Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up

Rugo, Hope S.; Finn, Richard S.; Dièras, Véronique; Ettl, Johannes; Lipatov, Oleg; Joy, Anil A.; Harbeck, Nadia; Castrellon, Aurelio; Iyer, Shrividya; Lu, Dongrui R.; Mori, Alessia; Gauthier, Eric; Bartlett, Cynthia Huang; Gelmon, Karen A.; Slamon, Dennis J.

doi:10.1007/s10549-018-05125-4

Cited by 302 publications

(342 citation statements)

References 17 publications

(20 reference statements)

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“…Endocrine therapy and CDK 4/6 inhibitor combinations have substantially prolonged progression-free survival making them a standard of care for advanced luminal breast cancer. [2][3][4][5][6][7][8] Increased transaminases have been described as adverse events in previous phase 3 trials (Table 1).…”

Section: Discussionmentioning

confidence: 98%

“…Here, for the first time, we report the case of a rechallenge of a CDK 4/6 inhibitor after serious liver toxicity. Endocrine therapy and CDK 4/6 inhibitor combinations have substantially prolonged progression‐free survival making them a standard of care for advanced luminal breast cancer . Increased transaminases have been described as adverse events in previous phase 3 trials (Table ).…”

Section: Discussionmentioning

confidence: 99%

“…Increased transaminases have been described as adverse events in previous phase 3 trials (Table ). Elevated ALAT (all grades) occurred in 6%‐15% of patients, including Grade 3 in 2%‐7.5% of patients . A pooled analysis of ribociclib studies revealed 7% Grade 3 ALAT increases, leading to permanent discontinuation of the treatment for the majority of patients .…”

Section: Discussionmentioning

confidence: 99%

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CDK 4/6 inhibitor successful rechallenge after limiting hepatic toxicity

Meynard

Grellety

2019

Breast J

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A 59‐year‐old woman presented with a bone‐only metastatic luminal breast cancer. She received first‐line treatment with aromatase inhibitors associated with a cyclin‐dependent kinase (CDK) 4/6 inhibitor, ribociclib. She developed Grade 3 elevated transaminases leading us to interrupt ribociclib permanently. Specific toxicity of the CDK 4/6 inhibitor ribociclib was retained. Once transaminase levels normalized, the patient initiated another CDK4/6 inhibitor, palbociclib, using an escalating dose without reappearance of hepatic injury. This case suggests the possibility of rechallenge after hepatic toxicity with a different CDK 4/6 inhibitor using dose escalation and careful monitoring.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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CDK 4/6 inhibitor successful rechallenge after limiting hepatic toxicity

Meynard

Grellety

2019

Breast J

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“…In the PALOMA‐2 and PALOMA‐3 trials, palbociclib plus ET prolonged PFS in the North American and overall populations (median PFS in PALOMA‐2: 25.4 and 27.6 months, respectively; PALOMA‐3: 9.9 and 11.2 months, respectively) and delayed treatment with cytotoxic chemotherapy. Updated data for North American patients from the PALOMA‐3 trial also indicated that OS was longer with palbociclib vs placebo (32.0 vs 24.7 months, HR, 0.75 [95% CI, 0.53–1.04]), P = .0869]), similar to results seen in the overall population (34.9 vs 28.0 months, HR, 0.81 [95% CI, 0.64–1.03]), P = .09]) …”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of palbociclib plus endocrine therapy in North American women with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative metastatic breast cancer

Gelmon¹,

Cristofanilli

Rugo

et al. 2020

Breast J

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Palbociclib is a cyclin‐dependent kinase 4/6 inhibitor indicated for treatment of hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer in combination with endocrine therapy. We investigated the efficacy and safety of palbociclib in patients enrolled in North America during two‐phase 3 trials: PALOMA‐2 (n = 267, data cutoff: May 31, 2017) and PALOMA‐3 (n = 240, data cutoffs: April 13, 2018, for overall survival, October 23, 2015, for all other outcomes). In PALOMA‐2, treatment‐naïve postmenopausal patients with advanced breast cancer were randomized 2:1 to palbociclib (125 mg/d; 3 weeks on/1 week off [3/1]) plus letrozole (2.5 mg/d, continuous) or placebo plus letrozole. In PALOMA‐3, patients who progressed on prior endocrine therapy were randomized 2:1 to palbociclib (125 mg/d; 3/1) plus fulvestrant (500 mg, per standard of care) or placebo plus fulvestrant; pre/perimenopausal patients received ovarian suppression with goserelin. Palbociclib plus endocrine therapy prolonged median progression‐free survival vs placebo plus endocrine therapy in North American patients (PALOMA‐2: 25.4 vs 13.7 months, hazard ratio, 0.54 [95% CI, 0.40–0.74], P < .0001; PALOMA‐3: 9.9 vs 3.5 months, hazard ratio, 0.52 [95% CI, 0.38–0.72], P < .0001). Objective response and clinical benefit response rates were greater with palbociclib vs placebo in North American patients in both trials. While overall survival data are not yet mature for PALOMA‐2, median overall survival was increased in PALOMA‐3 (32.0 vs 24.7 months, hazard ratio, 0.75 [95% CI, 0.53–1.04]), though this did not reach statistical significance (P = .0869). Safety profiles in North American patients were similar to those of the overall populations; neutropenia was the most common treatment‐emergent adverse event. No new safety signals were observed. In summary, palbociclib plus endocrine therapy is an effective treatment option for North American women with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer.

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“…Palbociclib (125 mg, 28-day cycle with aromatase inhibitor) is used as the targeted therapy against ER + /HER2 − advanced and metastatic breast cancer in conjunction with hormone therapy. The open label PALOMA (Palbociclib: Ongoing Trials in the Management of Breast Cancer) clinical trials were designed recently with either aromatase inhibitor (letrozole) (PALOMA-1 or PALOMA-2 Trials) [111,112] or Fulvestrant hormone therapies (PALOMA-3 trails) [113]. An improvement in the overall survival of metastatic breast cancer patients was reported in PALOMA-3 phase III clinical trials.…”

Section: Cdk4/6 Inhibitormentioning

confidence: 99%

Drug repurposing for breast cancer therapy: Old weapon for new battle

Aggarwal

Verma

Aggarwal

et al. 2021

Seminars in Cancer Biology

104

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Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed. Current breast cancer therapyUnlike a decade ago, clinicians today have multiple choices for breast cancer treatment depending on the size, stage, grade, metastatic behavior, aggressiveness and intrinsic molecular subtyping of tumor, age, menopausal status, overall health, comorbidities, and preferences of the patient [9-13]. Chemotherapy, hormone therapy, immunotherapy, radiotherapy, and surgery are the common modalities for breast cancer [10,14]. Primary choice of treatment usually includes surgery with the aim of complete resection of the major tumor mass on the first hand. Breast conserving (lumpectomy) and breast reconstruction surgeries, mastectomy or lymph node dissections are performed initially in the breast cancer patients [15]. Surgery may be preceded with the systemic neoadjuvant therapies in order to shrink the tumor for effective surgery and to maximize breast conservation. For example, in HER2+ cases, Trastuzumab (Herceptin) and Pertuzumab (Perjeta)

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Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up

Cited by 302 publications

References 17 publications

CDK 4/6 inhibitor successful rechallenge after limiting hepatic toxicity

CDK 4/6 inhibitor successful rechallenge after limiting hepatic toxicity

Efficacy and safety of palbociclib plus endocrine therapy in North American women with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative metastatic breast cancer

Drug repurposing for breast cancer therapy: Old weapon for new battle

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