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Frontiers in Endocrinology 2021Letrozole, an aromatase inhibitor that blocks estrogen synthesis by inhibiting the final step of the estrogen biosynthetic pathway, has been used in the applications of... (Review)
Review
Letrozole, an aromatase inhibitor that blocks estrogen synthesis by inhibiting the final step of the estrogen biosynthetic pathway, has been used in the applications of a wide range of infertility settings. It has been more than 20 years since the initial clinical trial of letrozole for ovulation induction. In light of the accumulating clinical and basic evidence, the efficacy and safety of letrozole have been identified. This mini review focuses on our current knowledge of the applications and mechanisms of letrozole for female infertility and various questions are put forward about how letrozole could be more effectively used.
Topics: Aromatase Inhibitors; Female; Humans; Infertility, Female; Letrozole; Treatment Outcome
PubMed: 34220713
DOI: 10.3389/fendo.2021.676133 -
Taiwanese Journal of Obstetrics &... Jan 2022Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism. The treatment... (Review)
Review
Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism. The treatment in PCOS is mainly symptomatic and involves lifestyle interventions and medications such as Metformin, Oral contraceptives and Antiandrogens. However, the management of PCOS is challenging and current interventions are not able to deal with outcomes of this syndrome. This review encompasses latest pharmacotherapeutic and non-pharmacotherapeutic interventions currently in use to tackle various symptomatic contentions in PCOS. Our focus has been mainly on novel therapeutic modalities for treatment/management of PCOS, like use of newer insulin sensitizers viz., Inositols, Glucagon-like peptide-1(GLP-1) agonists, Dipeptidyl pepdidase-4 (DPP-4) inhibitors, and sodium-glucose transport protein 2 (SGLT2) inhibitors. Also, evidence suggesting the use of vitamin D, statins, and Letrozole as emerging therapies in PCOS have been summarized in this review. Additionally, novel cosmetic techniques like electrolysis, laser and use of topically applied eflornithine to tackle the most distressing feature of facial hirsutism associated with PCOS, non-pharmacological therapy like acupuncture and the role of herbal medicine in PCOS management have also been discussed.
Topics: Acupuncture; Anovulation; Eflornithine; Female; Herbal Medicine; Hirsutism; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperandrogenism; Hypoglycemic Agents; Laser Therapy; Letrozole; Metformin; Polycystic Ovary Syndrome; Vitamin D
PubMed: 35181044
DOI: 10.1016/j.tjog.2021.11.009 -
Gynecological Endocrinology : the... Oct 2021Infertility concerns 15% of the couples. Management of female infertility requires a complete history of the patient followed by a physical, gynecological and endocrine... (Review)
Review
Infertility concerns 15% of the couples. Management of female infertility requires a complete history of the patient followed by a physical, gynecological and endocrine examination. Infertility etiology will be investigated thanks to different tests including ovarian function and reserve assessment, search for uterine abnormalities and evaluation of tubal permeability. Polycystic ovarian syndrome (PCOS) is a predominant cause of infertility and a common gyne-endocrine disorder affecting 7 to 15% of women in reproductive age. Behavioral, medical and surgical treatments have been evaluated in order to improve the fertility of women with PCOS. Lifestyle modifications (stop smoking, physical exercise and weight loss when necessary) are of the utmost importance. Clomiphene citrate remains the first line of medical treatment of infertility in women with PCOS in absence of other male or female causes of infertility. Use of metformin solely for infertility is not recommended in absence of metabolic anomaly and new treatment as myoinositol is emerging. Surgical techniques aiming to enhance ovulation and pregnancy rate are an option when medical treatment failed. Ovarian drilling by laparoscopy or by transvaginal hydrolaparoscopy is taking a larger place in the treatment of infertility. maturation and fertilization remain the third-line of treatment in PCOS.
