ATV/r-based regimens: durable virological suppression and good tolerability as switch strategy from NNRTI-containing regimens in a real-life cohort

Abstract Objectives Dolutegravir is widely prescribed owing to its potent antiviral activity, high genetic barrier and good tolerability. The aim of this study was to characterize dolutegravir’s pharmacokinetic profile and variability in a real-life setting and to identify individual factors and co-medications affecting dolutegravir disposition. Methods A population pharmacokinetic model was developed using NONMEM®. Relevant demographic factors, clinical factors and co-medications were tested as potential covariates. Simulations based on the final model served to compare expected dolutegravir concentrations under standard and alternative dosage regimens in the case of drug–drug interactions. Results A total of 620 dolutegravir plasma concentrations were collected from 521 HIV-infected individuals under steady-state conditions. A one-compartment model with first-order absorption and elimination best characterized dolutegravir pharmacokinetics. Typical dolutegravir apparent clearance (CL/F) was 0.93 L/h with 32% between-subject variability, the apparent volume of distribution was 20.2 L and the absorption rate constant was fixed to 2.24 h−1. Older age, higher body weight and current smoking were associated with higher CL/F. Atazanavir co-administration decreased dolutegravir CL/F by 38%, while darunavir modestly increased CL/F by 14%. Rifampicin co-administration showed the largest impact on CL/F. Simulations suggest that average dolutegravir trough concentrations are 63% lower after 50 mg/12h with rifampicin compared with a standard dosage of 50 mg/24h without rifampicin. Average trough concentrations after 100 mg/24h and 100 mg/12h with rifampicin are 92% and 25% lower than the standard dosage without rifampicin, respectively. Conclusions Patients co-treated with dolutegravir and rifampicin might benefit from therapeutic drug monitoring and individualized dosage increase, up to 100 mg/12 h in some cases.

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Safety and efficacy of abiraterone acetate (AA) in patients aged 75 or more with metastatic castration-resistant prostate cancer (mCRPC) in both pre-chemotherapy or post-chemotherapy settings: Real-life experience from thirteen Italian centers.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.209 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 209-209

Author(s):

Zuzana Sirotova ◽

Giulia Courthod ◽

Alfredo Tartarone ◽

Orazio Caffo ◽

Francesca Maines ◽

...

Keyword(s):

Prostate Cancer ◽

Elderly Patients ◽

Liver Toxicity ◽

Real Life ◽

Castration Resistant Prostate Cancer ◽

Synthesis Inhibitor ◽

Good Tolerability ◽

Efficient Treatment ◽

Androgen Synthesis ◽

Docetaxel Group

209 Background: Prostate cancer affects mainly elderly patients (pts) that have different comorbidities. AA is a selective androgen synthesis inhibitor that showed the efficacy in either chemotherapy (CT) naive pts or those pretreated with docetaxel. Its oral administration and good tolerability make it a manegeable treatment for elderly mCRPC pts. Methods: We collected retrospectively data regarding mCRPC pts aged ≥75 years treated with AA in 13 Italian Centers since April 2013. The median age was 79 years (r. 75-90) with 48% of pts being octagerians. Post CT pts had more extensive disease, higher baseline PSA and ECOG PS. Nearly all the pts had comorbidities, the most frequent being hypertension present in 146 pts (58%), 43 pts (17%) had diabetes type II. We evaluated duration of the AA treatment, overall response rate (ORR), 50% PSA decline, time to progression (TTP) and overall survival (OS). We reported all toxicities observed. Results: A total of 252 pts ,147 pre treated with docetaxel and 105 chemo naive, were included. Median duration of treatment with AA was 8,6 months in post CT and 11,5 in CT naive pts. ORR was 35,3% in pre docetaxel and 27,4% in post docetaxel group. 64 pts (65%) and 51 pts (46%) obtained 50% PSA reduction in pre and post docetaxel group, respectively. Median TTP was 8,6 in post docetaxel and 11,9 in CT naive pts. We observed a median OS of 13,8 months in post CT group while for CT naive pts data were not yet mature. AA was well tolerated with only 8 pts (3,2%) who discontinued treatment due to toxicity, while in 4 pts (1,6%) temporary dose reductions were performed. The most frequent G3 toxicities were hypertension and liver toxicity with 4 pts (1,6%) and 5 pts (2%), respectively. After progressing on AA, 85 pts (34%) received at least one subsequent treatment. 40 pts (15,9%) are still on treatment with AA. Conclusions: Even if almost all the pts reported comorbidities at AA start and 72 pts (28,6%) had PS ECOG 2, only a small proportion of them discontinued the treatment due to toxicity confirming that AA is well tolerated and efficient treatment also for elderly patients.

