Dalpiciclib Combined With Pyrotinib and Letrozole in Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer (LORDSHIPS): A Phase Ib Study

Zhang, Jian; Meng, Yanchun; Wang, Biyun; Wang, Leiping; Cao, Jun; Tao, Zhonghua; Li, Ting; Yao, Wenqing; Hu, Xichun

doi:10.3389/fonc.2022.775081

Cited by 13 publications

(9 citation statements)

References 34 publications

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“…14 Department of Anesthesiology, the First Affiliated Hospital of China Medical University, Shenyang, China. 15 Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. 16 Instituto Brasileiro de Controle do Câncer Oncologia (IBCC Oncologia), São Paulo, Brazil.…”

Section: Reporting Summarymentioning

confidence: 99%

“…Preclinical studies have suggested that dalpiciclib can overcome the resistance to HER2-targeted blockade and endocrine therapy in ERpositive, HER2-positive breast cancer cells 14 . The phase 1b LORDSHIPS study has suggested a potentially synergistic anti-tumor effect with pyrotinib, letrozole, and dalpiciclib in front-line patients with HRpositive, HER2-positive metastatic breast cancer 15 .…”

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confidence: 99%

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A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer

Niu

Qiu

et al. 2022

Nat Commun

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Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II–III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)−0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3–41.3). RCB-0/I is 55.7% (95% CI, 44.7–66.1). ORR is 87.4%, (95% CI, 78.1–93.2) and bpCR is 35.4% (95% CI, 25.8–46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.

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Section: Reporting Summarymentioning

confidence: 99%

mentioning

confidence: 99%

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer

Niu

Qiu

et al. 2022

Nat Commun

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“…The toxicity of this treatment was tolerable. [11] In this case, we chose trastuzumab, leuprolide, letrozole, and piperacillin as first-line treatment regimens and achieved good therapeutic effects. The reasons for successful treatment in this case as follows: Expression of HR (ER 80% +, PR 60% +) and the biological characteristics of the patient's tumor were better than those with low HR expression, closer to HER2-negative and HR-positive breast cancers.…”

Section: Discussionmentioning

confidence: 99%

Trastuzumab, leuprorelin, letrozole, and palbociclib as first-line therapy in HER2-positive and hormone receptor-positive metastatic breast cancer: A case report

Sun¹,

Liang-zhen²,

Chen³

2023

Medicine

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Rationale: Cyclin-dependent kinase 4/6 inhibitors are promising candidates for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, current international guidelines recommend endocrine therapy alone or with HER2-targeted therapy to treat HER2-positive and hormone receptor (HR)-positive metastatic breast cancer in patients who cannot tolerate first-line chemotherapy. Moreover, data on the effectiveness and safety of cyclin-dependent kinase 4/6 inhibitors combined with trastuzumab and endocrine therapy as a first-line treatment for HER2-positive and HR-positive metastatic breast cancer are limited. Patient concerns: A 50-year-old premenopausal woman was with epigastric pain for more than 20 days. Ten years ago, she was diagnosed with left breast cancer and underwent surgical treatment, chemotherapy, and endocrine therapy. Diagnoses: After relevant examination, the patient was diagnosed with liver, lung, and left cervical lymph node metastatic HER2-positive and HR-positive carcinoma from the left breast after systemic therapy. Interventions: The laboratory investigations showed that the patient’s liver function was seriously damaged due to the liver metastases, and the patient was assessed as unable to tolerate chemotherapy. She was treated with trastuzumab, leuprorelin, letrozole, and piperacillin combined with percutaneous transhepatic cholangic drainage. Outcomes: The patient’s symptoms were relieved, her liver function returned to normal, and the tumor showed partial response. Neutropenia (Grade 3) and thrombocytopenia (Grade 2) occurred during treatment but improved after symptomatic treatment. To date, the progression-free survival of the patient is over 14 months. Lessons: We believe that trastuzumab, leuprorelin, letrozole, and palbociclib is a feasible and effective treatment for HER2-positive and HR-positive metastatic breast cancer in premenopausal patients who cannot tolerate first-line chemotherapy.

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“…Therefore, targeted combination endocrine therapy has the potential to replace traditional chemotherapy combined with anti HER2 targeted therapy in the population of TPBC advanced patients who have failed anti HER2 treatment. Zhang et al [31] conducted a Phase Ib clinical study(LORDSHIPS) on the first/second line treatment of advanced TPBC patients with a combination regimen of dalpiciclib, pyrotinib, and letrozole. The study included 15 patients with advanced TPBC, with a median follow-up time of 11.4 months.…”

Section: Discussionmentioning

confidence: 99%

Whether AI+CDK4/6i+HP is suitable treatment for three positive metastatic breast cancer patient with renal insufficiency caused by type 2 diabetes

Gang,

Li,

et al. 2023

Preprint

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Background: Hormone-receptor positive (HR+)，ERBB2 gene mutation(HER2+)breast cancer is a very common type of breast cancer, but it is relatively rare for metastatic breast cancer (MBC) who are newly treated and have renal insufficiency. In previous studies, no long-term survival reports have been found for such patients. In order to clarify the above issues, we have innovatively developed a plan that focuses on molecular targeted therapy and endocrine therapy.We reported the results of a breast cancer patient with HR+and HER2+concurrent renal insufficiency. Although the patient did not have the opportunity to receive surgical treatment and chemotherapy, the results showed that the aromatase inhibitors(AI)+Cyclin D-cyclin-dependent kinase 4/6 inhibitor(CDK4/6i)+trastuzumab & pertuzumab(HP) treatment was also an effective and feasible approach. Patient and methods: The patient with HR+ HER2-positive MBC with activating HER2 mutation(s) received AI+CDK4/6i+HP(oral letrozole 2.5 mg/day,oral abemaciclib 150mg twice/day with mandatory loperamide prophylaxis for the first 2 cycles and as needed thereafter , and intravenous trastuzumab 8mg/kg initially then 6 mg/kg every 3 weeks plus pertuzumab 840mg initially then 420mg every 3 weeks ) therapy. Efficacy endpoints included progression-free survival (PFS) (RECIST v1.1). Secondary endpoints are treatment time, exploratory targets are tumor markers, and safety targets are changes of renal function. Plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. Results: The duration of response time lasted for approximately 60 weeks. The treatment time was 81weeks.The PFS was 17.6 months. Responses were observed in patient within 6 weeks. Longitudinal ctDNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA.Throughout the entire treatment cycle, the patient's renal function remained stable, with no significant fluctuations in creatinine, creatinine clearance rate, serum urea, and serum potassium. Conclusions: AI+CDK4/6i+HP is a safe and effective treatment for patients with three positive metastatic breast cancer patients with renal insufficiency caused by type 2 diabetes. Throughout the entire treatment process, the patient's renal function remains stable.Further investigation is needed.

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Dalpiciclib Combined With Pyrotinib and Letrozole in Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer (LORDSHIPS): A Phase Ib Study

Cited by 13 publications

References 34 publications

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer

Trastuzumab, leuprorelin, letrozole, and palbociclib as first-line therapy in HER2-positive and hormone receptor-positive metastatic breast cancer: A case report

Whether AI+CDK4/6i+HP is suitable treatment for three positive metastatic breast cancer patient with renal insufficiency caused by type 2 diabetes

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