Topics: Anti-Mullerian Hormone; Bariatric Surgery; Clomiphene; Female; Gonadotropins; Humans; Infertility, Female; Letrozole; Life Style; Ovary; Polycystic Ovary Syndrome; Pregnancy; Reproductive Techniques, Assisted
PubMed: 34338572
DOI: 10.1080/09513590.2021.1958310 -
Annals of Oncology : Official Journal... Jul 2018The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus... (Randomized Controlled Trial)
Randomized Controlled Trial
Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer.
BACKGROUND
The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Here, we report updated efficacy and safety data, together with exploratory biomarker analyses, from the MONALEESA-2 study.
PATIENTS AND METHODS
A total of 668 postmenopausal women with HR+, HER2- recurrent/metastatic breast cancer were randomized (1 : 1; stratified by presence/absence of liver and/or lung metastases) to ribociclib (600 mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole. The primary end point was locally assessed PFS. The key secondary end point was overall survival (OS). Other secondary end points included overall response rate (ORR) and safety. Biomarker analysis was an exploratory end point.
RESULTS
At the time of the second interim analysis, the median duration of follow-up was 26.4 months. Median PFS was 25.3 months [95% confidence interval (CI) 23.0-30.3] for ribociclib plus letrozole and 16.0 months (95% CI 13.4-18.2) for placebo plus letrozole (hazard ratio 0.568; 95% CI 0.457-0.704; log-rank P = 9.63 × 10-8). Ribociclib treatment benefit was maintained irrespective of PIK3CA or TP53 mutation status, total Rb, Ki67, or p16 protein expression, and CDKN2A, CCND1, or ESR1 mRNA levels. Ribociclib benefit was more pronounced in patients with wild-type versus altered receptor tyrosine kinase genes. OS data remain immature, with 116 deaths observed; 50 in the ribociclib arm and 66 in the placebo arm (hazard ratio 0.746; 95% CI 0.517-1.078). The ORR was 42.5% versus 28.7% for all patients treated with ribociclib plus letrozole versus placebo plus letrozole, respectively, and 54.5% versus 38.8%, respectively, for patients with measurable disease. Safety results, after a further 11.1 months of follow-up, were comparable with those reported at the first analysis, with no new or unexpected toxicities observed, and no evidence of cumulative toxicity.
CONCLUSIONS
The improved efficacy outcomes and manageable tolerability observed with first-line ribociclib plus letrozole are maintained with longer follow-up, relative to letrozole monotherapy.
CLINICAL TRIALS NUMBER
NCT01958021.
Topics: Aged; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Double-Blind Method; Female; Follow-Up Studies; Humans; Letrozole; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Recurrence, Local; Prognosis; Purines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Rate
PubMed: 29718092
DOI: 10.1093/annonc/mdy155 -
JAMA Oncology Dec 2021The cyclin-dependent kinase 4 and 6 inhibitor palbociclib in combination with letrozole has become a standard first-line treatment for patients with endocrine-sensitive,... (Randomized Controlled Trial)
Randomized Controlled Trial
Fulvestrant-Palbociclib vs Letrozole-Palbociclib as Initial Therapy for Endocrine-Sensitive, Hormone Receptor-Positive, ERBB2-Negative Advanced Breast Cancer: A Randomized Clinical Trial.
IMPORTANCE
The cyclin-dependent kinase 4 and 6 inhibitor palbociclib in combination with letrozole has become a standard first-line treatment for patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer. Meanwhile, the antiestrogen fulvestrant was shown to be superior to anastrozole in the absence of cyclin-dependent kinase 4 and 6 inhibition for this patient population.
OBJECTIVE
To assess whether fulvestrant is superior to letrozole when combined with palbociclib in the first-line scenario.
DESIGN, SETTING, AND PARTICIPANTS
In this international, randomized, open-label, phase 2 clinical study conducted from July 30, 2015, to January 8, 2018, patients with hormone receptor-positive, ERBB2-negative advanced breast cancer with no prior therapy in the metastatic setting and endocrine-sensitive criteria were recruited from 47 centers in 7 countries. Data were analyzed from February 11 to May 15, 2020.
