Reduction In Chemotherapy Use Research Articles

Abstract PO5-02-04: Irish National Analysis of the Clinical and Economic impact of 21-gene Oncotype DX® testing in Early-Stage, 1-3 lymph node positive, Hormone Receptor positive (HR+), HER2-Negative (HER2-), Breast Cancer (BC)

Abstract PO5-02-04: Irish National Analysis of the Clinical and Economic impact of 21-gene Oncotype DX® testing in Early-Stage, 1-3 lymph node positive, Hormone Receptor positive (HR+), HER2-Negative (HER2-), Breast Cancer (BC)

Real-world impact of TAILORx on chemotherapy use and SOFT/TEXT on ovarian function suppression uptake in a population based-cohort of women 40 years and under with HR-positive, HER2-negative, axillary lymph node negative breast cancer.

534 Background: Gene expression profiling (GEP) testing is prognostic for distant recurrence risk in women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-), axillary lymph node negative (LN-) breast cancer (BC). The TAILORx trial generated prospective evidence demonstrating the 21-gene recurrence score (RS) is also predictive of chemotherapy (CT) benefit. The literature suggests that GEP testing reduces adjuvant CT prescription and is cost-effective. In the same era, the SOFT/TEXT trials demonstrated disease-free survival benefit for the addition of ovarian function suppression (OFS) to endocrine therapy in premenopausal women. Real-world uptake and impact of these advances in the management of HR+, HER2-, LN- BC in young women may be limited due to complex reasons. This retrospective study evaluated GEP and CT use post TAILORx and OFS use post SOFT/TEXT in women 40 years old or younger diagnosed with HR+, HER2-, LN BC from 2011 to 2020 in Alberta, Canada. Methods: Clinical variables were retrieved from the Alberta Health Services Cancer Care Breast Data Mart and through review of the electronic medical record. GEP testing and CT use were compared between 3 cohorts of women defined by diagnosis: pre RS funding/pre TAILORx (before April 2014), post RS funding/pre TAILORx (April 2014-May 2018), post TAILORx (June 2018 and beyond). OFS use was compared between 2 cohorts of women defined by diagnosis pre- and post SOFT/TEXT (May 2015). In subgroup analyses, we compared CT use by GEP status and RS category and OFS use by CT status. Results: Among the 291 women identified, GEP testing increased by 37% post GEP funding (pre 2% vs. post 39%; P = < .0001) and by additional 15% post TAILORx (pre 39% vs. post 54%; P < .0001) whereas overall CT use declined by 15% post GEP funding (pre 85% vs. post 70%; P = .01) and by additional 16% post TAILORx (pre 70% vs. post 54%; P = .01). Although not significant, OFS use increased by 8% post SOFT/TEXT (pre 13% vs. post 21%; P = .08). In subgroup analyses, post TAILORx was associated with a significant reduction in CT use of 19.5% in non-GEP tested women (pre 85% vs. post 65% P = .01) and non-significant increase in CT use of 6% in RS tested women (pre 40% vs. post 46%; P = .61) mainly driven by high mid range RS 21-25 and lower high range RS 26-30. There was no significant change in OFS use in non-CT treated women post SOFT/TEXT (Pre 5.3% vs. Post 8%, P = .68) whereas OFS use increased by 15% in women treated with CT post SOFT/TEXT (pre 15% vs. post 30%; P = .01). Conclusions: Public GEP funding and TAILORx led to widespread adoption of GEP and real-world decline in CT use in women 40 years of age or younger diagnosed with HR+, HER2-, LN- BC in Alberta. SOFT/TEXT led to real-world incline in OFS use in those treated with CT but adoption remained suboptimal.

Adjuvant therapy for HR+/HER2– early-stage breast cancer (EBC): Changes in practice patterns among community oncologists in Brazil.

