Steven Sugarman

HSP90 Inhibition Is Effective in Breast Cancer: A Phase II Trial of Tanespimycin (17-AAG) Plus Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer Progressing on Trastuzumab

Purpose: HSP90 is a chaperone protein required for the stability of a variety of client proteins. 17-Demethoxygeldanamycin (17-AAG) is a natural product that binds to HSP90 and inhibits its activity, thereby inducing the degradation of these clients. In preclinical studies, HER2 is one of the most sensitive known client proteins of 17-AAG. On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer. Experimental Design: We enrolled patients with metastatic HER2+ breast cancer whose disease had previously progressed on trastuzumab. All patients received weekly treatment with tanespimycin at 450 mg/m2 intravenously and trastuzumab at a conventional dose. Therapy was continued until disease progression. The primary endpoint was response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results: Thirty-one patients were enrolled with a median age of 53 years and a median Karnofsky performance status (KPS) of 90%. The most common toxicities, largely grade 1, were diarrhea, fatigue, nausea, and headache. The overall response rate was 22%, the clinical benefit rate [complete response + partial response + stable disease] was 59%, the median progression-free survival was 6 months (95% CI: 4–9), and the median overall survival was 17 months (95% CI: 16–28). Conclusions: This is the first phase II study to definitively show RECIST-defined responses for 17-AAG in solid tumors. Tanespimycin plus trastuzumab has significant anticancer activity in patients with HER2-positive, metastatic breast cancer previously progressing on trastuzumab. Further research exploring this therapeutic interaction and the activity of HSP90 inhibitors is clearly warranted. Clin Cancer Res; 17(15); 5132–9. ©2011 AACR.

A Phase II Open-Label Study of Ganetespib, a Novel Heat Shock Protein 90 Inhibitor for Patients With Metastatic Breast Cancer

BACKGROUNDnGanetespib is a small molecule, nongeldanamycin HSP90 inhibitor with potent inhibitory effects on HSP90-dependent oncoproteins of relevance to breast cancer pathogenesis. We therefore tested ganetespib in an unselected cohort of patients with MBC.nnnPATIENTS AND METHODSnPatients were treated with single agent ganetespib at 200 mg/m(2) once weekly for 3 weeks, on a 28-day cycle. Therapy was continued until disease progression. The primary end point was ORR using Reponse Evaluation Criteria in Solid Tumors version 1.1.nnnRESULTSnTwenty-two patients were enrolled with a median age of 51(range, 38-70) years and a median Eastern Cooperative Oncology Group performance status of 0 (range, 0-1). Most patients had at least 2 previous lines of chemotherapy in the metastatic setting. Most common toxicities, largely grade 1/2, were diarrhea, fatigue, nausea, and hypersensitivity reaction. The ORR in this unselected population was 9%, with all responses coming from the subset of patients with HER2-positive MBC (2/13;xa015%). One patient with TNBC had objective tumor regression in the lung metastases. The clinical benefit rate (complete responsexa0+ partial responsexa0+ stable disease > 6 months) was 9%, median progression-free survival was 7xa0weeks (95% confidence interval [CI], 7-19), and median overall survival was 46 weeks (95% CI, 27-not applicable).nnnCONCLUSIONnThe study did not meet the prespecified criteria for ORR in the first stage of the Simon 2-stage model in this heavily pretreated unselected population of MBC. However, activity was observed in trastuzumab-refractory HER2-positive and TNBC. Ganetespib was well tolerated and responses in more targeted populations harboring specific HSP90-dependent oncoproteins justifies its further study, particularly as part of rational combinations.