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Sublingual Immunotherapy with a Five-Grass Pollen Tablet in Adult Patients with Allergic Rhinitis: An Open, Prospective, Noninterventional, Multicenter Study

BioMed Research International ◽

10.1155/2015/584291 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Oliver Pfaar ◽

Heinz-Gerd Richter ◽

Ludger Klimek ◽

Jochen Sieber ◽

Meike Hadler ◽

...

Keyword(s):

Medical Practice ◽

Grass Pollen ◽

Randomized Clinical Trials ◽

Sublingual Immunotherapy ◽

Symptom Relief ◽

Large Population ◽

Real Life ◽

Good Tolerability ◽

Symptomatic Medication ◽

Patient Reported

Background. Although the safety and efficacy of sublingual immunotherapy (SLIT) with a five-grass pollen tablet have been demonstrated in randomized clinical trials (RCTs), these outcomes must always be evaluated in real-life medical practice.Methods. In a prospective, open-label, noninterventional, “real-life” study in Germany, we evaluated the safety, tolerability, and effectiveness of SLIT with a five-grass pollen tablet in adults with grass-pollen-induced allergic rhinoconjunctivitis.Results. 808 adults were enrolled between September 2008 and December 2009. 35.3% of the participants experienced at least one adverse drug reaction (ADR), the most common of which were mild-to-moderate gastrointestinal and respiratory disorders. Serious ADRs considered causally related to SLIT treatment occurred in four patients. Overall, the five-grass pollen tablet was considered to have good or very good tolerability by most investigators and patients. Treatment was associated with the relief of nasal, ocular, and bronchial symptoms and decreased symptomatic medication use. However, interpretation of clinical improvements was limited by lower atmospheric grass pollen levels during the study season (relative to the preceding season).Conclusions. In a large population of patients treated in real-life medical practice, SLIT with a five-grass pollen tablet was safe and well tolerated. The patient-reported symptom relief suggests that SLIT was associated with clinical benefits.

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Effects of A Long-Term Use of Carbocysteine on Frequency and Duration of Exacerbations in Patients with Bronchiectasis

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.697 ◽

2019 ◽

Vol 7 (23) ◽

pp. 4030-4035

Author(s):

Jordan Minov ◽

Sasho Stoleski ◽

Tatjana Petrova ◽

Kristin Vasilevska ◽

Dragan Mijakoski ◽

...

Keyword(s):

Real Life ◽

Hospital Treatment ◽

Control Group ◽

Good Tolerability ◽

Life Study ◽

Positive Effects ◽

Mucus Clearance ◽

Appropriate Treatment ◽

And Control

BACKGROUND: The failure of mucus clearance in bronchiectasis can be improved by chest physiotherapy or/and mucoactive agents. AIM: To assess the effects of long-term use of carbocysteine on frequency and duration of exacerbations in patients with bronchiectasis. METHODS: We performed an observational, non-randomized, open study (a real-life study) including 64 patients with bronchiectasis divided into two groups, examined group (EG) and control group (CG). All participants were treated with appropriate treatment for the stable disease, but in the study, subjects of EG two capsules 375 mg carbocysteine three times a day was added over three months. Daily diary cards realised collection of data regarding the occurrence and duration of exacerbation in all study subjects. RESULTS: Over the study period 43 exacerbations were documented, 17 in the EG and 26 in the CG, 10 (23.4%) of which required hospital treatment (four in the EG [23.5%] and six in the CG [23.1%]). A mean number of exacerbations over the study period was significantly lower in the EG (0.5 ± 0.1) as compared to their mean number in the CG (0.8 ± 0.2) (P = 0.0000). Mean duration of exacerbations expressed in days needed for complete resolution of symptoms or return of the symptoms to their baseline severity in the EG was significantly shorter than the mean duration of exacerbations in the CG (10.1 ± 2.6 vs 12.8 ± 2.1; P = 0.0000). The frequency of adverse effects, i.e. mild gastrointestinal manifestations and headache which did not require discontinuation of the treatment, in the EG during the study period was 15.6%. CONCLUSION: Our findings indicated positive effects of carbocysteine regarding the frequency and duration of exacerbations, as well as its good tolerability in the patients with bronchiectasis.