e18820 Background: The management of HR+/HER2– early breast cancer (EBC) has changed significantly, with more patients are being classified as low-risk and spared adjuvant chemotherapy (CT) and de-escalating endocrine therapy (ET); on the other hand, other patient groups have experienced treatment escalation, such as high-risk premenopausal women. This study aims to assess practice patterns and real-world data for patients with HR+/HER2- EBC treated in Brazil's largest network of community oncology practices. Methods: Retrospective real-world study from the Oncoclínicas with longitudinal EHR data merged in a platform where structured variables were integrated with unstructured elements from physician notes using technology-based abstraction and expert human curators that follow mCODE standards and predefined ontology. Index data was EBC diagnosis date, and we restricted the study to patients diagnosed between Jan 2017 and Jun 2022, with comparative analysis of adjuvant CT/ET practice trends in 2017-2019 versus 2020-2022. Results: From over 30k patients with breast cancer in Oncoclínicas Database, 19k had HR+/HER2– EBC, 12k were treated in high-volume clinics, and 2,988 were selected for the study due to data accessibility in the pre-specific observation period. Stage distribution: I in 45%, II in 37%, and III in 18%. Pre-menopausal status at diagnosis: 22%. Less than 5% of the study population had access to breast cancer prognostic risk scores. The disease-free survival rate in the entire cohort was 87% (CI95% 86-89) at 2 years and 74% (CI95% 70-78) at 5 years. Overall, we observed a decrease in adjuvant CT use from 51% during 2017-2019 to 41% during 2020-2022. In pre- menopausal patients, CT use reduced from 68% in stage I during 2017-2019 to 41% during 2020-2022; for stage II or III, the reduction was less noticeable (83% in 2017-2019 to 75% in 2020-2022). In post-menopausal patients, CT use reduced from 36% in stage I during 2017-2019 to 18% during 2020-2022; while it remained stable in stage II or III (55% in 2017-2019 versus 52% in 2020-2022). Concerning ET, there were no evident changes in treatment practice. In pre-menopausal, tamoxifen alone was the first option in 90% with stage I and in 64% with stage II or III, with the stability over the years. In post-menopausal, aromatase inhibitors were the first option in 61% with stage I, 70% with stage II and 77% with stage III, with the stability over the years. Conclusions: We perceived a reduction in chemotherapy use in HR+/HER2– stage I breast cancer over time. Reasons for treatment selection must be investigated further, including other prognostic factors, but might be related to greater physician confidence in avoiding CT and access to genomic signatures. There were no significant changes in patterns of adjuvant ET, with most pre- and postmenopausal patients receiving tamoxifen alone and an aromatase inhibitor respectively.

Impact of TAILORx on chemotherapy prescribing and 21-gene recurrence score-guided treatment costs in a population-based cohort of patients with breast cancer.

The trial assigning individualized options for treatment (Rx) (TAILORx) confirmed the predictive value of the 21-gene recurrence score (RS) assay in hormone receptor (HR)-positive, HER2-negative, node-negative breast cancer and established thresholds for chemotherapy benefit in younger and older patients. Real-world chemotherapy use and RS-guided treatment costs in British Columbia post-TAILORx were examined. The authors assembled 3 cohorts of HR-positive, HER2-negative, node-negative patients with breast cancer defined by diagnosis: before RS funding (cohort 1 [C1]: January 2013-December 2013), after introduction of public RS funding (cohort 2 [C2]: July 2015-June 2016), and after TAILORx results (cohort 3 [C3]: July 2018-June 2019). Chemotherapy use was compared between cohorts by age and RS. Budgetary impacts of RS testing on chemotherapy costs were evaluated pre- and post-TAILORx. Among the 2066 patients included, chemotherapy use declined by 19% after RS funding was introduced and by an additional 23% after TAILORx publication (P = .001). Reduction in chemotherapy use was significant for RS 11-20 tumors (C3 vs C2, P = .004). There was no significant change in chemotherapy use in patients >50 years old (C2:12% vs C3:10%, P = .22). RS testing was associated with higher cost savings post-TAILORx, except in patients 70 to 80 years old, where testing led to excess costs when adjusting for the low rate of RS-concordant chemotherapy prescribed. TAILORx has had population-based impacts on chemotherapy prescribing in intermediate RS tumors and patients ≤50 years old. The lower clinical use of RS and increased spending in patients 70-80 years old highlights the importance of careful selection of older candidates for high-cost genomic testing. The 21-gene recurrence score (RS) test helps predict whether patients with hormone-positive, HER2-negative, lymph node-negative breast cancer are likely to benefit from chemotherapy. The recent trial assigning individualized options for treatment (Rx) (TAILORx) found that patients with intermediate RS tumors did not benefit from chemotherapy. The authors assessed whether TAILORx results translated to real-world changes in chemotherapy prescribing patterns. In this study, chemotherapy use decreased by 23% after TAILORx, with the greatest reductions seen among intermediate RS tumors and younger patients. In contrast, RS testing had lower clinical value and increased treatment costs in elderly patients, which requires further study to ensure optimal care for this age group.