INTERVENTIONS
Patients were randomly assigned (1:1 ratio) to receive palbociclib with either fulvestrant or letrozole. Stratification factors were type of disease presentation (de novo vs recurrent) and the presence of visceral involvement (yes vs no).
MAIN OUTCOMES AND MEASURES
The primary end point was investigator-assessed progression-free survival determined by Response Evaluation Criteria in Solid Tumors, version 1.1.
RESULTS
A total of 486 women (median age, 63 years [range, 25-90 years]; 3 Asian women [0.6%]; 4 Black women [0.8%]; 461 White women [94.9%]; 18 women of unknown race [3.7%]) were randomized (243 to fulvestrant-palbociclib and 243 to letrozole-palbociclib). Median investigator-assessed progression-free survival was 27.9 months (95% CI, 24.2-33.1 months) in the fulvestrant-palbociclib group vs 32.8 months (95% CI, 25.8-35.9 months) in the letrozole-palbociclib group (hazard ratio, 1.13; 95% CI, 0.89-1.45; P = .32). This result was consistent across the stratification factors. No significant differences were observed in objective response rate (46.5% vs 50.2%) and 3-year overall survival rate (79.4% vs 77.1%) for fulvestrant-palbociclib and letrozole-palbociclib, respectively. Grade 3-4 adverse events were comparable among treatment groups, and no new safety signals were identified. No treatment-related deaths were reported.
CONCLUSIONS AND RELEVANCE
Although fulvestrant-palbociclib demonstrated significant antitumor activity, this randomized clinical trial failed to identify an improvement in progression-free survival with this regimen over letrozole-palbociclib in patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02491983.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Fulvestrant; Humans; Letrozole; Middle Aged; Piperazines; Pyridines; Receptor, ErbB-2
PubMed: 34617955
DOI: 10.1001/jamaoncol.2021.4301 -
Breast Cancer Research and Treatment Apr 2019In the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
PURPOSE
In the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P < 0.001]. Herein, we report results overall and by subgroups with extended follow-up.
METHODS
In this double-blind, phase 3 study, post-menopausal women with ER+/HER2- ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).
RESULTS
After a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib-letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P < 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib-letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients' quality of life was maintained.
CONCLUSIONS
With approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2- ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Double-Blind Method; Female; Humans; Letrozole; Piperazines; Postmenopause; Pyridines; Quality of Life; Receptor, ErbB-2; Receptors, Estrogen; Treatment Outcome
PubMed: 30632023
DOI: 10.1007/s10549-018-05125-4 -
Fertility and Sterility Mar 2019To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic ovary syndrome (PCOS).
DESIGN
Open-label randomized controlled trial.
SETTING
Academic medical center using two clinic sites.
PATIENT(S)
Women 18-40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility.
INTERVENTIONS(S)
Participants were randomized in a 1:1 ratio, stratified by age and body mass index, to either 2.5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3-7 for one treatment cycle.
MAIN OUTCOME MEASURE(S)
Ovulation defined as mid-luteal serum progesterone concentration ≥3 ng/mL.
RESULT(S)
Seventy patients were randomized: 35 to letrozole alone and 35 to letrozole and CC. Results were analyzed according to the intention-to-treat principle. Women who received the combination of letrozole and CC had a statistically higher ovulation rate compared with those who received letrozole alone (27 of 35 women [77%] vs. 15 of 35 women [43%]). There were no serious adverse events or multiple-gestation pregnancies in either group. The side-effects profile was similar in the two treatment groups.
CONCLUSION(S)
The combination of letrozole and CC was associated with a higher ovulation rate compared with letrozole alone in women with infertility and PCOS. Further studies are needed to evaluate the effect on live birth rate.
