Poster Discussion Session: Breast Cancer—Local/Regional/Adjuvant
vailable Starting on Friday, June 4, 2021; 9:00 EDT
507 Usefulness of assessment of circulating tumor DNA(ctDNA) of cerebrospinal fluid(CSF) samples for early detection of brain metastasis (BrM) in patients with triple-negative breast cancer (TNBC). L Raimondi, G Naso, R Lazzeroni, et al
- This study evaluated whether CSF-derived circulating tumor DNA (ctDNA) predicted brain metastases in 323 women with newly diagnosed triple-negative breast cancer (TNBC). Following treatment with neoadjuvant therapy and surgery, 126 patients (39%) had detectable ctDNA. Brain metastases developed in 98.4% of patients who had detectable ctDNA compared with 1% of patients without detectable ctDNA (P <.001). Compared with patients with detectable ctDNA, those with undetectable cdDNA had significantly better PFS (HR, 0.3) and OS (HR, 0.2). In multivariable analysis, detectable ctDNA was the strongest predictor of the combined outcome of brain metastases and death at 24 months of follow-up (HR, 3.62).
- CSF-derived ctDNA following neoadjuvant therapy and surgery is a reliable biomarker of brain metastases and mortality among women diagnosed with TNBC.
517 Abemaciclib combined with adjuvant endocrine therapy in patients with high risk early breast cancer who received neoadjuvant chemotherapy (NAC). M Martin, R Hegg, S-B Kim, et al
- The phase III monarchE study compared abemaciclib combined with adjuvant endocrine therapy (ET) with ET alone in patients with HR+/HER2– high-risk early breast cancer. The current analysis included 2056 patients with invasive disease previously treated with neoadjuvant chemotherapy. In multivariable analysis, compared with patients who had ET alone, patients who received abemaciclib + ET had significantly better invasive disease–free survival (HR, 0.61; 2-year survival, 87.2% vs 80.6%), and better distant relapse–free survival (HR, 0.61; 2-year survival, 89.5% vs 82.8%). Safety outcomes were similar in both patient groups.
- Abemaciclib + ET demonstrated a significant survival benefit in women with invasive, HR+/HER2– high-risk early breast cancer previously treated with neoadjuvant chemotherapy.
Poster Session: Breast Cancer—Local/Regional/Adjuvant
Available Starting on Friday, June 4, 2021; 9:00 EDT
526 Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: A subgroup analysis of the DESTINY-Breast01 trial. GHM Jerusalem, YH Park, T Yamashita, et al
- Findings of the DESTINY-Breast01 study demonstrated the significant survival benefit associated with the antibody–conjugate drug Trastuzumab deruxtecan (T-DXd) for unresectable or metastatic HER2+ breast cancer previously treated with trastuzumab emtansine. This subanalysis of DESTINY-Breast01 compared patients with and without a history of brain metastases, finding comparable objective response rates (ORR), median progression-free survival (mPFS), and median duration of response (mDoR) in both patient groups. Following treatment with T-DXd, patients with history of brain metastases had an ORR of 58%, an mPFS of 18.1 months, and an mDoR of 16.9 months.
- T-DXd showed a strong clinical benefit in patients with unresectable or metastatic HER2+ breast cancer, regardless of brain metastases.
574 Pyrotinib as neoadjuvant therapy for HER2+ breast cancer: A multicenter, randomized, controlled, phase II trial. X Ding, W Mo, X Xie, et al
- In this phase II trial, patients with cT2-3N0-3M0 stage, HER2+ breast cancer were randomly assigned to receive six cycles of trastuzumab + docetaxel + carboplatin (TCbH; n = 33) or TCbH + pyrotinib (n = 34). Compared with patients in the TCbH arm, those in the TCbH + pyrotinib arm had a significantly better pathological complete response rate (36.7% vs 71.4%) and a numerically better objective response rate (83.3% vs 100%). Diarrhea of grade 3 was the most common adverse event, occurring in 28.6% and 10% of patients in the TCbH + pyrotinib arm and TCbH arm, respectively.
- In the setting of neoadjuvant therapy for HER2+ breast cancer, the addition of pyrotinib to TCbH improved treatment responses and had a manageable safety profile.