Impact of the 21-Gene Recurrence Score Assay on the Treatment of Estrogen Receptor-Positive, HER2-Negative, Breast Cancer Patients With 1-3 Positive Nodes: A Prospective Clinical Utility Study

PurposeThe use of the 21-gene Recurrence Score (RS) assay is emerging in node-positive estrogen receptor (ER)+ HER2-negative breast cancer (BC), particularly as initial data from the RxPONDER trial are now available. We investigated the impact of the RS result on adjuvant treatment decisions in such patients. Patients and MethodsThis prospective, multi-center study enrolled patients with ER+, HER2-negative BC and 1 to 3 positive nodes (microscopic [N1mi] or macroscopic [N1]). Treating oncologists documented treatment recommendations/plan before and after knowing the RS result. Sample size was determined assuming an overall treatment change rate (from chemohormonal therapy [CHT] to hormone therapy [HT] and vice-versa) of ≥30%. ResultsThe study included 84 patients across 5 regional cancer centers, of whom 82 underwent 21-gene testing (77%, N1 disease; 63% grade 2 tumors). Of the RS-tested patients, 60%, 33%, and 7% had RS 0 to 17, 18 to 30, and 31 to 100, respectively. In 43 patients (52%), treatment changed post-RS: 40 patients (49%) from CHT to HT and 3 patients (4%) from HT to CHT. The net change was a 45% reduction in chemotherapy use. Treatment recommendation changes were consistent with the RS result. In RS 0 to 17 patients, the only documented change was from CHT to HT (27 patients). In RS 18-30 patients, change was noted in both directions (CHT-to-HT, 13 patients; HT-to-CHT, 3 patients). No treatment change was reported for the RS 31 to 100 patients, all of whom were recommended CHT pre-testing. ConclusionOur results support the clinical utility of the RS assay in ER+ HER2-negative BC with 1 to 3 positive nodes.

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. 963 pts. Mean age is 56years. Mean tumour size is 1.7cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of €4 million in treatment costs. Deducting assay costs, savings of €1.9 million were achieved. Over the 8years of the study, a 62.5% reduction in CT use was achieved with savings of over €1,900,000.

Abstract PS4-23: An analysis of the clinical and economic impact of the 21-gene recurrence score (RS) in invasive lobular early-stage breast cancer (ESBC) in Ireland

Abstract Background: The use of the 21-gene recurrence score assay (RS) has reduced chemotherapy (CT) administration in patients with hormone receptor (HR)-positive, HER-2 negative, lymph-node negative, early stage breast cancer (ESBC). Invasive lobular carcinoma (ILC) accounts for up to 15% of all breast cancers. This study uses real world data to assess (1) the effect of RS testing on treatment decision making in patients with ILC and (2) the economic benefit of testing in this subgroup. Methods: From October 2011 to February 2019, a retrospective, cross-sectional, observational study was conducted on HR+, HER-2 negative, lymph-node negative, ESBC patients with ILC who had RS testing in Ireland. For the decision impact analysis, a survey of Irish breast medical oncologists presumed that, without RS testing, CT would be recommended to patients with histological grade (G) 2 and 3 tumours and not for G1 tumours. In accordance with TAILOR-x results, patients were classified overall as low risk (RS≤25) and high risk (RS>25) and patients ≤50 years old were low risk (RS 0-15), intermediate risk (RS 16-25), and high risk (RS>25). Data were collected from electronic patient records. Descriptive statistics were used. Cost data were obtained from the National Healthcare Pricing Regulatory Authority. The economic analysis was adjusted for changing treatment and assay costs over the study period. Results: 166 patients with ILC were identified. Mean age was 59 years. Mean tumour size was 2.3cm (range 0.7-5.8). The majority had G2 tumors (n=152, 92%) with a small number of G3 (n=7, 4%) and G1 (n=7,4%). Overall, 153 patients (92.2%) had a low RS (≤25), 12 (7.2%) had high RS (>25), and 1(0.6%) was unknown. All 12 patients with RS>25 had G2 tumours, 6/12 (50%) had tumour size >3cm, 4(33.3%) were PR+ and 8(66.7%) were PR negative. In 29/166 (17.5%) patients, aged ≤50 at diagnosis, RS was ≤15 in 16(55%), 16-20 in 6(21%), 21-25 in 5(17%), >25 in 1(3.5%) and unknown in 1(3.5%). The majority of these patients (27, 93%) had G2 tumours, 1 had G1 and 1 had G3. Post RS testing 124 patients (74.5%) had a change in CT recommendation; all from CT to hormone therapy. In total, only 35 patients (21%) received CT. In this group, RS was 0-15 in 3(9%), RS 16-25 in 19(54%), RS >25 in 12 (34%) and unknown in 1(3%). Eight of 35 patients (23%) were aged ≤50. The most common CT regimen administered was docetaxel plus cyclophosphamide (TC). RS testing achieved a 78% reduction in chemotherapy use. This resulted in savings of €900,000 in treatment costs. With the incorporation of the assay cost, the net savings totalled approximately €400,000. Conclusions: Ireland was the first public health care system to reimburse the 21-gene recurrence score assay in Europe. There is limited evidence demonstrating the benefits of RS in ILC. In our study, the use of the test has resulted in a 78% reduction in chemotherapy use in an Irish ILC patient population and a substantial cost saving (greater than €400,000) to the Irish Healthcare System. Citation Format: Mehala Tharmabala, Lynda McSorley, Fathiya Al Rahbi, Evoy Denis, James G Geraghty, Rothwell Jane, Damian McCartan, Enda McDermott, Maccon M Keane, John Kennedy, Seamus O'Reilly, Steve Millen, John Crown, Lilian Mary Smyth, Catherine Margaret Kelly, Prichard Ruth, Cecily Quinn, Janice M Walshe. An analysis of the clinical and economic impact of the 21-gene recurrence score (RS) in invasive lobular early-stage breast cancer (ESBC) in Ireland [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-23.

