Abstract 1385
Background
Hyper-radiation sensitivity is enhanced in cells with mutant p53, which is ubiquitous in high grade serous ovarian cancer (HGSOC). Preclinical data suggests LDWART is a “chemosensitizer” and enhances paclitaxel cytotoxicity. We evaluated the safety and activity of LDWART concurrent with wP (LDWART+wP) in PROC.
Methods
Patients (pts) with PROC (progressive disease (PD) < 6 mth from last platinum therapy) were enrolled in a 3 + 3 dose de-escalation (part A) design, combining wP concurrent with fixed dose LDWART in 60 cGy fractions (twice daily on D1-2 of each week of wP), for 6 continuous weeks. Planned dose levels of wP were 80mg/m2, 70mg/m2, 60mg/m2. After 6 weeks of LDWART+wP, pts received wP chemotherapy alone until PD. Dose expansion (part B) with up to 10 HGSOC pts at maximum tolerated dose (MTD) of LDWART+wP, proceeded to confirm toxicity and activity.
Results
As of 30/4/2019, 10 pts were enrolled (3 part A, 7 part B). All part B pts had HGSOC. Median lines of prior therapy was 5 (range 1-8), including prior wP in 70%, and prior bevacizumab (bev) in 50% of pts. There was no dose-limiting toxicity (DLT) at wP 80mg/m2 (DLT period = 1st 3 weeks of LDWART+wP), which was deemed the MTD. 6/10 pts completed 6 weeks of LDWART+wP. Discontinuations were due to PD (3/10) or pt withdrawal (1/10). Common related all-grade adverse events (AEs) were nausea (60%), neutropenia (60%), fatigue (60%), neuropathy (40%), diarrhea (30%); common related grade ≥3 AEs were neutropenia (50%) and anemia (20%). Median progression free survival was 3.2 mth and overall survival was 13.5 mth. 9 pts were evaluable for response. 44.4% (4/9) of pts achieved biochemical response, defined as CA125 decrease >50% from baseline, 2/4 were confirmed. 1 pt had partial response (PR) despite PD on prior wP, and 5 pts had stable disease (SD), giving an overall response rate of 11.1% (1/9) and disease control rate (PR + SD > 6 weeks) of 66.7% (6/9). 3 pts had durable disease control, and completed 12, 18 and 21 weeks of wP respectively.
Conclusions
LDWART+wP (80mg/m2) for 6 weeks was safe and tolerable. Encouraging efficacy was seen in this heavily pre-treated population and LDWART+wP may be useful in the context of PROC where bev is contraindicated.
Clinical trial identification
NCT02545010.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
RIE2015 National Medical Research Council, National University Cancer Institute Singapore (NCIS) Centre Grant – NCIS Seed Funding.
Disclosure
D.S. Tan: Honoraria (self): Roche; Honoraria (self), Research grant / Funding (self): Bayer; Honoraria (self): MSD; Honoraria (self): Genmab; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Merck Serono; Honoraria (self): Tessa Therapeutics; Honoraria (self): Novartis; Research grant / Funding (self): Karyopharm. All other authors have declared no conflicts of interest.
Resources from the same session
5887 - Factors of importance in procuring tumoroids from colorectal liver metastasis biopsies for precision medicine.
Presenter: Lars Henrik Jensen
Session: Poster Display session 2
Resources:
Abstract
2196 - FUSAFE individual patient data meta-analysis (MA) to assess the performance of dihydropyrimidine dehydrogenase (DPD) gene polymorphisms for predicting grade 4-5 fluoropyrimidine (FP) toxicity
Presenter: Marie-Christine Etienne-Grimaldi
Session: Poster Display session 2
Resources:
Abstract
2859 - Treatments (tx) after progression to first-line FOLFOXIRI + bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts): A pooled analysis of TRIBE and TRIBE-2 studies by GONO.
Presenter: Daniele Rossini
Session: Poster Display session 2
Resources:
Abstract
3888 - Randomized phase III study of sequential treatment with capecitabine or 5-fluorouracil (FP) plus bevacizumab (BEV) followed by the addition with oxaliplatin (OX) versus initial combination with OX+FP+ BEV in the first-line chemotherapy for metastatic colorectal cancer: The C-cubed study
Presenter: Takeshi Nagasaka
Session: Poster Display session 2
Resources:
Abstract
1065 - Early tumour shrinkage (ETS), depth of response (DpR) and associated survival outcomes in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC) classified according to Köhne prognostic category: retrospective analysis of the panitumumab (Pmab) PRIME study
Presenter: Andrea Sartore-Bianchi
Session: Poster Display session 2
Resources:
Abstract
1702 - Randomized phase II trial of CAPOX with planned oxaliplatin stop-and-go strategy as adjuvant chemotherapy after curative resection of colon cancer (CCOG-1302 study)
Presenter: Hiroyuki Yokoyama
Session: Poster Display session 2
Resources:
Abstract
5104 - A metabolomic recurrence score for risk-stratification of elderly patients (pts) with early colorectal cancer (eCRC)
Presenter: Samantha Di Donato
Session: Poster Display session 2
Resources:
Abstract
5285 - RAS mutant allele fraction in plasma predicts benefit to anti-angiogenic based first line treatment in metastatic colorectal cancer
Presenter: Giulia Martini
Session: Poster Display session 2
Resources:
Abstract
1790 - Impact of prophylactic systemic antibiotics (SA) on outcome of patients (pts) with RAS-wildtype (RAS-wt) metastatic colorectal carcinoma (mCRC) treated with cetuximab-based first-line therapy. Subgroup analysis of the german non-interventional study ERBITAG
Presenter: Stephan Sahm
Session: Poster Display session 2
Resources:
Abstract
3059 - Intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): A randomized, multicenter, prospective, phase III trial
Presenter: Rongxin Zhang
Session: Poster Display session 2
Resources:
Abstract