Two-Drug Regimens Dolutegravir/Lamivudine and Dolutegravir/Rilpivirine Are Effective with Few Discontinuations in US Real-World Settings: Results from the TANDEM Study.

INTRODUCTION: Dolutegravir/lamivudine (DTG/3TC) and dolutegravir/rilpivirine (DTG/RPV) are fixed-dose, complete, single-tablet, two-drug regimens (2DRs) indicated for HIV-1. DTG/3TC is approved for antiretroviral therapy (ART)-naive people with HIV-1 and virologically suppressed individuals to replace current ART; DTG/RPV is indicated for virologically suppressed individuals as a switch option. Virologic efficacy and effectiveness of these DTG-based 2DRs have been demonstrated in phase 3 clinical trials and real-world cohorts, primarily from Europe. This study characterized real-world use of DTG-based 2DRs for HIV-1 treatment in the USA. METHODS: TANDEM was a retrospective medical chart review across 24 US sites. Individuals aged ≥ 18 years who initiated DTG/3TC or DTG/RPV before September 30, 2020, with ≥ 6 months of follow-up were included. One cohort included ART-naive people who initiated DTG/3TC (n = 126), and two other cohorts included virologically suppressed (HIV-1 RNA < 50 copies/mL) people on stable ART regimens for ≥ 3 months before switch to either DTG/3TC (n = 192) or DTG/RPV (n = 151). Clinical characteristics, treatment history, and outcomes are described. RESULTS: Virologically suppressed individuals were older than those who were ART-naive, and the ART-naive cohort had higher proportions of individuals assigned male at birth and of Hispanic ethnicity. The most common healthcare provider-reported reason for choosing a DTG-based 2DR was avoidance of long-term toxicities (25-33% across cohorts), followed by simplification/streamlining of treatment. Among ART-naive people on DTG/3TC, 94% achieved virologic suppression after initiation, and 83% maintained suppression at last follow-up; discontinuation rate was < 1%. Among cohorts who switched to DTG-based 2DRs, 96% maintained virologic suppression on DTG/3TC and 93% on DTG/RPV; 2% on DTG/3TC and 3% on DTG/RPV discontinued. CONCLUSION: Motivation for selecting DTG-based 2DRs was primarily driven by a desire to avoid or manage toxicities and simplify treatment. Results demonstrate that DTG/3TC and DTG/RPV are effective in real-world settings, with few discontinuations, reflecting data from clinical trials.

Real-World Effectiveness of Dolutegravir/Lamivudine in People With HIV-1 in Test-and-Treat Settings or With High Baseline Viral Loads: TANDEM Study Subgroup Analyses.

INTRODUCTION: Dolutegravir/lamivudine (DTG/3TC) was first approved by the US Food and Drug Administration in 2019 for the treatment of antiretroviral therapy (ART)-naive people with HIV-1 based on results from the pivotal GEMINI-1/GEMINI-2 trials. Around that time, immediate initiation of treatment upon diagnosis was recommended in the US Department of Health and Human Services guidelines. Here we report results from 126 treatment-naive people with HIV-1 who initiated DTG/3TC as part of a test-and-treat strategy (n = 61) or with high baseline viral loads (HIV-1 RNA ≥ 100,000 copies/ml; n = 16) from the TANDEM study. METHODS: TANDEM was a US-based, retrospective chart review study that included a cohort of 126 individuals aged ≥ 18 years with no prior history of ART who initiated DTG/3TC before September 30, 2020, and had ≥ 6 months of follow-up. Test-and-treat was defined as ART initiation shortly after diagnosis without available viral load, CD4 + cell count, or HIV-1 resistance data. Outcomes included virologic suppression (HIV-1 RNA < 50 copies/ml; overall and by baseline viral load) and discontinuations. Analyses were descriptive. RESULTS: Among 61 individuals who initiated DTG/3TC in a test-and-treat setting (median [interquartile range (IQR)] treatment duration, 1.3 [0.9-1.7] years), 57 (93%) achieved virologic suppression, and 51 (84%) remained suppressed; 1 (< 1%) individual discontinued DTG/3TC due to persistent low-level viremia. The most common healthcare provider (HCP)-reported reason for initiating DTG/3TC was avoidance of long-term toxicities among individuals in the test-and-treat subgroup. Of 16 treatment-naive individuals with high baseline viral loads (median [IQR] treatment duration, 100,000-250,000 copies/ml: 1.2 [0.8-1.8] years; > 250,000 copies/ml: 1.0 [0.7-1.1] years), 14 (88%) achieved virologic suppression, 13 (81%) remained suppressed, and none discontinued DTG/3TC. Patient preference was the most common HCP-reported reason for initiating DTG/3TC in this subgroup. CONCLUSIONS: Results demonstrate real-world effectiveness of DTG/3TC, with few discontinuations, in people with HIV-1 in test-and-treat settings or with high baseline viral loads.