Poster Session: Breast Cancer—Metastatic
Available Starting on Friday, June 4, 2021; 9:00 EDT
1039 Safety of trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive locally advanced or metastatic breast cancer (mBC): Final results from KAMILLA Cohorts 1 (global) and 2 (Asia). R Wuerstlein, P Ellis, F Montemurro, et al
- These authors compared safety outcomes in two patient cohorts from KAMILLA, a trial assessing the safety of the targeted therapy T-DM1 in patients with previously treated, locally advanced or metastatic HER2+ breast cancer. Length of exposure to T-DM1 was similar in the Asian cohort (n = 362) and the global cohort (n = 2002; median, 5.6 vs 5.0 months). Prespecified adverse events (hepatic events, allergic reactions, thrombocytopenia [TCP]) of grade ≥3 were more common in the Asian compared with the global cohort, particularly TCP. Treatment-related adverse events were also significantly more common in the Asian (48.6%) compared with the global cohort (18.4%). The cohorts had similar rates of progression-free survival and overall survival.
- T-DM1 was associated with higher rates of adverse events of grade ≥3 among Asian compared with global patients, a finding in agreement with that of previous studies. Nevertheless, a survival benefit with T-DM1 for previously treated metastatic breast cancer was seen in all patients.
1043 Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB). G Curigliano, V Mueller, VF Borges, et al
- The report of an updated analysis of HER2CLIMB trial data will present overall survival, progression-free survival, and safety outcomes in the overall study population and stratified by brain metastases, ECOG performance status, and geographic region.
1055 Overall survival in patients with breast cancer treated with a CDK 4/6 inhibitor plus fulvestrant: A U.S. Food and Drug Administration pooled analysis. JJ Gao, J Cheng, TM Prowell, et al
- The study authors conducted a pooled, exploratory analysis of data from trials evaluating treatment with CDK inhibitors plus fulvestrant for locally advanced or metastatic, HR+/HER2– breast cancer. The addition of a CDK inhibitor to fulvestrant improved overall survival in most patient subgroups, which were defined by demographic and clinicopathologic factors. However, among younger patients (<40 years old; n = 89), the overall survival was better among treated with fulvestrant alone compared with those treated with fulvestrant plus a CDK inhibitor.
- In most patient subgroups, the addition of a CDK inhibitor to fulvestrant enhanced survival compared with fulvestrant alone.
1080 Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC). LA Carey, D Loirat, K Punie, et al
- The ASCENT trial evaluated the antibody–drug conjugate sacituzumab govitecan in the setting of metastatic triple-negative breast cancer (mTNBC). This subanalysis evaluated outcomes among patients who had disease recurrence within 12 months of neoadjuvant chemotherapy and one second-line therapy; no patients had brain metastases. Compared with patients who received a second-line treatment of physician’s choice (n = 32), those who received second-line sacituzumab govitecan (n = 33) had significantly longer progression-free survival (median, 5.7 vs 1.5 months) and overall survival (median, 10.9 vs 4.9 months) and objective response rate (30% vs 3%).
- Sacituzumab govitecan conferred a significant survival advantage over physician’s choice in the context of second-line treatment in patients with mTNBC but without brain metastases.
Oral Abstract Session: Breast Cancer—Metastatic
Saturday, June 5, 2021; 1:30 PM–4:30 PM EDT
1000 Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3. M Cristofanilli, HS Rugo, S-A Im, et al
- The phase III PALOMA-3 trial evaluated the addition of palbociclib to fulvestrant (PAL + FUL) for treatment of HR+/HER2– advanced breast cancer with progression following endocrine therapy, finding a significant survival benefit for PAL + FUL compared with FUL alone. The current analysis demonstrates a continuation of this trend. After a median follow-up of 73.3 months, PAL + FUL was associated with better OS compared with FUL alone (HR, 0.81), as well as better 5-year OS rates (23.3% vs 16.8%). This trend was observed in most patient subgroups, except those in which patients were endocrine-resistant or had previous chemotherapy for advanced breast cancer.
- Study findings support the continued clinical benefit of PAL + FUL over the longer term for treatment of HR+/HER2– advanced breast cancer.