A pilot study of dose-dense adjuvant paclitaxel without growth factor support for women with early breast carcinoma

Purpose Granulocyte-colony stimulating factor (G-CSF) was used in CALGB 9741 to support dose-dense sequential chemotherapy with doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) (Citron et al. J Clin Oncol 21:1431–1439, 2003). However, myelosuppression is not known to be dose or schedule limiting for paclitaxel. We therefore conducted this trial to determine the need for routine G-CSF, using the pegylated product (pG-CSF), support during the paclitaxel component of dose-dense sequential chemotherapy in women with early stage breast carcinoma (BC). Patients and methods Eligible patients received dose-dense chemotherapy consisting of four cycles of AC followed by four cycles of P at two week intervals. pG-CSF (NeulastaTM) was administered after each of four cycles of AC but was held after P. Planned enrollment was 59 pts. Results Of the first 15 patients, nine completed therapy without delays due to neutropenia but 6 (40%) did not, leading to implementation of the pre-specified early termination rule. Overall, 85% of P doses were successfully delivered on time. The mean treatment delay for the entire group due to neutropenia was 0.75xa0days. There was no significant correlation between neutropenia and prior WBC, ANC, or concurrent treatment with trastuzumab. Pts with neutropenia tended to be younger (Mean age 43.5) and have a lower BSA (1.65xa0m2). There were no febrile episodes due to omission of pG-CSF. Conclusion When paclitaxel is administered in a dose-dense fashion without growth factor support brief treatment delays are common. Further study is needed to identify the minimal pG-CSF administration that will avoid treatment delays.

Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2‐Positive Early Stage Breast Cancer: A Single Center Experience

OBJECTIVESnTrastuzumab (H) and pertuzumab (P) with standard chemotherapy is approved for use in the neoadjuvant setting for human epidermal growth receptor 2 -positive patients. A retrospective analysis was performed of patients treated with dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T), trastuzumab, and pertuzumab (THP) in the neoadjuvant setting. Here, the pathologic complete response (pCR) rates are reported.nnnMETHODSnAn electronic medical record review was conducted of patients treated with HP-based therapy in the neoadjuvant setting from September 1, 2013, to March 1, 2015. Data on patient demographics, stage of breast cancer, pathology reports, surgical data, and information on systemic therapy were collected. The pCR was defined as total (tpCR, ypT0/is ypN0), German Breast Group (GBG) pCR (ypT0 ypN0), breast pCR (bpCR) with in situ disease (ypT0/is) and without in situ disease (ypT0), and explored axillary pCR (ypN0).nnnRESULTSnCharts from 66 patients were reviewed, and 57 patients were evaluable for pCR. Median age was 46 years (range 26-68 years). Median tumor size was 4 cm. Of 57 patients, 53 (93%) had operable breast cancer (T1-3, N0-1, M0). Three patients (5.3%) had locally advanced disease (T2-3, N2-3, M0 or T4a-c, any N, M0), and 1 (1.7%) had inflammatory breast cancer (T4d, any N, M0). Overall, 44 (77%) and 13 (23%) had hormone receptor (HR)-positive and negative diseases, respectively. Median numbers of cycles of neoadjuvant treatment were as follows: AC (4, range 1-4), T (4, range 1-4), trastuzumab (6, range 3-8), and pertuzumab (6, range 2-8). In these 57 patients, the rates of tpCR and bpCR with in situ disease were demonstrated in 41/57 (72%) patients, and the rates of GBG pCR and bpCR without in situ disease were found in 30/57 (53%) patients. Of 26 patients with biopsy-proven lymph nodal involvement, axillary pCR occurred in 22 (85%) patients.nnnCONCLUSIONnAt a single center, the tpCR and GBG pCR rates of dd AC followed by THP are high at 72% and 53%, respectively. The Oncologist 2017;22:139-143Implications for Practice: This is the first study describing the role of doxorubicin and cyclophosphamide followed by paclitaxel and dual anti-HER2 therapy with trastuzumab and pertuzumab (ACTHP) in patients with early stage HER2-positive breast cancer. Total (breast + lymph node) pathological complete remission (pCR) remission (ypT0/is ypN0) and German Breast Group pCR rates (ypT0/ ypN0) were high at 72% and 53%, respectively, with the ACTHP regimen. Rate of axillary clearance in patients with known axillary involvement was high at 85%, which may translate into less extensive axillary surgeries in this subset in the future.

Weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer: overall survival and updated progression-free survival results from a phase II study

We previously reported progression-free survival (PFS) results on a phase II trial of weekly paclitaxel, trastuzumab, and pertuzumab in patients with human epidermal growth factor receptor 2(HER2)–positive metastatic breast cancer (MBC) treated in the first- and second-line setting. Here, we report results for overall survival (OS) and updated PFS after an additional year of follow-up. Patients with HER2-positive MBC with 0–1 prior treatment were eligible. Treatment consisted of paclitaxel (80xa0mg/m2) weekly, and trastuzumab (loading dose 8xa0mg/kgxa0→xa06xa0mg/kg) and pertuzumab (loading dose 840xa0mgxa0→xa0420xa0mg) every 3xa0weeks, all given intravenously. Primary endpoint was 6-month PFS. Secondary endpoints included median PFS, 6-month and median OS. Evaluable patients received at least one full dose of treatment. From January 2011 to December 2013, 69 patients were enrolled: 51 (74xa0%) and 18 (26xa0%) treated in first- and second-line metastatic settings, respectively. As of July 1, 2015, the median follow-up was 33xa0months (range 3–49xa0months; 67 patients were evaluable for efficacy). The median OS was 44xa0months (95xa0% CI 37.5–NR) overall and 44xa0months (95xa0% CI 38.3–NR) and 37.5xa0months (95xa0% CI 30.3–NR) for patients with 0 and 1 prior metastatic treatment, respectively; 6-month OS was 98xa0% (95xa0% CI 90-1). The 6-month PFS was 86xa0% (95xa0% CI 75–93) overall and 89xa0% (95xa0% CI 76–95) and 78xa0% (95xa0% CI 51–91) for patients with 0 and 1 prior therapy, respectively; and median PFS was 21.4xa0months (95xa0% CI 14.1–NR) overall and 25.7xa0months (95xa0% CI 14.1–NR) and 16.9xa0months (95xa0% CI 8.5–NR) for patients with 0–1 prior treatment, respectively. Treatment was well tolerated. Updated analysis demonstrates that weekly paclitaxel, when added to trastuzumab and pertuzumab, is associated with a favorable OS and PFS and offers an alternative to docetaxel-based therapy. http://www.ClinicalTrials.gov NCT0127604

P1-17-08: A Phase II Trial of Ganetespib: Efficacy and Safety in Patients (pts) with Metastatic Breast Cancer (MBC).

Background: Heat shock protein 90 (Hsp90) is a molecular chaperone that maintains the stability of a number of key cellular oncoproteins (client proteins). When Hsp90 is inhibited, its client proteins undergo ubiquitination and degradation. HER2 is one of the most sensitive client proteins of Hsp90 and we have previously shown that tanespimycin, a geldanamycin-based Hsp90 inhibitor, is active in trastuzumab-refractory HER2+ MBC, with a RR of 22% and clinical benefit rate of 59%. Ganetespib is a synthetic, small molecule, IV administered, non-geldanamycin Hsp90 inhibitor which has broader inhibitory effects on oncoproteins with pre-clinical antitumor activity in more breast cancer (BC) subtypes, including triple negative breast cancer (TNBC). We therefore tested ganetespib in an unselected cohort of patients with advanced BC. Methods: Pts with locally advanced or MBC were treated with single agent ganetespib at 200mg/m2 once weekly for 3 weeks, on a 28 day cycle. The primary endpoint of the trial was overall response rate using RECIST 1.1. Pts with HER2+ BC were required to have received prior therapy with trastuzumab. No more than 3 lines of chemotherapy in the metastatic setting were permitted and there was no limit on prior lines of hormone therapy. Pts were evaluated for response after 2 cycles. The trial used a Simon two-stage design requiring at least 3 responses among the first 22 pts, to allow expansion to a total of 40 pts. Results: A total of 14 pts have been treated thus far with a median age of 45.3 years (36.6 to 59.1) and the following subtypes: 8 ER+/HER2+, 3 ER-/HER2+, 1 ER+/HER2− and 2 TNBC. Pts received a median of 1.84 cycles (0.33 to 4). The most common treatment-related AEs were Grade 1/2 and included the following: diarrhea (64%), fatigue (50%), nausea (35%), vomiting (14%), insomnia (14%) and hypersensitivity reactions (35%). The diarrhea had an early onset ( Conclusions: These data show activity for single agent ganetespib in different subtypes of breast cancer. Ganetespib was well tolerated, with expected gastrointestinal toxicity that was mild in nature and manageable in all patients. Accrual continues and we will present updated data at the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-17-08.

