H.-J. Lueck

AGO-OVAR 14: A retrospective study evaluating the reasons for non-participating in trials in patients with ovarian cancer (OC) treated in coordinating centers of the AGO Ovarian Cancer Study Group.

5081 Background: Retrospective analysis suggested that participation in clinical trials is associated with better outcome. However, it is not clear to what extent selection bias contributes to this observation. METHODS This study evaluated the reasons leading to the decision of not participating in clinical trials for OC in 2001. In a retrospective study the 16 AGO study coordination centers documented those pts who were not enrolled in current OC study protocols. Both cohorts, the OVAR-14 pts and pts recruited in prospective trials in the same period were compared. RESULTS Overall, 273 pts with OC FIGO-stage IIB-IV were enrolled of whom 138 (51%) and 135 (49%) pts were included in OVAR-14 and in prospective clinical trials, respectively. 93/138 pts. (67%) did not meet the inclusion criteria for clinical trials. The most common reasons were a history of 2nd malignancy (24 pts, 17%) and impaired renal function (GFR < 60 ml/min, 39 pts, 28%, of whom 51% had a GFR > 50 ml/min). Further 28 pts (20%) refused participation in a prospective study. 17 pts. (12%) were not recruited although they met the inclusion criteria (investigators decision). The OVAR-14 pts were older than pts treated in prospective studies (median age 65.8 vs 57.2 yrs.). There were no significant differences with respect to FIGO stage. OVAR-14 pts underwent less radical surgery and more frequent had residual disease of 2 cm or above: 48 pts (34,8%) vs 35 pts (25,9 %) in clinical studies. However, 85/138 pts (62%) were treated with carboplatin-paclitaxel, the standard arm in all AGO studies. CONCLUSIONS Future analysis should reveal if any change in inclusion criteria might increase study participation without compromising safety. Therefore, required GFR was reduced to 50 ml/min in the ongoing AGO trial (OVAR-9). Long-term follow-up should determine whether a history with prior malignancies without relapse should maintain an exclusion criteria in trials for advanced OC. Improving education for both pts and investigators might improve recruitment in clinical trials as well. No significant financial relationships to disclose.

PD06-07: COMPliance and Arthralgias in Clinical Therapy (COMPACT): Assessment of the Incidence and Severity of Arthralgia, Treatment Costs and Compliance within the First Year of Adjuvant Anastrozole Therapy.

Introduction: Aromatase inhibitors (AI) are well established as adjuvant endocrine treatment for postmenopausal (PMP) women with HR+ early breast cancer (EBC). However, according to retrospective data, compliance to adjuvant endocrine therapy for EBC may drop to below 70% after one year and to as low as 50% by year 4. In clinical trials, AI are significantly more frequently associated with arthralgia than tamoxifen. Yet, prospective real world data on the effects of AI-associated arthralgia on patient compliance, patient outcomes as well as treatment costs of arthralgia are lacking. Methods: COMPACT is an open, prospective, non-interventional study assessing the incidence and severity of arthralgia, treatment costs, and compliance within the first year of adjuvant anastrozole therapy in PMP women with HR+ EBC. The study is sponsored by AstraZeneca Germany and supported by three major German health insurance funds [GWQ ServicePlus AG, DAK, TK]. Patients on adjuvant treatment for 3–6 months were enrolled at 620 breast centres and practices throughout Germany and stratified by, a) initial adjuvant anastrozole therapy or, b) switch from tamoxifen to anastrozole. All patients receive regular standardized information about EBC from baseline to week 20 to support treatment compliance. Data on patient demographics, occurrence of and treatment of arthralgia, and quality of life will be collected at baseline, 3, 6 and 9 months. Primary endpoints are scaled data on arthralgia, assessed with a visual analogous scale (VAS) via patient questionnaire, and compliance to anastrozole in both strata, assessed by patient and investigator questionnaire. Secondary endpoints include the incidence of arthralgia, treatment costs, reasons for non-compliance, and the influence of arthralgia on clinical outcome. For a subgroup of patients data on arthralgia treatment and compliance will be validated with corresponding data of the participating health insurance funds. Results: Between April 2009 and February 2011, 2313 patients were recruited, 2007 receiving upfront anastrozole and 306 patients on switch therapy. Preliminary baseline data for 2313 patients show the following patient characteristics: mean age 64.5 years, mean BMI 27.7. Only 16.8% of patients had received hormone replacement therapy prior to their cancer. 41.5% of patients had concomitant symptoms relating to skeleton or musculature, and 11.9% stated arthralgias existing prior to anastrozole treatment. 13.1% reported a worsening of pre-existing arthralgias or new arthralgia after starting on anastrozole treatment. Conclusion: COMPACT aims to provide valid real world data on the incidence and severity of AI-associated arthralgia, treatment modalities and treatment costs. Our results will help to understand and better counsel patients about AI-associated arthralgia to improve adherence to AI-treatment, breast cancer outcomes, and therapy costs. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD06-07.

P5-17-05: 24 Months Follow-Up Results from PACT (Patient's Anastrozole Compliance to Therapy Programme), a Non-Interventional Study Evaluating the Influence of a Standardized Information Service on Compliance in Postmenopausal Women with Early Breast Cancer.