1001 Updated overall survival (OS) results from the phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2- advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). DJ Slamon, P Neven, SKL Chi
- Findings from the MONALEESA-3 trial demonstrated a survival benefit with ribociclib plus fulvestrant (RIB + FUL) compared with FUL alone for treatment of HR+/HER2– advanced breast cancer in postmenopausal women. This trend continued over longer-term follow-up (median, 56.3 months). Compared with patients who received FUL alone, those who received RIB + FUL had longer overall survival (median, 53.7 vs 41.5 months); this finding was observed regardless of whether patients were receiving first- or second-line therapy. The clinical benefit of RIB + FUL was also observed for progression-free survival and chemotherapy-free survival.
- An ongoing clinical benefit of adding to RIB to FUL for treatment of HR+/HER2– advanced breast cancer continued after almost 5 years of follow-up.
1002 Dalpiciclib versus placebo plus fulvestrant in HR+/HER2- advanced breast cancer that relapsed or progressed on previous endocrine therapy (DAWNA-1): A multicenter, randomized, phase 3 study. B Xu, Q Zhang, P Zhang, et al
- In the phase III DAWNA-1 study, 361 patients with HR+/HER2− locally advanced or metastatic breast cancer were randomized 2:1 to receive fulvestrant plus either dalpiciclib, a novel CDK4/6 inhibitor, or placebo. Progression-free survival was significantly improved in the group receiving dalpiciclib (median 15.7 months vs 7.2 months; HR, 0.42; 95% CI, 0.31–0.58; P < .0001).
- Adding dalpiciclib to fulvestrant improved progression-free survival in patients with HR+/HER2− advanced/metastatic breast cancer.
Oral Abstract Session: Breast Cancer—Local/Regional/Adjuvant
Sunday, June 6, 2021; 8:00 AM–11:00 AM EDT
500 Outcome of patients with an ultralow risk 70-gene signature in the MINDACT trial. JL Cardozo, C Drukker, M Schmidt, et al
- Study authors used data from the phase III MINDACT trial to assess survival among 1000 patients stratified on the 70-gene MammaPrint assay (MP) as ultra–low risk for distant recurrence of breast cancer. The overall 8-year distant metastasis–free interval (DMFI) in ultra–low risk patients was 97%; DMFI was similar after adjustment for tumor and treatment characteristics.
- Patients stratified as ultra–low risk for distant recurrence of breast cancer on MP had an 8-year survival rate of over 95%, regardless of treatment or tumor type.
501 Breast Cancer Index (BCI) and prediction of benefit from extended aromatase inhibitor (AI) therapy (tx) in HR+ breast cancer: NRG oncology/NSABP B-42. EP Mamounas, H Bandos, P Rastogi, et al
- In the phase III NSABP B-42 trial, the authors evaluated extended letrozole treatment (ELT) among 2179 patients with HR+ breast cancer who had completed 5 years of endocrine therapy. Overall, ELT improved 10-year recurrence-free survival by 1.6%. Breast cancer–free survival, disease-free survival, and distant recurrence over the shorter-term (<4 years) did not vary significantly by the Breast Cancer Index (BCI) HOXB13/IL17BR ratio (BCI-H/I). However, after 4 years of follow-up, ELT significantly reduced distant recurrence among patients with a high BCI-H/I (HR, 0.29; P = .003) but not among patients with a low BCI-H/I (HR, 0.68; P = .28).
- The BCI-H/I did not predict the effect of ELT on 10-year recurrence-free survival among patients with HR+ breast cancer. Beyond 4 years of follow-up, ELT reduced distant recurrence but only among patients with a high BCI-H/I.
502 Utility of the 70-gene MammaPrint assay for prediction of benefit from extended letrozole therapy (ELT) in the NRG Oncology/NSABP B-42 trial. P Rastogi, H Bandos, PC Lucas, et al
- In the phase III NSABP B-42 trial, the study investigators evaluated whether the 70-gene MammaPrint assay (MP) predicted the benefit of extended letrozole treatment (ELT) among patients with HR+ breast cancer who had completed 5 years of endocrine therapy. ELT had a significant benefit in terms of distant recurrence among patients stratified by MP as low risk (HR, 0.43; P = .002) but not among patients stratified as high-risk (HR, 0.65; P = .19). Similar trends were observed for disease-free survival and breast cancer–free survival. Among patients stratified by MP as low risk, those with ultra-low risk had the greatest benefit from ELT for all outcomes.