Dose Dense Cyclophosphamide, Methotrexate, Fluorouracil is Feasible at 14-Day Intervals: A Pilot Study of Every-14-Day Dosing as Adjuvant Therapy for Breast Cancer

PURPOSEnCyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule.nnnPATIENTS AND METHODSnThirty-eight patients with early-stage breast cancer were accrued from March 2008 through June 2008. They were treated every 14 days with C 600, M 40, F 600 (all mg/m2) with PEG-filgrastim (Neulasta®) support on day 2 of each cycle. The primary endpoint was tolerability using a Simons 2-stage optimal design. The design would effectively discriminate between true tolerability (as protocol-defined) rates of ≤ 60% and ≥ 80%.nnnRESULTSnThe median age was 52-years-old (range, 38-78 years of age). Twenty-nine of the 38 patients completed 8 cycles of CMF at 14-day intervals.nnnCONCLUSIONnDose-dense adjuvant CMF is tolerable and feasible at 14-day intervals with PEG-filgrastim support.

A Pilot Study of Dose-Dense Paclitaxel With Trastuzumab and Lapatinib for Node-negative HER2-Overexpressed Breast Cancer.

BACKGROUNDnDual anti-HER2 therapy is effective for HER2-amplified breast cancer. Weekly paclitaxel, trastuzumab, and full-dose lapatinib (PTL) is not feasible because of grade 3 diarrhea. We conducted a phase II feasibility study of dose-dense (DD; every other week) PTL (ClinicalTrials.gov identifier, NCT01827163).nnnPATIENTS AND METHODSnEligible patients had HER2-positive breast cancer, tumor size ≤ 3 cm, and negative nodes. Treatment included paclitaxel (175 mg/m(2) × 4, every 2 weeks with pegfilgrastim), trastuzumab (4 mg/kg load and then 2 mg/kg weekly), and lapatinib (1000 mg daily). After paclitaxel × 4, trastuzumab (6 mg/kg every 3 weeks) plus lapatinib were continued for 1 year. The primary endpoint was feasibility, defined as (1) > 80% of patients completing PTL without a dose delay or reduction, (2) grade 3 diarrhea rate < 20%, and (3) cardiac event rate < 4%.nnnRESULTSnFrom May 2013 to November 2013, we enrolled 20 of 55 planned patients. The median age was 49 years (range, 34-74 years). One patient had immediate paclitaxel hypersensitivity and was deemed inevaluable. Only 13 of 19 evaluable patients (68%) completed PTL without a dose delay or reduction or unacceptable toxicities. Only 3 of 19 (16%) had grade 3 diarrhea. Rash was frequent, with all grades in 18 of 19 (95%) and grade 3 in 2 of 19 (11%). The study was stopped early because of excess toxicity.nnnCONCLUSIONnThe discontinuation rate during DD PTL was high, owing, in part, to an unexpectedly high incidence of rash. The trial was halted, because the initial discontinuation rate from overall toxicity made it unlikely that full accrual would demonstrate feasibility.

Abstract PD5-3: Phase I trial: PI3Kα inhibitor BYL719 plus aromatase inhibitor (AI) for patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC)