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

540 Background: Treatment of hormone receptor positive (HR+) ESBC is evolving. The use of chemotherapy (CT) is declining with use of the 21-gene RS assay. This validated tool predicts the likelihood of adjuvant CT benefit in HR+ ESBC. Results from the TAILOR-x study suggest up to 70% of HR+ node negative ESBC patients (pts) may avoid CT with RS ≤25. Our objectives were to assess the clinical and economic impact of RS testing on treatment decisions using real-world data. Methods: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ node negative ESBC pts who had RS testing in Ireland. A survey of Irish breast medical oncologists provided the assumption for the decision impact analysis that grade (G) 1 pts would not receive CT pre RS testing and G2/3 pts would receive CT. Using TAILOR-x results, pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Data was collected via electronic patient records. Descriptive statistics were used. Cost data was obtained via the National Healthcare Pricing Regulatory Authority. The economic analysis was adjusted for changing treatment and assay costs over the study period. Results: 963pts were identified. Mean age 56 years. Mean tumour size 1.87cm. 114 (11.8%), 636(66%), 211(22%), 2(0.2%) pts had G1, G2, G3 and unknown G respectively (resp). 797pts (82.8%) had low RS, 159 (16.5%) had high RS, and 7pts(0.7%) unknown RS. 251pts(26%) were aged < 51 at diagnosis. Of these, 45(17.9%), 145(57.8%), 58(23%), 3(1.2) had G1, G2, G3 and unknown G resp. 208pts(82.9%) had RS ≤ 25, 39pts(15.5%) had RS > 25 and 4pts(1.6%) unknown RS. In the RS ≤ 25 group, 111pts(44%) had RS 0-15, 59(23.5%) had RS16-20, and 38(15.1%) had RS21-25. Post RS testing 595pts(61.8%) had a change in CT decision; 586 changed to hormone therapy (HT) alone, and 9 from HT to CT. In total, 227pts(23.5%) received CT, and 3pts(0.3%) declined. Of pts treated with CT; 9(4%) had RS 0-15, 89(39.2%) had RS16-25, 129(56.8%) had RS > 25. The most common CT regimen was docetaxel and cyclophosphamide(TC), administered to 121pts(53%). RS assay use achieved a 69% change in treatment decision among G2/3 pts and a net 61% reduction in CT use. This resulted in savings of over €4 million in treatment costs. Deducting the assay cost, net savings of over one million euro was achieved. Conclusions: Ireland was the first public healthcare system to approve reimbursement for RS testing. Over the 8 year period of the study, a net 61% reduction in CT use in Irish pts with HR+ ESBC was achieved with conservative net savings of over €1,000,000.

Impact of immune checkpoint and BRAF inhibitors on the incidence of second primary malignancies (SPM) in melanoma.

