated colon cancer.
Methods
The following colon cancer cell lines were used: HCT15, T84, HT29 and SW480 (molecular characteristics are summarized in the table). These cell lines were assigned to 5-fluorouracil, oxaliplatin, irinotecan, gemcitabine, pemetrexed, trabectidine and eribulin at different doses for 72 hours in order to obtain the inhibitory concentration 50 values (IC50). Likewise, RT-PCR studies were carried out in order to determine the expression of P-glycoprotein.
Results
The results of IC50 (μM) obtained in the colon cancer cell lines for the different drugs are summarized in the table. The results of the RT-PCR revealed the presence of P-Glycoprotein in HCT15 and the absence of expression of this protein in the rest of the cell lines studied. The sensitivity to 5-FU and GMZ in the studies seems to correspond to the wt forms of p53 and SMAD4, this last closely related to p21. OXA sensitivity is related to the mutated forms of p53 and SMAD4. IRI is related to the degree of tumor cell differentiation, the most undifferentiated being more sensitive (CMS 1 and 4). IRI, PEM and TRABECT sensitivity is linked to the wt form of APC. In the case of ERIB, the most resistant line is the one that expresses P-glycoprotein.
T84 HCT15 SW480 HT29 2,76 6,23 6,57 8,6 6,06 2,47 2,44 1,77 18,24 9,61 4,24 22,15 0,21 0,3 0,4 0,61 0,24 0,21 0,06 0,31 0,00097 > 0,0075 0,00010 0,00090 0,00140 0,00170 0,00045 0,00200 RAS mut RAS mut RAS mut BRAF mut wt mut mut mut MSS MSI MSS MSS mut mut mut mut mut mut wt mut wt wt wt mut 2 (differentiated) 1 (undifferentiated) 4 (undifferentiated) 3 (differentiated)
Conclusions
1. The sensitivity to fluoropyrimidines is not related to the instability of microsatellites in the cell lines studied. 2. Sensitivity to different drugs correlates with different molecular markers in each case. 3. These results could help to choose the most appropriate treatments in advanced colon cancer and even when the basic therapeutic lines have been exhausted.
Legal entity responsible for the study
SAS.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
824P - Real-world-data (RWD) on platinum (Pt) outcomes after PARP inhibitors (PARPi) progression in high grade serous ovarian cancer (HGSOC) patients (p)
- Andrea Plaja Salarich (Badalona, Spain)
Abstract
Background
PARPi maintenance after Pt-based chemotherapy (CT) significantly improves progression-free survival (PFS) and PFS to subsequent (ssq) chemotherapy (PFS2) in relapsed HGSOC. However, crossed mechanisms of action and resistance between PARPi and Pt cast doubts on the benefit from ssq Pt after PARPi progression. We provide RWD on this issue.
Methods
We included HGSOC p treated with ssq CT after progression to maintenance PARPi until 31st Dec 2019 in 3 large hospitals. Endpoints were overall response rate (ORR), median (m) PFS and overall survival (mOS) to ssq Pt after PARPi. Analysis were also performed according to 3 populations: p who received ssq non-Pt CT, p with Pt-free interval (PFI) 6-12 months (mo) and p with PFI >12 mo.
Results
54 p were identified (57.4 % BRCAmut). 4p (7.4%) received PARPi after 1st line CT, 25 (46.3%) after 2nd line, and 25 (46.3%) after ≥3rd line. 34p (63%) received olaparib and 20 (37%) niraparib. mPFS of PARPi as maintenance in the recurrent setting was 7.5 mo and PFS2 15.4 mo. Distribution of ssq CT schemes and their best responses are shown in the table. ORR to ssq Pt was 33.3%, and progression disease (PD) 28.6%. ORR in p who received ssq Pt-free CT, p with PFI 6-12 mo, and p with PFI >12 mo were 28.6%, 22.7% and 45%, respectively. The 4 identified complete responses (CR) occurred among BRCAmut p receiving PARPi in the recurrent setting and PFI>12. Survival endpoints of ssq CT are shown in the table. mPFS and mOS were significantly longer in the PFI >12 subgroup versus the others. Survival did not change when excluding the 4p who received PARPi as 1st line (Table). *Evaluable p (n=49).
Non Pt-CT Pt-CT PFI 6-12 mo N=24 PFI >12 mo N=21 5 (55.6) 12 (50) 14 (66.7) 0.055 0.010 CR 0 0 4 (20) Partial response 2 (28.6) 5 (22.7) 5 (25) Stable disease 2 (28.6) 6 (27.3) 10 (50) PD 3 (42.9) 11 (50.0) 1 (5) 5.1(3.2-) 5.1 (4.0-9.0) 9.4 (6.7-14.0) 0.055 6.8 (3.12-) 14.2 (9.4-) 28.2 (11.9-) 0.018
Conclusions
Higher benefit from ssq Pt after PARPi was observed in the PFI>12 subgroup. Benefit from ssq Pt after PARPi in the PFI 6-12 subgroup was similar to benefit from CT in the non-Pt subgroup. The role of ssq Pt after PARPi in the PFI 6-12 subgroup warrants further research.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Plaja Salarich: Travel/Accommodation/Expenses: Angelini; Travel/Accommodation/Expenses: Roche. B. Pardo Burdalo: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: GSK. M. Gil-Martin: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: MSD. J.M. Piulats: Advisory/Consultancy: Clovis; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): BeiGene. C. Fina Planas: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Bristol-Myers. M.P. Barretina Ginesta: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: PharmaMar; Advisory/Consultancy, Speaker Bureau/Expert testimony: Clovis Oncology. M. Romeo Marin: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro; Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.