1. Results: Patient details Results: QoL
A Phase 2 study of anastrozole in recurrent estrogen(ER)/progesterone (PR) positive endometrial cancer: The PARAGON trial – ANZGOG 0903
L Mileshkin1*, R Edmondson2,R O’Connell3, K Sjoquist3, D Cannan3, R Jyothirmayi4, P Beale5 ,A Bonaventura6, J Goh7 ,
M Hall8 , A Clamp9, J Green10, R Lord10, J Scurry6, M Friedlander11 on behalf of the PARAGON study group
1 Peter MacCallum Cancer Centre, Melbourne, Australia; 2 St Mary’s Hospital, Manchester, UK; 3 NHMRC Clinical Trials Centre, Sydney, Australia; 4 Maidstone Hospital, Kent, UK; 5 Chris O’Brien Lifehouse, Sydney, Australia; 6 Calvary Mater Newcastle, Newcastle, Australia; 7 Royal Brisbane and Women’s Hospital, Brisbane, Australia; 8 Mount Vernon Cancer Centre, Middlesex, UK; 9 The Christie NHS Foundation Trust, Manchester, UK; 10 The Clatterbridge Cancer Centre, Liverpool and Wirral, UK; 11 Royal Hospital for Women/Prince of Wales Hospital, Sydney, Australia
NHMRC
Clinical Trials Centre
Background
Results: Patient details
Results: QoL
Many endometrial cancers express estrogen and/or progesterone receptors (ER/PR). There are variable reported response rates to hormonal therapies and conflicting predictors of response.
Aromatase inhibitors are more active than tamoxifen in ER/PR positive breast cancer. Prior reports of use in endometrial cancer suggest low response rates without selection for HR+ disease, with impact of treatment on QOL unclear.
The aim of PARAGON is to investigate anastrozole in patients with various ER/PR positive metastatic gynaecological cancers in a series of 7 individual phase 2 studies embedded in a basket protocol, with recruitment to the endometrial sub-group complete. (Australian New Zealand Clinical Trials Registry: #ACTRN )
Characteristic
Category
Percentage %
ECOG 1 2
47.6
41.7
10.7
Lines of Prior Chemotherapy
2-3 50
34.5
15.4
Tumour Grade
1-2 3
n/a
64.3
28.6
7.1
Age
Median age = 69 (37-89)
Treatment free interval
< 6 months
33.3
Prior radiation
Yes
66.7
QoL data was not available for 5 of the 84 registered patients. Of the remaining 79, 71 had both baseline and follow-up QoL data
Patients who had a clinical benefit at 3 months (SD/PR) were significantly more likely to have clinically significant improvements in several domains of QOL than progressors: emotional functioning (39 vs 6%:p = 0.002)
cognitive functioning (45 vs 19%:p = 0.021)
fatigue (47 vs 19%:p = 0.015)
global health status (42 vs 9%:p = 0.003)
Clinical benefit also associated with significantly improved mean change scores after 2-3 months for: social functioning, financial problems, pain, appetite loss and constipation
Methods and Objectives
Single-arm, open label trial of anastrozole, 1 mg/d in post-menopausal patients with ER and /or PR positive hormone naive recurrent endometrial cancer. Treatment continued until progressive disease (PD) or unacceptable toxicity.
Primary Objective: To determine
Clinical benefit rate at 3 months – proportion achieving response (partial or complete) or stable disease by RECIST v1.1
Secondary Objectives: To determine
Progression-free survival; Response duration; Quality of life (QoL); and
Proportion of patients experiencing grade 3 or 4 toxicities
QoL was assessed using the EORTC QLQ-C30/FACT-ES at baseline, monthly for the first 3 months and then 3 monthly until PD. The proportion of patients whose score improved by 10-points (considered clinically relevant) was calculated for each QLQ-C30 subscale. Linear regression was used to compare the change in scores between patients who achieved a 3-month clinical benefit and those with PD.
Results: Disease outcomes
Clinical benefit rates at 3 months = 44% (95% CI 34 – 55%)
Best RECIST response : Partial response = 7%
Stable disease = 36.6%
Progression = 56.1%
Median Progression-Free Survival = 3.2 months (95% CI 2.8 – 5.4)
Median duration of clinical benefit = 5.6 months (95% CI 3 – 13.7)
6 patients still on treatment for an average of 20 months (range 13.8 – 25.1)
Toxicity as expected: No treatment-related grade 3-4 toxicities
Difference in change in mean pain scores
Clinical benefit at 3 months
(n=35)
Progressors
P Value
2 months
-3.9
+4.7
P = 0.069
3 months
-4.5
+13
P = 0.008 20 40 60 80
100
Progression Free Survival (%) 82 71 36 22 19 16 13 12 10 5 4 3 2
Number at Risk: 6 8 14 18 24
Time (months) since registration
Progression-Free survival (n=72) 20 40 60 80
100
Progression-free survival % 39 36 25 16 13 11 9 4 3 2
>12 mths 5 1
6-12 mths 17
<6 mths
Number at Risk
Treatment-free interval: 6 8 10 12 14 18 22
Time (months) since registration
Treatment-free interval
Progression-Free Survival by Treatment-Free interval
Conclusions
Sample size: patients per subtype (minimum 75 for Endometrial Carcinoma) with defined stopping rules based on response and reviewed by independent data monitoring committee (IDMC).
84 eligible patients enrolled with 2 deemed not evaluable as received < 2 weeks of therapy
44% of patients with ER/PR positive endometrial cancer derived clinical benefit from anastrozole, associated with a significant improvement in QOL.
Anastrozole provided by Astra Zeneca and the study funded by grants from Cancer Australia
NHMRC
Clinical Trials Centre