A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS604-TPS604
Author(s):  
Sherene Loi ◽  
Heather L. McArthur ◽  
Nadia Harbeck ◽  
Lajos Pusztai ◽  
Suzette Delaloge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Adjuvant Endocrine Therapy ◽  
Phase Iii ◽  
Free Survival ◽  
Her2 Breast Cancer ◽  
Programmed Death ◽  
Er Expression

TPS604 Background: Patients (pts) diagnosed with primary estrogen receptor-positive (ER+), human epidermal growth factor 2-negative (HER2−) breast cancer (BC) of high grade and/or low ER expression are at increased risk of relapse, despite current standard of care (SoC). Promising data assessing programmed death-1 (PD-1) inhibition coupled with neoadjuvant chemotherapy for pts with high-risk ER+, HER2− BC noted improved pathologic complete response (pCR), which is identified as a valid surrogate endpoint for long-term clinical outcomes. Methods: CheckMate 7FL (NCT04109066) is a randomized, double-blind, placebo-controlled, multicenter, global phase 3 study evaluating nivolumab (NIVO) vs placebo (PBO) in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy (ET) in pts with high-risk, ER+, HER2− primary BC. Eligible pts are male or female, aged ≥18 years with newly diagnosed grade 2 with ER expression of 1–9%, or grade 3, T1c-2, cN1-2 (tumor size ≥2 cm) or T3-T4, cN0-cN2 ER+, HER2− BC. Pts eligible for neoadjuvant chemotherapy and surgery, with adequate organ function, ECOG PS of 0 or 1, and tissue available for biomarker assessments will be enrolled. Approximately 1200 pts will be randomized 1:1 to NIVO or PBO, stratified by programmed death ligand 1 (PD-L1) expression, tumor grade (2 or 3), axillary nodal status (+ or −), and anthracycline + cyclophosphamide schedule (Q3W or Q2W). In the neoadjuvant phase, pts will receive NIVO 360 mg Q3W or PBO + paclitaxel 80 mg/m2 QW for four 3-week cycles, followed by NIVO 360 mg Q3W (or 240 mg Q2W) or matching PBO in combination with either doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 Q3W or Q2W for 4 cycles. Pts will undergo surgery after completion of the neoadjuvant phase. Following surgery, pts will enter the adjuvant phase and receive NIVO 480 mg Q4W or PBO for 7 cycles + investigator’s choice of ET per local SoC. Primary endpoints are pCR (ypT0/is, ypN0) and event-free survival. Secondary endpoints include overall survival, disease-free survival, distant-metastasis-free survival, safety, pCR (ypT0 ypN0 and ypT0/is) rates, overall response rates, residual cancer burden, and quality of life. Interim analyses are planned. The study is currently enrolling. Clinical trial information: NCT04109066 .

Palbociclib combined with endocrine treatment in breast cancer patients with high relapse risk after neoadjuvant chemotherapy: Subgroup analyses of premenopausal patients in PENELOPE-B.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 518-518
Author(s):  
Frederik Marmé ◽  
Miguel Martin ◽  
Michael Untch ◽  
Herve R. Bonnefoi ◽  
Sung-Bae Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Endocrine Treatment ◽  
Hematologic Toxicity

