Proffered papers session


Programme session type(s): Proffered papers session

Chair: Matt Seymour, NCRI and NIHR, UK
Presenter: Joanne Haviland, The Institute of Cancer Research, UK
Presenter: Nalinie Joharatnam, MRC Clinical Trials Unit at UCL, UK
Presenter: Rosalind Glasspool, Beatson West of Scotland Cancer Centre, UK
Presenter: Stephan Dreyer, University of Glasgow, UK

08:15-09:00

Room: Boisdale

Proffered paper sessions are dedicated to the highest scoring abstracts chosen by the scientific committee. They are grouped by type of science presented (following the main Conference streams) and in broad terms cover basic, translational and clinical research.

The abstracts being presented in this session are:
1. Aspirin use after radical cancer therapy – feasibility and toxicity data from the Add-Aspirin trial – Nalinie Joharatnam

2. FAST-Forward phase 3 RCT of 1-week hypofractionated breast radiotherapy: 3-year normal tissue effects – Joanne Haviland

3. Defining DDR deficiency and Replication Stress in Pancreatic Cancer – Stephan Dreyer

4. Progression free survival as a surrogate endpoint for overall survival in first-line therapy of advanced ovarian cancer: A Gynecologic Cancer InterGroup (GCIG) individual patient-level meta-analysis – Rosalind Glasspool

Aspirin use after radical cancer therapy – feasibility and toxicity data from the Add-Aspirin trial
Speaker: Nalinie Joharatnam
Affiliation: MRC Clinical Trials Unit at UCL

Abstract:

Pre-clinical, observational and randomised evidence suggests aspirin may prevent or delay the development of cancer and metastases, and is strongest for colorectal and gastro-oesophageal cancer. However, concerns around feasibility, adherence and tolerability (particularly serious bleeding) have limited aspirin use for cancer chemoprevention.

Method

Add-Aspirin is a double-blind, randomised-controlled trial encompassing 4 individually powered phase III trials in early-stage breast, prostate, colorectal and gastro-oesophageal cancer, evaluating the effect of aspirin after radical therapy. All participants initially take open-label aspirin (100mg daily) for 8 weeks (run-in), to assess adherence and toxicity prior to randomisation (1:1:1, aspirin 300mg, aspirin 100mg or matched placebo for ≥5 years). A pre-planned feasibility analysis was performed to assess tolerability and adherence when >2000 participants had completed the run-in period.

Results

Between October 2015 and October 2017, 3494 of a targeted 11000 participants were registered from 165 sites in the UK; recruitment rates differed across tumour sites compared to predictions. Run-in data (n=2253) showed good adherence: 95% took 6-7 tablets/week and 85% proceeded to randomisation, with rates consistent across tumour cohorts. Main reasons for not proceeding to randomisation were toxicity (mostly minor, grade 1/2) and/or patient choice, with only 0.7% (16/2253) of participants experiencing toxicity requiring discontinuation during the run-in. Fewer than 1% (13/2253) experienced a grade > 3 toxicity (including one lower gastrointestinal bleed in a prostate cancer participant; no upper gastrointestinal bleeds).

Conclusion

The data demonstrate that aspirin is well-tolerated over an 8-week run-in, and acceptable to patients after radical cancer therapy, with low toxicity rates in all tumour cohorts, including gastro-oesophageal participants. A run-in approach may be useful in adjuvant (or prevention) studies for reducing the risk of non-adherence and participant attrition at a later date. Trial recruitment continues with >5000 participants now registered from the UK and India.

Progression free survival as a surrogate endpoint for overall survival in first-line therapy of advanced ovarian cancer: A Gynecologic Cancer InterGroup (GCIG) individual patient-level meta-analysis
Speaker: Rosalind Glasspool
Affiliation: Beatson West of Scotland Cancer Centre

Abstract:

Introduction: Overall survival (OS) is considered the gold standard endpoint for controlled clinical trials but it requires extended follow-up (median OS> 40 months for first line therapy) and large sample sizes. The UK contributed 3 trials to this Gynaecological Cancer Intergroup (GCIG) meta-analysis. The objective was to evaluate whether progression free survival (PFS) based on CA125 measurements confirmed by radiological exam or combined GCIG criteria is a surrogate endpoint for OS in advanced ovarian cancer (AOC).