CLINICAL TRIAL REGISTRATION NUMBER
NCT02802865.
Topics: Adolescent; Adult; Age Factors; Biomarkers; Body Mass Index; Clomiphene; Female; Fertility; Fertility Agents, Female; Humans; Infertility, Female; Iowa; Letrozole; Live Birth; Ovulation; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Progesterone; Treatment Outcome; Young Adult
PubMed: 30683591
DOI: 10.1016/j.fertnstert.2018.11.030 -
Journal of Clinical Oncology : Official... Jan 2019Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years.
PATIENTS AND METHODS
BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported.
RESULTS
Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up.
CONCLUSION
Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.
Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Female; Humans; Letrozole; Middle Aged; Postmenopause; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen
PubMed: 30475668
DOI: 10.1200/JCO.18.00440 -
The Cochrane Database of Systematic... Sep 2022Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of women worldwide and often leads to anovulatory infertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI, letrozole, is at least as effective as the first-line treatment clomiphene citrate (CC), a selective oestrogen receptor modulator (SERM).
OBJECTIVES
To evaluate the effectiveness and safety of AIs (letrozole) (with or without adjuncts) compared to SERMs (with or without adjuncts) for infertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination.
SEARCH METHODS
We searched the following sources, from their inception to 4 November 2021, to identify relevant randomised controlled trials (RCTs): the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and PsycINFO. We also checked reference lists of relevant trials, searched the trial registers and contacted experts in the field for any additional trials. We did not restrict the searches by language or publication status.
SELECTION CRITERIA
We included all RCTs of AIs used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted the data and assessed risks of bias using RoB 1. We pooled trials where appropriate using a fixed-effect model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes, and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth rate and OHSS rate. Secondary outcomes were clinical pregnancy, miscarriage and multiple pregnancy rates. We assessed the certainty of the evidence for each comparison using GRADE methods.
MAIN RESULTS
This is a substantive update of a previous review; of six previously included trials, we excluded four from this update and moved two to 'awaiting classification' due to concerns about validity of trial data. We included five additional trials for this update that now includes a total of 41 RCTs (6522 women). The AI, letrozole, was used in all trials. Letrozole compared to SERMs with or without adjuncts followed by timed intercourse Live birth rates were higher with letrozole (with or without adjuncts) compared to SERMs followed by timed intercourse (OR 1.72, 95% CI 1.40 to 2.11; I = 0%; number needed to treat for an additional beneficial outcome (NNTB) = 10; 11 trials, 2060 participants; high-certainty evidence). This suggests that in women with a 20% chance of live birth using SERMs, the live birth rate in women using letrozole with or without adjuncts would be 27% to 35%. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs (0.5% in both arms: risk difference (RD) -0.00, 95% CI -0.01 to 0.01; I = 0%; 10 trials, 1848 participants; high-certainty evidence). There is evidence for a higher pregnancy rate in favour of letrozole (OR 1.69, 95% CI 1.45 to 1.98; I = 0%; NNTB = 10; 23 trials, 3321 participants; high-certainty evidence). This suggests that in women with a 24% chance of clinical pregnancy using SERMs, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 32% to 39%. There is little or no difference between treatment groups in the rate of miscarriage per pregnancy (25% with SERMs versus 24% with letrozole: OR 0.94, 95% CI 0.66 to 1.32; I = 0%; 15 trials, 736 participants; high-certainty evidence) and multiple pregnancy rate (2.2% with SERMs versus 1.6% with letrozole: OR 0.74, 95% CI 0.42 to 1.32; I = 0%; 14 trials, 2247 participants; high-certainty evidence). However, a funnel plot showed mild asymmetry, indicating that some trials in favour of SERMs might be missing. Letrozole compared to laparoscopic ovarian drilling (LOD) One trial reported very low-certainty evidence that live birth rates