518 Background: PENELOPE-B assessed efficacy of the CDK4/6 inhibitor 1-year palbociclib versus placebo added to endocrine therapy (ET) as post-neoadjuvant treatment in a high-risk breast cancer population. Palbociclib did not improve invasive disease-free survival (iDFS) compared to placebo (3-year iDFS 81.3% vs 77.7%) (Loibl et al. J Clin Oncol 2021). Here we report results from the subpopulation of premenopausal women. Methods: Patients with hormone receptor positive, HER2-negative breast cancer without pathological complete response after taxane‐containing neoadjuvant chemotherapy and at high risk of relapse (CPS‐EG score ≥3 or 2 and ypN+) were randomized (1:1) to receive 13 cycles of palbociclib 125mg daily or placebo on days 1-21 in a 28d cycle in addition to standard endocrine treatment including tamoxifen (TAM) +/- gonadotropin-releasing hormone analogue (GnRH) and aromatase inhibitor (AI) +/- GnRH. Randomization was stratified by nodal status at surgery, age ( < 50 vs ≥50 years), Ki-67, region, and CPS-EG score. Results: 616/1250 patients were premenopausal at the time of enrollment, 185 of these patients (30.0%) were younger than 40 years of age. 95.2% had ypN+ after surgery; 42.8% had ypT2 and 46.8% a CPS-EG score of 3. 23.1% of the premenopausal women had a Ki67 of > 15% in residual disease. 66.1% started with TAM alone; 19.3% with TAM and ovarian function suppression (OFS); and 13.6% received an AI+OFS. There was no difference in iDFS between palbociclib and placebo in the premenopausal women HR 0.948 (0.693-1.30). The 3-year iDFS was 80.6% and 78.3%, respectively. Palbociclib vs placebo in subgroups by endocrine treatment: TAM alone HR 1.05 (0.715-1.53) p = 0.817; TAM+GnRH HR 0.52 (0.267-1.02) p = 0.057 and AI+GnRH HR 1.58 (0.548-4.56) p = 0.397; pinteraction0.124. Hematologic toxicity was significantly more common with palbociclib. Non-hematological toxicity any grade palbociclib vs placebo were: fatigue 67.4% vs 51.3%; hot flushes 52.2% vs 54.8%; bone pain 15.6% vs 16.6%; and vaginal dryness 11.0% vs 11.5%. When receiving palbociclib fewer patients in the AI+GnRH group vs the TAM +/- GnRH cohort experienced anemia (54.1% vs 80.5%) and thrombocytopenia (37.8% vs 65.1%). Fatigue (75.7% vs 66.3%) and nausea (40.5% vs 24.9%) were more common with AI+GnRH than TAM +/-GnRH when palbociclib was added. Thromboembolic events were low with overall 9 events (4 vs 5; AI+GnRH 2.4% vs 1.3% TAM+/-GnRH). Conclusions: The addition of palbociclib to endocrine therapy did not improve iDFS in premenopausal women. These are the first safety results from a phase III study for the combination tamoxifen +/-GnRH and palbociclib. The addition of palbociclib to tamoxifen +/-GnRH in premenopausal women did not increase side effects compared to AI+GnRH and seems to be an alternative to AI+GnRH. Clinical trial information: NCT01864746.

Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)

2021 ◽  
Author(s):  
Michael Gnant ◽  
Amylou C. Dueck ◽  
Sophie Frantal ◽  
Miguel Martin ◽  
Hal J. Burstein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Hormone Receptor ◽  
Adjuvant Endocrine Therapy ◽  
Phase Iii ◽  
End Points ◽  
Free Survival ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

PURPOSE Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor–positive breast cancer has not been confirmed. PATIENTS AND METHODS In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer–free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival. RESULTS Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial. CONCLUSION At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor–positive breast cancer.

scholarly journals Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE)

2020 ◽  
Vol 38 (34) ◽  
pp. 3987-3998 ◽  
Author(s):  
Stephen R. D. Johnston ◽  
Nadia Harbeck ◽  
Roberto Hegg ◽  
Masakazu Toi ◽  
Miguel Martin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Distant Recurrence ◽  
Early Recurrence ◽  
Phase Iii ◽  
Free Survival ◽  
Node Positive ◽  
Pathologic Features

PURPOSE Many patients with HR+, HER2− early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients. Abemaciclib is an oral, continuously dosed, CDK4/6 inhibitor approved for HR+, HER2− advanced breast cancer (ABC). Efficacy and safety of abemaciclib in ABC supported evaluation in the adjuvant setting. METHODS This open-label, phase III study included patients with HR+, HER2−, high-risk EBC, who had surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with four or more positive nodes, or one to three nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%, were eligible and randomly assigned (1:1) to standard-of-care adjuvant endocrine therapy (ET) with or without abemaciclib (150 mg twice daily for 2 years). The primary end point was invasive disease-free survival (IDFS), and secondary end points included distant relapse–free survival, overall survival, and safety. RESULTS At a preplanned efficacy interim analysis, among 5,637 randomly assigned patients, 323 IDFS events were observed in the intent-to-treat population. Abemaciclib plus ET demonstrated superior IDFS versus ET alone ( P = .01; hazard ratio, 0.75; 95% CI, 0.60 to 0.93), with 2-year IDFS rates of 92.2% versus 88.7%, respectively. Safety data were consistent with the known safety profile of abemaciclib. CONCLUSION Abemaciclib when combined with ET is the first CDK4/6 inhibitor to demonstrate a significant improvement in IDFS in patients with HR+, HER2− node-positive EBC at high risk of early recurrence.

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