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Characteristics of patients with psoriatic arthritis treated with ustekinumab. Evidence from real-life clinical practice

Medical Council ◽

10.21518/2079-701x-2020-21-274-283 ◽

2021 ◽

pp. 274-283

Author(s):

Yu. L. Korsakova ◽

E. Yu. Loginova ◽

E. E. Gubar ◽

T. V. Korotaeva

Keyword(s):

Psoriatic Arthritis ◽

Clinical Laboratory ◽

Real Life ◽

Circulatory System ◽

Latent Tuberculosis ◽

Endocrine System ◽

Gastrointestinal Diseases ◽

Good Tolerability ◽

Viral Hepatitis C ◽

Circulatory System Diseases

Introduction. Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease characterised by involvement of the skin, nail plates, joints, spine and entheses in the inflammatory process. The IL-12/IL-23 inhibitor ustekinumab (UST) is increasingly being used in psoriasis (Ps) and PsA.Aim of the study. To analyze patients with PsA who were under inpatient treatment in the V.A. Nasonova Scientific Research Institute of Rheumatology and Radiology and who were prescribed UST during the period from 2018 to 2020.Material and methods. UST was administered to 17 patients with PsA (9 women and 8 men), mean age was 46.4 ± 11.3 years. Duration of PsA course was 11 ± 10.5 years. Patients underwent clinical, laboratory and instrumental examination, BSA and PASI, DAPSA and BASDAI indices were determined.Results. Patients predominantly had widespread Ps (BSA 18.2 ± 15.9%). Erosive arthritis was present in 94.1% of patients, and sacroiliitis was detected in 100% of patients. PsA activity was high (DAPSA = 44.9 ± 20.9, BASDAI = 6.2 ± 1.5).94% of patients had two or more comorbidities. Circulatory system diseases were observed in 82.4% of patients, liver diseases in 29.5%, gastrointestinal diseases in 47%, endocrine system diseases in 17.6%, viral hepatitis C in 23.5%, latent tuberculosis infection in 17.6%, and joint surgery was performed in 11.2% of patients. The clinical example presented in the article demonstrates good tolerability of UST in a patient with PsA with a number of comorbidities and the possibility to increase the dose of UST from 45 to 90 mg in case of ineffective therapy.Conclusions. The safety profile of UST is good, and it can be administered to patients with cardiovascular diseases, obesity, various infections, including latent tuberculosis, etc.

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Safety and Effectiveness of Venetoclax/Rituximab in Bcri-Naïve and Bcri-Exposed Patients with Relapsed/Refractory CLL Under Real-Life Conditions - Data from the Observational Verve Study

Blood ◽

10.1182/blood-2021-145555 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3735-3735

Author(s):

Davide Rossi ◽

Holger Hebart ◽

Christoph Losem ◽

Thomas Wolff ◽

Xenia Schmidt ◽

...

Keyword(s):