Method

Methods: Using the meta-analytic approach on trials published after 2000, correlations between PFS and OS at the individual level, and between treatment effects on PFS and on OS at the trial level, were estimated using Kendall’ tau and copula bivariate (R2Copula) models respectively. Criteria for PFS surrogacy required R2Copula ≥ 0.80.

Results

Results: We analyzed individual patient data (IPD) from 10,502 patients in 16 randomized first line trials of standard (n=7), intensification (n=5) and maintenance (n=4) . No heterogeneity in the treatment effects across trials was detected. High correlations were found at the individual level (tau = 0.77) but low correlation at the trial level (R2Copula = 0.2). Sub-group analyses led to similar results.

Endpoint / Trial type

Trials
N (pts)

taua

R2Copulaa

R2

Overall

16 (10502)

0.77

0

0.2

CA125 confirmed by radiological exam

10 (5319)

0.75

0.01

0.24

GCIG criteria

5 (4076)

0.78

0.14

0.04

Carbo-Tax as control

10(7336)

0.72

0

0.2

Standard or intensification

12 (7704)

0.77

0.20

0.24

Maintenance

4 (2798)

0.64

0.14

0.01

a tau and R2 values range from 0 (no association) to 1 (perfect correlation)

Conclusion

Conclusions:This large IPD meta-analysis did not establish PFS as a surrogate endpoint for OS in first line treatment of AOC. The analysis was limited by the narrow range of treatment effects observed and/or post study treatment. 

FAST-Forward phase 3 RCT of 1-week hypofractionated breast radiotherapy: 3-year normal tissue effects
Speaker: Joanne Haviland
Affiliation: The Institute of Cancer Research

Abstract:

FAST-Forward aims to identify a 1-week 5-fraction schedule of adjuvant radiotherapy as effective and safe as the UK standard 15-fraction regimen for early breast cancer. We report normal tissue effects (NTEs) up to 3 years (shown in previous breast radiotherapy trials to predict comparisons at 5+ years).

Method

The FAST-Forward trial (ISRCTN19906132; NIHR-HTA 09/01/47) randomised patients (pT1-3 pN0-1 M0) following breast conservation surgery or mastectomy (immediate reconstruction permitted) to 40Gy/15 fractions/3 weeks (control), 27Gy or 26Gy/5 fractions/1 week to whole breast or chest wall. A tumour bed boost of 16Gy/8 fractions or 10Gy/5 fractions was given where indicated. NTEs were assessed annually by clinicians, by patients at baseline, 3, 6, 12 and 24 months and from photographs at 2 years compared with a pre-radiotherapy baseline. Schedules were compared using cross-sectional and survival analyses. A lymphatic sub-study is ongoing.

Results

From 09/2011-06/2014, 4096 patients were recruited (40Gy: 1361, 27Gy: 1367, 26Gy: 1368). Median follow-up is 48 months (IQR 37-50). Marked NTEs at 2 or 3 years were uncommon (<5% for clinician and photographic assessments, <15% for patient assessments). Clinician assessments of individual NTEs at 3 years and patient assessments at 2 years were similar between schedules. 2-year prevalence of mild/marked change in photographic breast appearance was statistically significantly higher for 27Gy (16.1%, 95%CI 12.9-19.9%) compared with 40Gy (8.3%, 6.0-11.5%), but similar for 26Gy (10.6%, 8.0-13.9%) and 40Gy. 3-year cumulative incidence rates of any clinician-assessed moderate/marked NTE in the breast/chest wall were highest for 27Gy (28.8%, 26.4-31.4%) but similar for 26Gy (21.8%, 19.6-24.2%) and 40Gy (20.8%, 18.6-23.2%).

Conclusion

Levels of marked NTEs were low for all schedules. Late effects after 26Gy in 5 fractions over 1 week were similar to 40Gy in 15 fractions over 3 weeks.