Background: Phosphatidylinositol 3-kinase (PI3K) hyperactivation plays a role in endocrine therapy resistance. Adding an α-selective PI3K inhibitor (BYL719) to hormonal therapy may therefore overcome resistance in HR+ MBC. We report results from a phase I study to evaluate the safety and preliminary efficacy of BYL719 plus an AI in patients (pts) with HR+ MBC. Methods: This 3+3 dose-escalation trial studied daily oral BYL719 added to standard dose letrozole (L, Arm A) or exemestane (E, Arm B), and later examined intermittent dosing (Arm C, L + BYL719 every other week; Arm D, E + BYL719 on 5 of 7 days weekly). Pts with HR+ MBC, any/no PIK3CA mutation, and on L/E were eligible. A cycle (C) was 28 days (d). Endpoints were dose-limiting toxicity (DLT), tolerability (CTCAE 4.0), and efficacy (RECIST v1.1). Paired tumor biopsies were performed for genomic and proteomic correlatives. Serial plasma was collected to quantify cell-free (cf) DNA and mutant allele fraction. Results: 14 pts (median (M) age: 55 (30-69) yrs), 7 each on Arms A and B, received a M of 76d (6-312+) of BYL719 + L or E. All were evaluable for toxicity, 10 for response. PIK3CA status was mutant(MT)/wild-type(WT)/unknown in 8/5/1 pts. M number of prior MBC therapies was 2 (1-12) in Arm A, 6 (2-14) in Arm B. Arms had similar toxicities. On Arm A, BYL719 was given at 300mg daily (DL0) to 3 pts who completed the 28d DLT period. 2 pts had 3 distinct DLTs: maculopapular rash (N=1), hyperglycemia (N=1), abdominal pain (N=1). Dose was de-escalated (DL-1=250mg) with no DLT in 3 enrolled pts. On Arm B, DL0, 1 pt experienced DLT (maculopapular rash) of 3 initially enrolled pts. Arm B expansion at DL0 had 1 additional pt with DLT (rash). Clinically significant, treatment-related toxicities included grade (G)≥4: none; G3: maculopapular rash (N=8, including 1 pt treated at DL-1), hyperglycemia (N=1) and G1/2: fatigue (N=7), nausea (N=7), and hyperglycemia (N=6). Toxicity required 6 dose reductions in 4pts and discontinuation in 2 pts. M duration on study for PIK3CA MT vs. WT was 169.5d vs. 69.5d, respectively. In pts with PIK3CA –MT MBC evaluable for response (n=7), 6 had clinical benefit: 1 PR (pt heavily pre-treated, including prior L, MBC to liver, Arm A, now C10+ after DLT); SD (n=5, included -29.9%, -19%, -12%), and POD (n=1). In pts with PIK3CA -WT MBC evaluable for response (n=3), 2 had SD (no changes ≥+/-5%) and 1 had POD. Serial cfDNA analysis in 4 pts with SD or PR demonstrated a decrease of >90% in the PIK3CA mutant allele fraction on treatment. Due to toxicity seen with continuous BYL719, the study was amended to explore intermittent dosing schedules (Arm C, L; Arm D, E; DL0=250mg), with 5 pts enrolled, 3 of whom have completed the DLT period with no DLTs, and 1 pt with G3 rash. Correlative studies including serial cf DNA collection from these pts is ongoing. Conclusions: Continuously dosed BYL719 with L or E shows promising antitumor activity. Skin toxicity warranted evaluation of alternative schedules. Mutant allele fraction may be an early predictor of response and may serve as a pharmacodynamic marker during intermittent treatment. Safety, efficacy, and correlative data from study Arm C and Arm D will also be presented. Citation Format: Payal D Shah, Mary Ellen Moynahan, Shanu Modi, Betty Ann Caravella, Farrah M Datko, Stephen Zamora, Elizabeth Comen, Theresa Gilewski, Steven M Sugarman, Gabriella D9Andrea, Diana E Lake, Shari B Goldfarb, Sujata Patil, Anne Covey, Michael F Berger, Mario E Lacouture, Larry Norton, Clifford A Hudis, Jose Baselga, Sarat Chandarlapaty, Maura N Dickler. Phase I trial: PI3Kα inhibitor BYL719 plus aromatase inhibitor (AI) for patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD5-3.