may be higher with letrozole compared to LOD (OR 2.07, 95% CI 0.99 to 4.32; 1 trial, 141 participants; very low-certainty evidence). This suggests that in women with a 22% chance of live birth using LOD with or without adjuncts, the live birth rate in women using letrozole with or without adjuncts would be 24% to 47%. No trial reported OHSS rates. Due to the low-certainty evidence we are uncertain if letrozole improves pregnancy rates compared to LOD (OR 1.47, 95% CI 0.95 to 2.28; I² = 0%; 3 trials, 367 participants; low-certainty evidence). This suggests that in women with a 29% chance of clinical pregnancy using LOD with or without adjuncts, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 28% to 45%. There seems to be no evidence of a difference in miscarriage rates per pregnancy comparing letrozole to LOD (OR 0.65, 95% CI 0.22 to 1.92; I² = 0%; 3 trials, 122 participants; low-certainty evidence). This also applies to multiple pregnancies (OR 3.00, 95% CI 0.12 to 74.90; 1 trial, 141 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Letrozole appears to improve live birth rates and pregnancy rates in infertile women with anovulatory PCOS, compared to SERMs, when used for ovulation induction, followed by intercourse. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs. There was high-certainty evidence of no difference in miscarriage rate and multiple pregnancy rate. We are uncertain if letrozole increases live birth rates compared to LOD. In this update, we added good quality trials and removed trials with concerns over data validity, thereby upgrading the certainty of the evidence base.
Topics: Abortion, Spontaneous; Anovulation; Aromatase Inhibitors; Clomiphene; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Live Birth; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Selective Estrogen Receptor Modulators
PubMed: 36165742
DOI: 10.1002/14651858.CD010287.pub4 -
Annals of Oncology : Official Journal... Apr 2018Patient-reported outcomes are integral in benefit-risk assessments of new treatment regimens. The PALOMA-2 study provides the largest body of evidence for... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patient-reported outcomes are integral in benefit-risk assessments of new treatment regimens. The PALOMA-2 study provides the largest body of evidence for patient-reported health-related quality of life (QOL) for patients with metastatic breast cancer (MBC) receiving first-line endocrine-based therapy (palbociclib plus letrozole and letrozole alone).
PATIENTS AND METHODS
Treatment-naïve postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) MBC were randomized 2 : 1 to palbociclib plus letrozole (n = 444) or placebo plus letrozole (n = 222). Patient-reported outcomes were assessed at baseline, day 1 of cycles 2 and 3, and day 1 of every other cycle from cycle 5 using the Functional Assessment of Cancer Therapy (FACT)-Breast and EuroQOL 5 dimensions (EQ-5D) questionnaires.
RESULTS
As of 26 February 2016, the median duration of follow-up was 23 months. Baseline scores were comparable between the two treatment arms. No significant between-arm differences were observed in change from baseline in FACT-Breast Total, FACT-General Total, or EQ-5D scores. Significantly greater improvement in pain scores was observed in the palbociclib plus letrozole arm (-0.256 versus -0.098; P = 0.0183). In both arms, deterioration of FACT-Breast Total score was significantly delayed in patients without progression versus those with progression and patients with partial or complete response versus those without. No significant difference was observed in FACT-Breast and EQ-5D index scores in patients with and without neutropenia.
CONCLUSIONS
Overall, women with MBC receiving first-line endocrine therapy have a good QOL. The addition of palbociclib to letrozole maintains health-related QOL and improves pain scores in treatment-naïve postmenopausal patients with ER+/HER2- MBC compared with letrozole alone. Significantly greater delay in deterioration of health-related QOL was observed in patients without progression versus those who progressed and in patients with an objective response versus non-responders. ClinicalTrials.gov: NCT01740427 (https://clinicaltrials.gov/ct2/show/NCT01740427).
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Double-Blind Method; Female; Humans; Letrozole; Middle Aged; Piperazines; Placebos; Postmenopause; Pyridines; Quality of Life
PubMed: 29360932
DOI: 10.1093/annonc/mdy012