- In the setting of HR+ breast cancer, a significant benefit of ELT was observed among patients stratified as low risk on MP but not among those stratified as high risk. The benefit was greatest among patients with ultra-low risk.
503 De-escalated neoadjuvant pertuzumab+trastuzumab with or without paclitaxel weekly in HR-/HER2+ early breast cancer: ADAPT-HR-/HER2+ biomarker and survival results. N Harbeck, O Gluz, M Christgen, et al
- The authors present first survival data for the ADAPT HR−/HER2+ study, in which 134 patients with HR-negative (ER and PR <1%) and HER2-positive tumors were randomly assigned to receive four cycles of neoadjuvant pertuzumab (P) plus trastuzumab (T) with or without paclitaxel (PAC), with the aim of comparing partial complete response in the two arms.
- Because of the partial complete response superiority observed for the P+T+PAC group, the trial was stopped early. Of the 69 patients with a partial complete response, 39 (56.5%) did not receive further chemotherapy (9 in the P+T group vs 30 in the P+T+PAC group). A single distant relapse (1.4%) occurred.
505 Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. JK Litton, JT Beck, JM Jones, et al
- This phase II nonrandomized single-arm study evaluated the safety and efficacy of PARP inhibitor talazoparib in patients with germline BRCA1/2–mutated HER2-negative locally advanced or metastatic breast cancer. The primary endpoint was pathologic complete response after 24 weeks of neoadjuvant talazoparib (1 mg daily) monotherapy followed by surgery. All 61 patients had triple-negative disease; 48 patients comprised the evaluable population. Approximately 98% of the patients experienced treatment-emergent adverse events, primarily fatigue, nausea, and alopecia.
- Results showed talazoparib to be well-tolerated overall and active in the neoadjuvant setting, with pathologic complete response rates similar to rates noted with combined anthracycline and taxane regimens.
506 Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC). S Loibl, A Schneeweiss, JB Huober, et al
- The GeparNeuvo study was designed to examine the benefits of adding durvalumab to preoperative chemotherapy in early-stage A total of 174 patients with cT1b-cT4a-d tumors and centrally confirmed TNBC were randomized to receive either durvalumab or placebo monotherapy for 2 weeks, followed by the addition of nab-paclitaxel weekly for 12 weeks and then durvalumab/placebo plus epirubicin/cyclophosphamide every 2 weeks for four cycles.
- The 3-year invasive disease–free survival with durvalumab was 84.9% versus 76.9% with placebo, and 3-year overall survival with durvalumab was 95.1% versus 83.1% with placebo. Durvalumab appears to improve long-term outcomes in patients with TNBC.
605 A randomized phase III post-operative trial of platinum-based chemotherapy (P) versus capecitabine (C) in patients (pts) with residual triple-negative breast cancer (TNBC) following neoadjuvant chemotherapy (NAC): ECOG-ACRIN EA1131. IA Mayer, F Zhao, CL Arteaga, et al
- The authors sought to determine whether the use of platinum chemotherapy is superior to use of capecitabine for improving invasive disease–free survival (IDFS) in patients with basal-subtype early-stage TNBC and residual disease after preoperative chemotherapy. A total of 401 patients with clinical stage II/III TNBC (310 with basal subtype) and ≥1 cm residual invasive disease post neoadjuvant chemotherapy were randomized 1:1 to receive either platinum-based chemotherapy (carboplatin or cisplatin) or capecitabine.
- The 3-year IDFS was 40% for the platinum group and 44% for the capecitabine group. The trial was stopped upon recommendation at the fifth interim analysis because of the unlikelihood that it would demonstrate noninferiority or superiority of the platinum regimen. In patients with TNBC, in particular those with the basal subtype, and ≥1 cm residual disease after neoadjuvant chemotherapy, adjuvant platinum chemotherapy did not improve outcomes.
Sunday, June 6, 2021; 1:00 PM–4:00 PM EDT
LBA1 OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer. A Tutt, JE Garber, B Kaufman, et al
- This plenary session presentation demonstrates the benefits of adjuvant olaparib in early-stage BRCA-mutant breast cancer.