Introduction: According to recent retrospective studies, compliance to adjuvant endocrine therapy for early breast cancer (EBC) may drop to below 70% after one year and to as low as 50% by year 4. PACT aimed to increase treatment adherence in postmenopausal women taking an adjuvant aromatase inhibitor via a standardized information service (educational arm). Yet, after 12 months, there was no difference in compliance between the standard and educational arm (reported at this meeting 2010). Methods: PACT is a prospective, randomised, two-arm parallel-group study in Germany, sponsored by AstraZeneca (NCT00555867). Postmenopausal women on anastrozole for hormone-receptor positive (HR+) EBC were randomized to routine clinical care alone or to receive additional standardized information (educational arm) at nine times over the first 12 months of adjuvant therapy. Primary endpoints were compliance and persistence rates in the educational versus routine arm after 12 months. Secondary endpoints included longer follow-up, reasons for non-compliance, influence of baseline characteristics, and clinical outcome parameters (DSF, OS). Compliance was evaluated via patient questionnaires, prescription data and physician recall. Per protocol compliance was analysed only for patients with full documentation both by patients and physicians. Persistence was defined as the duration of time from initiation to discontinuation of therapy (Cramer et al 2007) and measured by prescription data. Results: PACT enrolled 4,923 female patients at 109 breast centres and 1,361 registered specialist practices from all regions in Germany. 4,397 patients were evaluable for baseline characteristics. 2,707 patients were evaluable for the primary endpoint (full documentation on tablet intake both by patients and physicians). No difference in compliance could be shown between the standard (88.2%) and the educational arm (88.3%) at 12 months (p=0.92, Fisher9s exact test). Persistence rates were 40.3% for the standard arm and 43.0% for the educational arm, respectively (p=0.17, Fisher9s exact test). At 24 months, data from 1539 patients was available for analysis compliance per protocol. Compliance rates were 88.7% (educational arm) and 87% (standard arm; p=0.29). Persistence again much lower at 41.1% and 42.1% (p=0.68). Variables influencing compliance were regular attendance to follow-up visits, participation in a cancer rehabilitation program, number of co-morbidities and current employment status. Persistence was influenced by factors such as tumour stage, joint pain and cancer rehab program participation. Conclusion: The addition of standardized information materials to standard clinical care did not lead to a significant increase in compliance or persistence rates at 12 or 24 months. With 4,923 women included, the PACT study represents the largest prospective study to evaluate the influence of educational material as well as baseline demographic and histopathological characteristics on the compliance and persistence to adjuvant endocrine therapy in postmenopausal patients with HR+ EBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-17-05.

Abstract P5-11-12: Quality of Life in the PACT-Programme (Patient's Anastrozole Compliance to Therapy Programme): Influence of a Standardized Information Service on Patient Satisfaction and Health Related Quality of Life in Postmenopausal Women with Early Breast Cancer (EBC)

Introduction: In recent years, patient reported outcomes have become increasingly a focus in clinical investigations. Health related quality of life (HRQoL) is now regularly evaluated in clinical trials, yet data on HRQoL in postmenopausal women receiving adjuvant aromatase inhibitor treatment for early breast cancer (EBC) is limited. Here, we present the 12 months results on HRQoL and patient satisfaction from PACT, a program which aims to increase awareness, motivation and adherence to adjuvant anastrozole therapy in routine clinical practice by adding regular standardized information (brochures and motivational letters) to standard clinical care. Methods: PACT is a prospective, randomised, two-arm parallel-group study with 60 months follow-up (NCT00555867, sponsored by AstraZeneca Germany). Postmenopausal women on anastrozole for hormone-receptor positive (HR+) EBC were randomized to routine clinical care alone or additional regular standardized information (educational arm) for the first year of adjuvant endocrine therapy. Primary endpoint was the compliance rate in the educational vs. routine arm after 12 months. Secondary endpoints include HRQoL and patient satisfaction, evaluated via EORTC IN-PATSAT32, QLQ-C30, and QLQ-BR23. The present analysis focuses on differences in HRQoL and patient satisfaction between the standard and educational arm and between compliant and non-compliant patients at 12 months after treatment initiation. Results: 4,923 patients were enrolled into PACT by Nov. 2008. Of these, 2,707 were evaluable for analysis of the primary endpoint compliance and the secondary endpoints patient satisfaction and HRQoL. Analysis of HRQoL and patient satisfaction scores showed no differences between the standard and the educational arm at 12 months. When comparing compliant vs. non-compliant patients, however, compliant patients reached significantly higher (=better) patient satisfaction scores in all domains. In addition, compliant patients achieved significantly higher (=better) scores in the HRQoL domains of physical functioning (p=0.04), emotional functioning (p=0.018), cognitive functioning (p=0.004), social functioning (p=0.005), and sexual enjoyment (p=0.047), as well as lower (=better) scores in the domains of fatigue (p=0.01), systemic therapy (p=0.003), and arm symptoms (p=0.03). After correction for multiple testing, statistically significant differences favouring compliant patients were retained in the areas of information provision and availability (p=0.0008 and p=0.0005, respectively). Conclusion: In postmenopausal patients with HR+ EBC assigned to adjuvant endocrine treatment with an aromatase inhibitor (anastrozole), HRQoL and patient satisfaction were not affected by the intervention. However, analysis of compliant vs. non-compliant patients revealed improved scores for patient satisfaction in multivariate analysis favouring compliant patients at 12 months after treatment initiation. PACT represents an important project in health outcomes research regarding adjuvant endocrine therapy in postmenopausal patients with HR+ EBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-12.