Risk Factors ◽

Real World ◽

Research Funding ◽

Tp53 Mutation ◽

Real Life ◽

Exposed Group ◽

Lymphocytic Leukemia ◽

Good Tolerability ◽

Overall Response

Abstract Background In clinical trials, venetoclax has shown high efficacy and good tolerability in patients with chronic lymphocytic leukemia (CLL). Retrospective cohort studies have examined outcomes with venetoclax in B-cell receptor pathway inhibitor (BCRi) naïve and exposed patients with relapsed/refractory (R/R) CLL in the real world setting. However, prospective real-world data on the sequencing of new agents in the R/R setting are limited. The prospective non-interventional observational study VeRVe is assessing effectiveness, safety, and quality of life in CLL patients treated with venetoclax in Austria, Germany, and Switzerland according to local label. Here we report outcomes in patients treated with venetoclax in combination with rituximab (VenR) in BCRi-naïve and BCRi-exposed patients. Methods Adult patients with CLL requiring therapy treated with VenR according to local label were included in this analysis. Patient visits are scheduled at the physician's discretion and according to clinical practice. Study documentation is possible at baseline, weekly during ramp-up, monthly until the end of 6 months and 3-monthly afterwards up to a maximum of 3 years. Response assessment according to iwCLL criteria can be documented at the end of ramp-up, after 3, 12, and 24 months. Analyses were performed for subgroups of BCRi-naïve and BCRi-exposed patients. Results Until April 26, 2021, 94 patients treated with VenR had been enrolled in the ongoing study and had received at least one dose of venetoclax (safety population). For 72 patients, treatment response had been documented at least once (effectiveness population). Enrolled patients had a median of 1 (range 1-10) previous lines of therapy. 57 patients (61%) had previously been treated with chemoimmunotherapy (CIT) and were BCRi-naïve, 32 patients (34%) had received at least one prior BCRi and 7 (7%) had received other prior treatment options. BCRi-naïve patients had a median of 1 prior therapies (range 1-4), while BCRi-exposed patients had received a median of 3 prior therapies (range 1-10). Risk factors were more common in the BCRi-exposed group (38% of patients had a documented del(17p), 34% a TP53 mutation, and 41% an unmutated IGHV status) in comparison to the BCRi-naïve group (14% del(17p), 16% TP53 mutation and 40% unmutated IGHV). Median age at baseline was 72 and 71 years for BCRi-naïve and BCRi-exposed patients, respectively. 65% vs. 84% of BCRi-naive and BCRi-exposed patients had at least one comorbidity. In the BCRi-exposed group, 29 patients (91%) had a BCRi as last prior therapy before VenR initiation with a median duration of prior BCRi therapy of 18 months (range 1 - 61 month). Most frequent reasons for discontinuation of prior BCRi therapy were AE/SAE (11 patients) and disease progression (12 patients). The reported best overall response at 12 months after VenR initiation was 83% (CR+CRi 55%; PR: 28%) for BCRi-naïve and 85% (CR+CRi 30%; PR: 55%) for BCRi-exposed patients (figure 1). After a median follow-up of 315 days the estimated 12-months OS and PFS rate were both 94.8% for BCRi-naïve patients, whereas the estimated 12 months OS and PFS rate for BCRi-exposed patients were 79.1% and 75.7%, respectively, with a median follow-up of 371 days. 79% / 25% of BCRi-naïve and 90% / 44% of BCRi-exposed patients had AEs / SAEs. No new safety signals were observed. Conclusion In this analysis of real-world use of venetoclax in R/R CLL, patients receiving venetoclax in combination with rituximab were predominantly BCRi-naïve. BCRi-exposed patients were more heavily pre-treated, exhibited more genetic high-risk factors, and a higher proportion of patients with comorbidities. Yet, these patients achieved comparable overall response rates. However, complete remissions were more common and the 12 months OS and PFS rates were higher in BCRi-naïve patients. In both groups, VenR treatment was well tolerated. VenR represents a suitable treatment option in BCRi-naïve as well as BCRi-exposed patients. Figure 1 Figure 1. Disclosures Rossi: Gilead: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Verastem: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Cellestia: Honoraria, Research Funding. Hebart: AstraZeneca: Honoraria; Janssen: Honoraria; BMS: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Losem: AbbVie: Honoraria; Amgen: Honoraria. Wolff: Bayer: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Teva: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Schmidt: AbbVie: Current Employment. Famulla: AbbVie: Current Employment. Schmidt: Takeda: Honoraria; Biotest: Honoraria; Alexion: Honoraria; Sanofi-Aventis: Honoraria; Novartis: Honoraria; Incyte: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Noesslinger: Jansen: Honoraria; Roche: Honoraria; Celgene: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria. Schwaner: AbbVie: Honoraria; Amgen: Honoraria; AstraZeneca: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Servier: Honoraria.

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EXPERIENCE WITH DOLUTEGRAVIR IN HIV PATIENTS AT A PUBLIC SECTOR HOSPITAL IN KARACHI, PAKISTAN

Pakistan Armed Forces Medical Journal ◽

10.51253/pafmj.v71i5.6288 ◽

2021 ◽

Vol 71 (5) ◽

pp. 1661-65

Author(s):

Farzana Batool ◽

Sohaima Manzoor ◽

Azizullah Khan Dhiloo ◽

Humera Muhammad Ismail ◽

Shah Muhammad Shaikh ◽

...