Real-world Treatment Patterns and Clinical Outcomes Associated With Palbociclib Combination Therapy: A Multinational, Pooled Analysis From the Ibrance Real World Insights Study.

PURPOSE: Palbociclib was the first cyclin-dependent kinase 4/6 inhibitor approved by the US Food and Drug Administration for use in combination with aromatase inhibitors (AIs) as initial endocrine-based therapy or with fulvestrant in postmenopausal women who previously received endocrine therapy based on data from randomized clinical trials. Real-world studies examining the effectiveness of palbociclib in large, diverse patient populations in routine clinical practice were needed. PATIENTS AND METHODS: Ibrance Real World Insights (IRIS) was a retrospective medical record review study of women with confirmed hormone receptor-positive, HER2-negative advanced/metastatic breast cancer treated with palbociclib plus an AI or with palbociclib plus fulvestrant according to approved indications. Participating physicians reviewed medical records of up to 16 sequentially presenting patients, collecting demographic and clinical data. Outcomes included objective response rates, progression-free rates, and survival rates overall and in patients stratified according to age, race and ethnicity, Eastern Cooperative Oncology Group (ECOG) performance status (PS), disease-free interval, visceral disease, liver metastases, bone-only metastases, and previous lines of therapy. FINDINGS: Data were abstracted by 417 physicians for 2954 patients in 13 countries; 1415 patients (47.9%) were ≥65 years of age, 369 patients (12.5%) had an ECOG PS ≥2 at initiation, and 835 patients (28.3%) were races other than White. The 12-month progression-free rate was 88% for palbociclib plus an AI and 79% for palbociclib plus fulvestrant; the 12-month survival rate was 96% in both groups. The objective response rates were 80% for palbociclib plus an AI and 75% for palbociclib plus fulvestrant. Palbociclib was similarly effective in most subgroups examined. IMPLICATIONS: Data from IRIS provide in-depth, real-world evidence for the use of palbociclib in a range of breast cancer populations in multiple countries. These data support the findings of the randomized PALOMA-2 and PALOMA-3 studies.

Treatment and disease management patterns for bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer in North America, Europe and Asia: A real-world data analysis.

Background: This study examined real-world treatment and management of bacillus Calmette-Guérin (BCG)-unresponsive patients across 3 continents, including patients unable or unwilling to undergo cystectomy. Materials and methods: Physicians actively involved in managing patients with nonmuscle invasive bladder cancer completed online case report forms for their 5 consecutive patients from the broad BCG-unresponsive population and a further 5 consecutive BCG-unresponsive patients who did not undergo cystectomy (in Japan, physicians provided a total of 5 patients across both cohorts). Results: Most patients had received 1 (37%) or 2 (24%) maintenance courses of BCG. Five or more maintenance BCG courses were received by patients in Japan (59%) and China (31%), while in Germany 76% of patients received only 1 course. Most patients became BCG-unresponsive during their first (44%) or second (22%) treatment course; in Germany, 77% became BCG-unresponsive during their first treatment course. Most countries did not provide another course of BCG after a patient first became unresponsive, whereas unresponsive patients in Japan and China were most likely to be retreated with BCG. "Untreated - on watch and wait" was the main treatment/management approach received post-BCG treatment for 42% or more of patients in most countries except China (39%) and the United States (36%). "Following treatment guidelines" was consistently the top reason for post-BCG treatment selection across all treatment options. Conclusions: This study confirmed the global unmet need for patients with nonmuscle invasive bladder cancer, and found that many patients experienced periods of no treatment after not responding to BCG therapy.

People living with moderate-to-severe COPD prefer improvement of daily symptoms over the improvement of exacerbations: a multicountry patient preference study.