12061 Background: Prior studies have shown an increased risk of SPM in melanoma, however there is limited data on the incidence of SPM following the 2011 approvals of immune checkpoint (ipilimumab) and BRAF (vemurafenib) inhibitors, which have become standard of care. We present data comparing SPM rates before and after introduction of these agents for advanced cutaneous melanoma. Methods: Adult melanoma patients with regional or distant metastases were identified from SEER-18 database and divided into cohorts: 2005-2010 and 2011-2016. SPM was defined as tumors diagnosed ≥6 months from diagnosis of the primary cancer. SEER*stat was used to calculate SPM by multiple primary standardized incidence ratio based on observed (O) and expected (E) cases. The expected numbers of new cancers of specific types were estimated by assuming that incidence rates for new primary tumors corresponded to sex, age, and calendar time–specific SEER rates for similar invasive primary cancers and applying those rates to the accumulated person-years (PYR) of observation. Excess absolute risk (EAR) of malignancy per 10,000 PYR at risk was calculated as ([O − E]/PYR) × 10,000. Results: As shown in the table, from before 2005-2010, 421 of 7991 patients (5.2%) with advanced melanoma had 444 SPM (O/E ratio 2.2, 95% CI 1.9-2.4, P < 0.0001, EAR 157). In comparison, from 2011-2016, 527 of 9341 patients (5.6%) developed 584 SPM (O/E ratio 2.5, 95% CI 2.3-2.7, P < 0.0001, EAR 193). Incidence of AML, myeloma, and pancreatic cancer increased in 2005-2010, while soft tissue malignancies increased from 2011-2016. The incidence of thyroid, brain, and small bowel tumors increased in both groups from 2005-2016. Conclusions: There is a distinct pattern as well as increased latency of SPM in patients with advanced melanoma in the era of immune checkpoint and BRAF inhibitors. We speculate that reduction in chemotherapy use, augmentation of immunosurveillance, and inhibition of oncogenic pathways may impact the pathogenesis of SPM. [Table: see text]

The Warwick Experience of the Oncotype DX® Breast Recurrence Score® Assay as a Predictor of Chemotherapy Administration

Introduction: Oncotype DX® analyses the expression of 21 genes within tumour tissue to determine a Recurrence Score® (RS). RS is a marker of risk for distant recurrence in oestrogen receptor-positive early breast cancer, allowing patient-specific benefit of chemotherapy to be evaluated. Our aim was to determine whether the introduction of Oncotype DX led to a net reduction in chemotherapy use. Methods: Consecutive patients that underwent Oncotype DX at Warwick Hospital were reviewed. Patients were anonymised and re-discussed at a multidisciplinary team meeting (MDM; without RS), and treatment recommendations were recorded. This was compared to the original MDM outcome (recommendations made with RS). Differences were analysed using Wilcoxon signed-rank test. Results: 67 patients were identified. Proportions of high, intermediate and low risk were 28, 33 and 39% (n = 19/22/26), respectively. Without RS, 56 (84%) patients were recommended for chemotherapy and 3 were not. The remaining 8 patients were deemed borderline for requiring chemotherapy and referred for discussion with an oncologist. With availability of RS, 34 (50%) patients were recommended for chemotherapy, and 24 (43%) patients were spared chemotherapy (p < 0.0005). The net reduction in chemotherapy was 33%. Conclusion: There has been a significant reduction in chemotherapy usage in patients at Warwick since the introduction of Oncotype DX.

Clinical utility of Oncotype DX in early stage colon cancer.

e15076 Background: With the advent of colon cancer screening, patients with early stage colon cancer will be more common in our clinics. The evidence supporting the absolute benefit of chemotherapy in resected Stage II and (to a lesser extent) Stage IIIA disease is poor. Not all patients benefit from chemotherapy and toxicity is a problem. There is a need for validated biomarkers to assess individual patient recurrence risk and discriminate absolute treatment benefit. Several studies have validated the role of the OncotypeDX testing in Stage II/IIIA disease. Our objective is to characterize whether this test impacted oncologists’ decisions in treating patients with Stage II/IIIA in the adjuvant setting. Methods: :The Onco typeDX assay is a multi-gene reverse-transcriptase-polymerase-chain-reaction test that analyses the expression of 12 genes involved in key biologic pathways in colon cancer. Stage II and Stage IIIA colon cancers were studied in affiliated hospitals of our region in southwest Ireland. All data collected is prospective and each colon cancer was assigned a recurrence risk score. Oncologists were blinded to this score and the decision to prescribe adjuvant chemotherapy was recorded. After un-blinding the score, a second decision was recorded and comparisons made. Results: :From August 2015 to September 2016, 70 patients have been recruited with M: F of 2:1. Median age at diagnosis was 65 years. Most patients (80%) had stage II disease, 11 of whom had mismatch repair loss on IHC. OncotypeDX testing has been carried out and reported for 59 patients (85%), MMR intact. Recurrence scores: &lt; 30 in 46 patients (77.9%), 30-40 in 10 patients, and &gt; 40 in 3 patients. The treatment plan was altered in 16 patients (27%), of whom 12 patients (20%) received none or less intense chemotherapy. Conclusions: We have shown that the decision to prescribe adjuvant chemotherapy was changed in 27% of patients. This test has helped to define patients with low scores, where chemotherapy-related toxicity is a concern especially in older patients. Absolute benefit of adjuvant chemotherapy versus the risk of toxicity should be discussed. . Hospital managers may be interested in cost savings due to a reduction in chemotherapy use.