Keyword(s):

Viral Load ◽

Control Program ◽

Cross Sectional Study ◽

Virological Suppression ◽

Fixed Dose ◽

Strand Transfer ◽

Good Tolerability ◽

Cross Sectional ◽

Treatment Naïve ◽

Dose Combination

Objective: To study the tolerability and efficacy of dolutegravir in naïve and experienced patients, their management and outcome. Study Design: Cross sectional study. Place and Duration of Study: Ruth KM Pfau Civil Hospital, Karachi Pakistan, from Apr 2018 to Apr 2020. Methodology: In this study all treatment-naïve and experienced HIV infected patients were included and started on integrase strand-transfer inhibitor dolutegravir (DTG) containing fixed dose combination at Sindh AIDS Control Program (SACP) was conducted. We documented virological suppression, defined as a viral load of <1000 copies/ml, immunological and clinical outcomes. Results: Eighty-two patients, of whom 53 (64.6%) were ARV naïve and 29 (35.4%) experienced, were started on DTG. Fifty six (68.3%) were males. The median age was 31.6 ± 9. Of 82, 61 returned for their first follow-up visit for assessment and viral load determination. Of 61, adverse effects to DTG were reported in 12 (19.6%), including 9 with pruritis. Of 35 naive patients, 30 achieved virological suppression by 3.3 ± 0.7 months and 1 at 8 months. All 26 experienced patients achieved virological suppression by 4.5 ± 0.9 months. Overall, of 61 patients, 57 (93.4%) achieved virological suppression, of whom 1 had immunelogical failure and none had clinical failure after 6 months of DTG. Three (3.6%) patients died within the first two months ofinitiating DTG. Conclusion: Dolutegravir has good tolerability, with virological suppression achieved in the majority, including in highly ARV experienced patients.

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The “NOMINAL” trial: Clinical efficacy, cosmetic acceptability, and local tolerability of topical 5% minoxidil lotion without propylene glycol: A 6-month, multicentre, real-life, prospective, assessor-blinded study in 196 subjects with hair loss.

Medical Research Archives ◽

10.18103/mra.v9i6.2515 ◽

2021 ◽

Vol 9 (6) ◽

Author(s):

Laura Alessi ◽

Maria Aloisi ◽

Valentina Amadu ◽

Alex Arena ◽

Ylenia Balice ◽

...

Keyword(s):

Clinical Response ◽

Propylene Glycol ◽

Scale Score ◽

Clinical Efficacy ◽

Real Life ◽

Similar Response ◽

Androgenic Alopecia ◽

Local Tolerability ◽

Good Tolerability ◽

Grade Scale

Background and Trial Objectives: A new propylene glycol (PG)-free 5% minoxidil (Mnx) (PG-Free-Mnx) lotion has been recently commercialized. Clinical efficacy and local tolerability have been, so far, documented in a limited number of patients. The aim of this study was to evaluate the clinical efficacy, cosmetic acceptability, and local tolerability of 6-month application of this new PG-Free Mnx lotion in a real-life situation. Materials and Methods: The NOMINAL (NO-PG MINoxidil reAL life study) trial was performed in 22 out-patients Italian dermatology clinics. A total of 196 subjects of both sexes with a diagnosis of androgenic alopecia (AGA) and female androgenic alopecia (FAGA) were enrolled in the trial, after their written informed consent. PG-Free-Mnx lotion was applied 1 ml twice daily for 6 months. Clinical efficacy was evaluated in an open fashion in all the enrolled subjects with a 5-grade scale score (from-2: severe worsening, to +2: very good improvement in comparison with baseline condition). In a subgroup of subjects (n=60) an assessor-blinded clinical efficacy evaluation has been also performed using high definition standardized and coded scalp global pictures at baseline, and after 6 months by an assessor unaware of the temporal sequence using a 3-grade score (from 0: no improvement to 3: very high improvement). Cosmetic acceptability evaluation was assessed using a 7-item questionnaire using a 10-point scale score, with score 1 meaning not at all and score 10 meaning the worst possible condition. Cosmetic acceptability and clinical efficacy were evaluated after 12 and 24 weeks of treatment. Global tolerability, assessed at week 24, was evaluated with a 4-grade scale score (from -1: very low tolerability to +2: very good tolerability). Results: All but seven (3.6%) subjects concluded the study. Clinical efficacy scores (open evaluation) were 0.8±0.7 and 1.0±0.7 at week 12 and 24, respectively. Good or very good clinical response (score +1 or +2) at week 12 and week 24 was observed in 64% and 74% respectively of the subjects with a similar response in women (75%) and men (73%). Baseline severity of AGA/FAGA was inversely correlated with the clinical response with a better outcome in subjects with AGA type II in comparison with subjects with types III/IV AGA. The clinical efficacy was confirmed by the assessor-blinded evaluation of the subgroup of 60 subjects’ pictures at baseline (clinical score at baseline: 0.2±0.4 vs. 1.8±0.7 after 6 months; p=0.0001; absolute mean difference: 1.6; 95% CI: 1.1 to 2.0). Cosmetic acceptability score mean values were always <2 at each time-point evaluation, demonstrating good or very good acceptability. Global Tolerability score mean±SD value was 1.7±0.4 with 94% of the subjects reporting good or very good tolerability with no differences between men and women. No subjects reported severe or very severe (Tolerability score >7) burning, itching or redness sensations. Conclusions: This new PG-free lotion shows, in real-life conditions, a very good cosmetic acceptability and tolerability profile. Clinical efficacy, evaluated both in open and assessor-blinded fashions, was also documented, and it was in line with the available data of traditional Mnx formulations with propylene glycol.