Abstract CT330: Phase I study of PI3Kα inhibitor BYL719 + aromatase inhibitor (AI) in patients (pts) with hormone receptor-positive (HR+) metastatic breast cancer (MBC)

Background: Phosphatidylinositol 3-kinase (PI3K) hyperactivation contributes to endocrine therapy resistance. An α-selective PI3K inhibitor (BYL719) added to hormonal therapy may overcome this resistance. We conducted a phase I study to evaluate the safety and determine preliminary efficacy of BYL719 and an AI in pts with HR+ MBC. Methods: This 3+3 dose-escalation trial added oral BYL719 to letrozole (L) or exemestane (E) at standard doses using daily (Arm A: L; Arm B: E) and then intermittent dosing (Arm C: L + BYL719 every other week; Arm D: E + BYL719 on 5 of 7 days weekly). Pts with HR+ MBC, any or no PIK3CA mutation, and already on L/E were eligible. Endpoints were dose-limiting toxicity (DLT), tolerability (CTCAE 4.0), and efficacy. Paired tumor biopsies and serial plasma collection facilitated genomic, proteomic, and cell-free (cfDNA) correlatives. Results: 32 patients (Arm A/B: n = 7/7; Arm C/D: n = 9/9) received a mean of 99 days (range: 6-473d) of BYL719 + L or E. All were evaluable for toxicity; 25 (Arm A/B: 5/5; Arm C/D: 7/8) were evaluable for response. Median (M) age was 58.5 (30-83). M number of prior MBC therapies was 3 (1-12). PIK3CA status was mutant(MT)/wild-type(WT)/unknown in 8/5/1 pts on Arms A+B and 17/1/0 on Arms C+D. During dose escalation on Arms A+B, 14 pts received BYL719 doses up to 300mg/d, where 4 pts had 5 distinct DLTs: maculopapular rash (N = 3), hyperglycemia (N = 1), abdominal pain (N = 1). 8 week (w) best response on continuous dosing arms (n = 10 evaluable pts) was 1 PR (pt heavily pre-treated, including prior L, MBC to liver, Arm A, completed 10C); 7 SD (included -29.9%, -19%, -12%), and 2 POD. Due to toxicity, enrollment to these arms was halted prior to MTD determination. The protocol was amended to include 2 intermittent dosing arms. 3 DLTs were seen: Arm C, grade (G)3 rash, G1 fever and hypotension with >7d therapy hold; Arm D, G3 rash. Toxicities (Arms C+D, all cohorts, n = 18) included G≥4: hyperglycemia (n = 1, while pt on corticosteroids); G3: rash (n = 4); G1/2: mucositis (n = 9), hyperglycemia (n = 8), and anorexia (n = 5). MTD determinations are pending with evaluation of 350mg BYL719 5d on, 2d off ongoing on Arm D. On Arm C, of 7 evaluable pts, best response was SD in 3 pts (28w, 12w, 8+w in 1 pt each) and POD in 4 pts. On Arm D, of 8 evaluable pts, best response is SD in 6 pts (28+w, 16+w in 1 pt each; 20w, 8+w in 2 pts each), and POD in 2 pts. Using serial cfDNA analysis, PIK3CA mutant allele fraction declined with SD and PR and increased in pts with POD. Correlative studies including genomics and proteomics are ongoing. Conclusions: BYL719 with L or E is an active combination. Skin toxicity warranted evaluation of alternate schedules. A 5d on, 2d off schedule of BYL719 + exemestane appears tolerable and may allow for higher doses than daily administration, with MTD determination pending. Further safety, efficacy, and correlative data will be presented. Citation Format: Payal D. Shah, Mary E. Moynahan, Shanu Modi, Nicola Hamilton, Betty Ann Caravella, Stephen Zamora, Chau Dang, Theresa Gilewski, Tiffany Traina, Elizabeth Comen, Steven M. Sugarman, Gabriella D9Andrea, Diana Lake, Shari Goldfarb, Sujata Patil, Anne Covey, Michael Berger, Mario Lacouture, Larry Norton, Clifford A. Hudis, Jose Baselga, Sarat Chandarlapaty, Maura Dickler. Phase I study of PI3Kα inhibitor BYL719 + aromatase inhibitor (AI) in patients (pts) with hormone receptor-positive (HR+) metastatic breast cancer (MBC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT330. doi:10.1158/1538-7445.AM2015-CT330