The influence of 21-gene recurrence score assay on chemotherapy use in a population-based sample of breast cancer patients.

To quantify the influence of RS assay on changing chemotherapy plans in a general practice setting using causal inference methods. We surveyed 3880 newly diagnosed breast cancer patients in Los Angeles and Georgia in 2013-14. We used inverse propensity weighting and multiple imputations to derive complete information for each patient about treatment status with and without testing. A half of the 1545 women eligible for testing (ER+ or PR+, HER2-, and stage I-II) received RS. We estimate that 30% (95% confidence interval (CI) 10-49%) of patients would have changed their treatment selections after RS assay, with 10% (CI 0-20%) being encouraged to undergo chemotherapy and 20% (CI 10-30%) being discouraged from chemotherapy. The subgroups whose treatment selections would be changed the most by RS were patients with positive nodes (44%; CI 24-64%), larger tumor (43% for tumor size >2cm; CI 23-62%), or younger age (41% for <50years, CI 23-58%). The assay was associated with a net reduction in chemotherapy use by 10% (CI 4-16%). The reduction was much greater for women with positive nodes (31%; CI 21-41%), larger tumor (30% for tumor size >2cm; CI 22-38%), or younger age (22% for <50years; CI 9-35%). RS substantially changed chemotherapy treatment selections with the largest influence among patients with less favorable pre-test prognosis. Whether this is optimal awaits the results of clinical trials addressing the utility of RS testing in selected subgroups.

Economic impact of 21-gene recurrence score testing on early-stage breast cancer in Ireland

The 21-gene test is a validated multi-gene diagnostic test that predicts chemotherapy (CT) benefit in oestrogen receptor positive (ER+), lymph node-negative (N0) breast cancer (BC) patients (pts). Ireland was the first public health care system to reimburse this test in Europe. Study objectives were to assess the impact of this test on decision-making and to analyse the economic impact of testing. Between October 2011 and February 2013, a national, retrospective, cross-sectional observational study of ER+, N0 BC pts tested with the 21-gene test was conducted. Surveyed breast medical oncologists, provided the assumption for the decision impact analysis that grade (G) 1 pts would not have received CT before testing and G2/3 pts would have received CT before testing. Descriptive statistical analyses were performed. 592 pts were identified; Low, intermediate and high recurrence score were identified in 53, 36 and 10 % pts, respectively. 384 (70 %) pts had G2, 129 (22 %) G3 and 76 (13 %) G1 tumours. Post testing, 345 pts (59 %) experienced a change in CT decision; 339 changed to hormone therapy alone and 6 advised to receive CT. 172 (30 %) pts received CT, 12 (3.9 %) of pts with low scores, 108 (50.9 %) of intermediate risk and 50 (90.9 %) of pts with high risk scores. Net reduction in CT use was 58 % and net savings achieved were €793,565. Since public reimbursement, the introduction of the 21-gene test has resulted in a significant reduction in chemotherapy administration and cost savings for the Irish public healthcare system.

Prospective Clinical Utility Study of the Use of the 21-Gene Assay in Adjuvant Clinical Decision Making in Women With Estrogen Receptor-Positive Early Invasive Breast Cancer: Results From the SWITCH Study.

The 21-gene Oncotype DX Recurrence Score assay is a validated assay to help decide the appropriate treatment for estrogen receptor-positive (ER+), early-stage breast cancer (EBC) in the adjuvant setting. The choice of adjuvant treatments might vary considerably in different countries according to various treatment guidelines. This prospective multicenter study is the first to assess the impact of the Oncotype DX assay in the French clinical setting. A total of 100 patients with ER+, human epidermal growth factor receptor 2-negative EBC, and node-negative (pN0) disease or micrometastases in up to 3 lymph nodes (pN1mi) were enrolled. Treatment recommendations, physicians' confidence before and after knowing the Recurrence Score value, and physicians' perception of the assay were recorded. Of the 100 patients, 95 were evaluable (83 pN0, 12 pN1mi). Treatment recommendations changed in 37% of patients, predominantly from chemoendocrine to endocrine treatment alone. The proportion of patients recommended chemotherapy decreased from 52% pretest to 25% post-test. Of patients originally recommended chemotherapy, 61% were recommended endocrine treatment alone after receiving the Recurrence Score result. For both pN0 and pN1mi patients, post-test recommendations appeared to follow the Recurrence Score result for low and high values. Physicians' confidence improved significantly. These are the first prospective data on the impact of the Oncotype DX assay on adjuvant treatment decisions in France. Using the assay was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. These data are consistent with those presented from European and non-European studies.