Introduction: This patient preference study sought to quantify the preferences of people living with COPD regarding symptom improvement in the UK, USA, France, Australia and Japan. Methods: The inclusion criteria were people living with COPD aged 40 years or older who experienced ≥1 exacerbation in the previous year with daily symptoms of cough and excess mucus production. The study design included: 1) development of an attributes and levels grid through qualitative patient interviews; and 2) implementation of the main online quantitative survey, which included a discrete choice experiment (DCE) to allow assessment of attributes and levels using hypothetical health state profiles. Preference weights (utilities) were derived from the DCE using hierarchical Bayesian analysis. A preference simulator was developed that enabled different health state scenarios to be evaluated based on the predicted patient preferences. Results: 1050 people living with moderate-to-severe COPD completed the survey. All attributes were considered important when patients determined their preferences in the DCE. In a health state preference simulation, two hypothetical health states (comprising attribute levels) with qualitatively equivalent improvements in A) cough and mucus and B) shortness of breath (SOB) resulted in a clear preference for cough and mucus improved profile. When comparing two profiles with C) daily symptoms improved and D) exacerbations improved, there was a clear preference for the daily symptoms improved profile. Conclusions: People living with moderate-to-severe COPD prefer to reduce cough and mucus production together over improvement of SOB and would prefer to reduce combined daily symptoms over an improvement in exacerbations.

Real-world treatment patterns and clinical outcomes in patients receiving palbociclib combinations for HR+/HER2- advanced/metastatic breast cancer in Japan: Results from the IRIS study.

BACKGROUND: The incidence of breast cancer is rising in Japan, particularly in postmenopausal women. The CDK 4/6 inhibitor palbociclib has demonstrated efficacy in clinical studies in patients with hormone receptor-positive (HR+), human epidermal growth factor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). The Ibrance Real World Insights (IRIS) study (NCT03159195) collected real-world data for palbociclib-treated patients in several countries including Japan, where such data are currently scarce. METHODS: IRIS was a retrospective chart review study of patients with confirmed HR+/HER2- ABC/MBC receiving palbociclib according to approved indications in real-world clinical practice. In Japan, physicians each abstracted data from patient medical records for up to eight sequential patients treated with palbociclib plus an aromatase inhibitor (P+AI) or fulvestrant (P+F). Outcomes included progression-free rates (PFRs) and survival rates (SRs). RESULTS: Fifty-eight physicians abstracted data for 170 patients receiving palbociclib in the first (64.1%) or second or later line (35.9%), in combination with AI (51.2%) or fulvestrant (48.8%). Median follow-up was 10.4 months. Most patients were initiated on palbociclib 125 mg/d (P+AI, 63.2%; P+F, 78.3%). PFRs at 12 and 24 months were 76.2% and 52.6%, respectively, for P+AI and 71.6% and 65.6%, respectively for P+F. PFRs at 12 and 24 months were 85.4% and 66.5%, respectively, for first-line palbociclib combinations and 56.4% and 50.7%, respectively, for second- or later-line palbociclib combinations. CONCLUSIONS: In this analysis of the Japanese IRIS cohort, outcomes in terms of PFRs and SRs appear to be better with first- versus second or later-line palbociclib, regardless of the endocrine partner.

Multi-country clinical practice patterns, including use of biomarkers, among physicians' treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) fails in a considerable proportion of non-muscle invasive bladder cancer (NMIBC) patients despite treatment per recommended protocol. This real-world study aimed to understand the current patterns of treatment and disease management for the broad BCG-unresponsive NMIBC patient population, alongside collecting sufficient data on patients who do not undergo cystectomy. METHODS: This was a multicenter, retrospective survey of physicians treating BCG-unresponsive NMIBC patients. Data were collected in eight countries - France, Germany, Spain, Italy, United Kingdom, United States, China, and Japan - between January and May 2019. The study consisted of a short online physician survey and a retrospective chart review of eligible BCG-unresponsive NMIBC patients. Physicians abstracted chart data for the last 10 (five patients in Japan) eligible BCG-unresponsive NMIBC patients meeting the inclusion criteria, and the data were analysed for all countries combined using descriptive statistics. Country-specific analyses were also carried out, as appropriate. RESULTS: Overall, 508 physicians participated in the study. Almost one-quarter (22.9%) of physicians' current NMIBC patient caseload was BCG-unresponsive, whereby BCG therapy was no longer considered an option. Half of physicians (49.4%) did not regularly use biomarker tests in their practice, with particularly few physicians undertaking biomarker testing in Spain and Japan. Biomarker testing varied considerably, with the proportions of physicians selecting 'none' ranging from 11.4% in China to 70.3% in Japan. Physicians reported transurethral resection of the bladder tumor (TURBT) and BCG as the most common current treatments received by their patients. Chemotherapy and anti-PD-L1 treatment options were considered impactful new therapies by 94.7% and 90.0% of physicians surveyed in this study, respectively. CONCLUSIONS: The most common treatments received by patients in this study were TURBT and BCG. Emerging new treatments are driven by exploring biomarkers, but in real-world clinical practice only half of physicians or fewer regularly tested their NMIBC patients for biomarkers; PD-1/PD-L1 was the most common biomarker test used. Most physicians reported that, in addition to chemotherapy, anti-PD-L1 was an impactful new therapy.