A comparison of chemotherapy use in stage IV pancreatic cancer.

257 Background: Palliative chemotherapy is the standard of care for stage IV pancreatic cancer patients (SFPC). Methods: This study compares the amount of chemotherapy given for SFPC across insurance types using the National Cancer Database (NCDB), which contains 70% of U.S. cancer cases. Results: The NCDB reported 115,512 patients diagnosed with SFPC from 2000 to 2009. Overall, 38.3% of SFPC patients received chemotherapy. The VAH (28.3%) and Medicare (29.7%) provided significantly less chemotherapy to SFPC patients as compared to Managed Care (48.2%), Private Insurance (46.7%), Tricare/Military (42.8%), Medicaid (37.8%), Medicare Plus Supplement (35.5%), and Uninsured (34.4%). From 2000 to 2009, the rate of chemotherapy for SFPC increased for both VAH (22.9% to 34.3%) and non-VAH (31.1% to 44.1%). At time of diagnosis, the percent of patients less than 60 at the VAH was 32%, non-VAH was 25.5% and Medicare was 7%. From age 20 to 59, the rate of chemo was stable at approximately 49%, but each successive decade demonstrated a marked reduction in use of chemotherapy (from 44% for 60 to 69 years of age to 21% for 80 to 89 and 5% for &gt;90). The VAH PC population diagnosed with PC included 71.1% whites (W), 21.1% blacks (B), 4.8% Hispanics (H), 0.8% Asian-Pacific Islander (API), and 0.6% Native American (NA). Among all insurance types, only Medicaid (25%* B, 14%* H, 6%* API) and Uninsured (20% B, 15%* H, 4%* API) had a greater percentage of minorities. Compared to the average of all patients treated for SFPC (38.3%), blacks (34.7%*) and Hispanics (35.7%*) received less chemotherapy and whites received more (39.1%*). Conclusions: This is the largest study to analyze the use of chemotherapy in stage IV pancreatic cancer. Patients treated within the VAH were less likely to receive chemotherapy compared to all other patients except those with Medicare, who tend to be older at time of diagnosis. As age increases above 59, chemotherapy treatment for SFPC decreases. VAH patients receive less chemotherapy than Medicaid and Uninsured patients, though Medicaid and Uninsured have a greater percentage of minorities, who tend to get less chemotherapy for SFPC.

252PD - Meta-Analysis of Prospective European Studies Assessing the Impact of Using The 21-Gene Recurrence Score Assay on Clinical Decision Making in Women With Er-Positive, Her2-Negative Early Stage Breast Cancer

ABSTRACT Background The Oncotype DX® Recurrence Score is a validated assay to help inform the appropriate treatment of estrogen receptor-positive (ER+), early stage breast cancer. Adjuvant treatment traditions vary significantly among different countries. Prospective studies assessing the impact of the Oncotype DX test on adjuvant treatment decisions have been performed in several European countries. This is a meta-analysis of these studies. Methods Four prospective studies assessing the impact of using the Recurrence Score result on clinical decision making in patients with node negative and pN1 (mi) disease were identified. Node positive patients were excluded. The identified studies had a similar study design with consecutive patients and treatment recommendations before and after having the Recurrence Score results were recorded. In three of the studies, medical oncologists completed questionnaires regarding their confidence in their recommendation before and after knowing the patient's Recurrence Score result. The final results of the studies in Germany, Spain and the UK have been presented and final data from the French study will be presented at ASCO 2012. Results A total of 589 patients with node negative or pN1 (mi) ER pos HER2 negative early breast cancer were included in the four identified studies. Overall, 45% (range 36-52%) of patients in these studies were recommended chemo-endocrine and 55% endocrine treatment alone. After having the Recurrence Score result, 47% (range 38-60%) of patients recommended chemotherapy were changed to endocrine treatment alone and 17% (range 11-22%) of those recommended endocrine treatment alone were recommended chemo-endocrine treatment. There was a significant improvement in physician confidence in treatment recommendations when using the assay. Conclusion Using Oncotype DX® is associated with a significant change in treatment decisions and a reduction in chemotherapy use in studied European countries despite differences in therapeutic traditions. The consistency of the results from different countries underlines the tests utility. Disclosure J. Albanell: Participated advisory board (Genomic Health). S. Holt: Participated as a speaker, and in advisory board for Genomic Health. J. Gligorov: Has participated as speaker for Genomic Health. W. Eiermann: Participated as speaker and in advisory board for Genomic Health. C. Svedman: Employee and stocks in Genomic Health.

Prospective study of the impact of using the 21-gene recurrence score assay on clinical decision making in women with estrogen receptor-positive, HER2-negative, early-stage breast cancer in France.

568^ Background: The 21-gene Oncotype DX Recurrence Score (RS) is a validated assay to help inform the appropriate treatment of estrogen receptor-positive (ER+), early stage breast cancer in the adjuvant setting. Treatment traditions regarding choice of adjuvant treatment vary significantly in different countries. This prospective multicenter study is the first to assess the impact of using the Oncotype DX assay in the French clinical setting. Methods: A total of 100 consecutive patients with ER+, HER2-negative, node negative or pN1 (mi) breast cancer were enrolled. Overall treatment recommendation change, change from chemoendocrine to endocrine alone and change from endocrine alone to chemoendocrine treatment were recorded. Medical oncologists completed questionnaires regarding their confidence in their recommendation before and after knowing the patient’s RS. A preliminary analysis was conducted on the first 92 evaluable patients with data available at the time of abstract submission. Final data will be presented at the meeting. Results: Prior to Oncotype DX 49% of patients were recommended chemoendocrine treatment and 51% endocrine treatment alone. After having the RS, 26% were recommended chemoendocrine treatment and 74% endocrine treatment alone. The overall reduction in chemotherapy recommendation from 49% to 26% was significant (p&lt;0.001). Of patients originally recommended chemoendocrine treatment, 58% were changed to endocrine treatment alone after having the RS. Of patients originally recommended endocrine treatment, 11% were changed to chemoendocrine treatment after receiving the RS. There was a significant improvement in physician confidence in treatment recommendations (p=0.002) when using Oncotype DX. Conclusions: These are the first prospective data regarding the impact of using Oncotype DX in France. Using Oncotype DX was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. The data are consistent with those presented from Germany, Spain, the UK and the US.

Cost-effectiveness of targeting chemotherapy with the 70-gene prognostic signature in early-stage breast cancer (ESBC) patients

6570 Background: The 70-gene microarray test (MammaPrint) has been shown to provide additional prognostic information to clinicopathologic risk assessment for women ESBC; however, the cost-effectiveness of this strategy is not well understood. Methods: The objective of this analysis was to estimate the incremental benefits, costs, and cost-effectiveness of the treatments guided by the 70-gene signature versus Adjuvant! Software (AS) to decide on the use of adjuvant chemotherapy for women ≤61 years with lymph node negative, HER-2 negative ESBC with estrogen receptor (ER) positive or negative disease. A Markov model with a lifetime horizon and three health states (alive without recurrence, death from cancer and death from other causes) was constructed using TreeAge Pro software. Risk classification and patient outcomes data were based on a multi-center 70-gene signature validation study. Efficacy of chemotherapy derived from published meta-analysis of clinical trials. Costs and health utilities were obtained from the literature. Costs and benefits were discounted 3%/year. Results: Compared to AS, the 70-gene signature strategy resulted in 35% of patients being reassigned to a different risk classification and avoided chemotherapy in 9% of patients. In the base case, the 70-gene signature strategy was cost neutral (lifetime costs per patient: $178,811 versus $178,893 for the 70-gene signature and AS strategy). Moreover the 70-gene signature strategy was associated with an increase of 0.13 life years (LYs) and 0.16 quality adjusted life years (QALYs). The model results were sensitive to the cost of 70-gene signature test, cost of adjuvant chemotherapy, and relative risk reduction associated with chemotherapy; however, the 70-gene strategy remained cost-effective across a wide range of assumptions. Conclusions: In this analysis, the 70-gene signature was associated with a reduction in chemotherapy use and an increase in life expectancy. The 70-gene signature appears to be a cost-effective strategy for obtaining additional information to guide the decision to use adjuvant chemotherapy in patients with lymph node negative ESBC. [Table: see text]