Real-world treatment of patients with palbociclib for HR+/HER2-advanced/metastatic breast cancer: the Europe IRIS study.

Aim: To report the Europe Ibrance Real World Insights study findings. Methods: Physicians abstracted demographic/clinical characteristics, treatment and outcomes data for women with HR+/HER2- locally advanced breast cancer (ABC) or metastatic  breast cancer (MBC) receiving palbociclib + aromatase inhibitor (AI) or palbociclib + fulvestrant. Kaplan-Meier analysis estimated progression-free rates (PFRs) and survival rates (SRs). Results: 238 physicians abstracted data for 1723 patients. For patients (>90%) initiating at 125 mg/day, dose was reduced in 18.9% of palbociclib + AI and 12.3% of palbociclib + fulvestrant patients. At 12 months, PFR for palbociclib + AI was 88.1%, and SR was 97.3%; PFR for palbociclib + fulvestrant was 79.8%, and SR was 97.5%. Conclusion: Low dose-reduction rates and favorable PFRs and SRs suggest that palbociclib + AI/fulvestrant is well tolerated and effective for HR+/HER2- ABC/MBC in real-world clinical practice.

Lay abstract We describe findings of the Europe Ibrance Real World Insights study. Patients were women with a common type of breast cancer that had worsened but not spread or that had spread. Doctors collected medical information about the women and looked at their progress while on treatment. The treatment was either palbociclib + an aromatase inhibitor or palbociclib + fulvestrant. Two hundred thirty-eight doctors collected information on 1723 women. More than 90% of women started this treatment at a dose of 125 mg/day; the dose was reduced for fewer than 20% of women. At 12 months, more than 80% of women survived without their breast cancer worsening, and more than 97% of women survived. These good results suggest that this treatment is safe and effective for women with breast cancer that had worsened but not spread or that had spread.

Real-World Palbociclib Use in HR+/HER2- Advanced Breast Cancer in Canada: The IRIS Study.

BACKGROUND: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2- ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study (NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. METHODS: This retrospective chart review included women with HR+/HER2- ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan-Meier analysis. RESULTS: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. CONCLUSIONS: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.

Real-World Experience with Dolutegravir-Based Two-Drug Regimens.

BACKGROUND: Dolutegravir-based 2-drug regimens (DTG 2DRs) are now accepted as alternatives to 3-drug regimens for HIV antiretroviral treatment (ART); however, literature on physician drivers for prescribing DTG 2DR is sparse. This study evaluated treatment patterns of DTG 2DR components in clinical practice in the US. METHODS: This was a retrospective chart review in adult patients in care in the US with HIV-1 who received DTG 2DR prior to July 31, 2017, with follow-up until January 30, 2018. Primary objectives of the study were to determine reasons for patients initiating DTG 2DR and to describe the demographics and clinical characteristics. All analyses were descriptive. RESULTS: Overall, 278 patients received DTG 2DR (male: 70%; mean age: 56 years). Most patients were treatment experienced (98%), with a mean 13.5 years of prior ART. DTG was most commonly paired with darunavir (55%) or rilpivirine (27%). The most common physician-reported reasons for initiating DTG 2DR were treatment simplification/streamlining (30%) and avoidance of potential long-term toxicities (20%). Before starting DTG 2DR, 42% of patients were virologically suppressed; of those, 95% maintained suppression while on DTG 2DR. Of the 50% of patients with detectable viral load before DTG 2DR, 79% achieved and maintained virologic suppression on DTG 2DR during follow-up. There were no virologic data for 8% of patients prior to starting DTG 2DR. Only 15 patients discontinued DTG 2DR, of whom 4 (27%) discontinued due to virologic failure. CONCLUSIONS: Prior to commercial availability of the single-tablet 2DRs, DTG 2DR components were primarily used in treatment-experienced patients for treatment simplification and avoidance of long-term toxicities. Many of these patients achieved and maintained virologic suppression, with low discontinuation rates.

Burden of illness in not adequately controlled chronic hypoparathyroidism: Findings from a 13-country patient and caregiver survey.

OBJECTIVE: To address knowledge gaps regarding burdens associated with not adequately controlled chronic hypoparathyroidism. DESIGN: Global patient and caregiver survey. STUDY POPULATIONS: Patients with chronic hypoparathyroidism not adequately controlled on conventional therapy and their caregivers. MEASUREMENTS: Health-related quality of life (HRQoL) and health status were evaluated using the 36-item Short Form version 2 (SF-36 v2.0) and Five-Level EuroQoL 5 Dimensions (EQ-5D-5L) instruments, respectively. Hypoparathyroidism-associated symptoms were assessed by a disease-specific Hypoparathyroidism Symptom Diary and caregiver burden via the Modified Caregiver Strain Index (MCSI). RESULTS: Data were obtained from 398 patients and 207 caregivers. Patients' self-rated hypoparathyroidism-related symptom severity was none (3%), mild (32%), moderate (53%) or severe (12%). Per the Hypoparathyroidism Symptom Diary, patients reported moderate, severe or very severe symptoms of physical fatigue (73%), muscle cramps (55%), heaviness in limbs (55%) and tingling (51%) over a 7-day recall period. Impacts (rated 'somewhat' or 'very much') were reported by 84% of patients for ability to exercise, 78% for sleep, 75% for ability to work and 63% for family relationships. Inverse relationships were observed between patient self-rated overall symptom severity and HRQoL and health status assessment scores-the greater the symptom severity, the lower the SF-36 and EQ-5D-5L scores. Caregiver burden increased with patient self-rated symptom severity: none, 1.7 MCSI; mild, 5.4 MCSI; moderate, 9.5 MCSI; and severe, 12.5 MCSI. CONCLUSION: Patients with not adequately controlled hypoparathyroidism reported substantial symptoms and impacts. Greater patient symptom severity was associated with decreased patient HRQoL and health status assessments and increased caregiver burden.

Real-World Treatment Patterns and Clinical Outcomes in Patients Receiving Palbociclib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer in Argentina: The IRIS Study.

PURPOSE: The selective cyclin-dependent kinase 4/6 inhibitor palbociclib was approved in Argentina in 2015 for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) or metastatic breast cancer (MBC) based on phase III study results. The Ibrance Real World Insights (IRIS) study aims to evaluate palbociclib in patients with HR-positive/HER2-negative ABC or MBC in the real-world setting in multiple countries globally. Here we report results from patients enrolled in the IRIS study in Argentina. PATIENTS AND METHODS: This retrospective medical chart review study included postmenopausal women with confirmed HR-positive/HER2-negative ABC or MBC who were treated with palbociclib plus letrozole as first-line endocrine-based therapy or with palbociclib plus fulvestrant in women with disease progression after endocrine therapy. Participating physicians reviewed medical records of up to six patients each, collecting demographic and clinical data. Outcomes included progression-free and overall survival rates. RESULTS: Records were extracted for 162 patients in Argentina (palbociclib plus letrozole, n = 105 [65%]; palbociclib plus fulvestrant, n = 57 [35%]). The 6-month progression-free survival rate was 94% for patients treated with palbociclib plus letrozole and 95% for patients treated with palbociclib plus fulvestrant; 85% and 80% of patients treated with palbociclib plus letrozole were progression free at 12 and 18 months, respectively. Six-month survival rates were 98% for palbociclib plus letrozole and 98% for palbociclib plus fulvestrant; 93% and 89% of patients treated with palbociclib plus letrozole were alive at 12 and 18 months, respectively. CONCLUSION: Results from this first real-world evaluation of clinical outcomes in Argentina suggest that palbociclib plus letrozole or fulvestrant delivers favorable effectiveness, as measured by progression-free and overall survival rates.