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Initial safety results of an expanded access program (EAP) of erlotinib in non-small cell lung cancer (NSCLC)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7190 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7190-7190 ◽

Cited By ~ 1

Author(s):

M. Reck ◽

R. Perng ◽

H. Groen ◽

H. Riska ◽

R. Pirker ◽

...

Keyword(s):

Survival Data ◽

Safety Data ◽

Real Life ◽

Predictive Biomarkers ◽

Current Smoker ◽

Common Adverse Event ◽

Phase Iii ◽

Base Line ◽

Open Label ◽

Good Tolerability

7190 Background: Erlotinib is an orally active and selective inhibitor of HER1/EGFR tyrosine kinase. In the BR.21 phase III trial, erlotinib significantly prolonged survival, delayed symptom progression, and improved quality of life in NSCLC patients (pts) (Shepherd et al, NEJM, 2005;353:123). The EAP is an open label, non-randomized, multicentre phase IV trial. Methods: Eligibility criteria included stage III/IV NSCLC pts who failed or were unsuitable for chemotherapy. Pts were given oral erlotinib, 150 mg/d, for as long as treatment provided clinical benefit without unacceptable toxicity. Pts were monitored monthly. Results: In Dec 05, data were available for 1,140 pts from 25 countries, median age 64 y (range 25–91). Key base-line characteristics (% pts) were: males 58%; Caucasian/Oriental 82/15; non-smoker/former or current-smoker 26/73. The % pts with ECOG PS 0/1/2/3 were 20/52/20/8. Most pts (55%) had adenocarcinoma. The % pts receiving erlotinib as 1st/2nd/3rd-line treatment were 12/47/40. As expected, rash was a common adverse event (AE: any grade [gr]: 65%; gr 3/4: 9%). Full safety data were available for 581 pts. Unexpected erlotinib-related AEs were only seen in <2% pts. Erlotinib-related AEs leading to treatment discontinuation were GI disorders in 21 pts (12 pts had gr 3/4 AEs) and skin disorders in 14 pts (6 pts had gr 3/4 rash). Only 10% of pts had dose reductions, mainly due to rash (66%; gr 3 in 8 pts) and diarrhea (17%; gr 3 in 2 pts). The median daily dose of erlotinib was 150mg. Serious erlotinib-related AEs were GI disorders (19 AEs; 11 gr 3/4), mainly diarrhea (8 AEs, 5 were gr 3). Pt accrual and analyses of response, survival data and assessment of various predictive biomarkers are ongoing. Response and survival data will be presented. Conclusions: These interim safety results of erlotinib in the real-life clinical setting in a large number of unselected pts with advanced NSCLC confirm the good tolerability observed in clinical trials. To date, the trial demonstrates that erlotinib is well tolerated, thus, allowing full dose administration to most pts. [Table: see text]

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Therapeutic Options for Homozygous Familial Hypercholesterolemia: The Role of Lomitapide

Current Medicinal Chemistry ◽

10.2174/0929867326666190121120735 ◽

2020 ◽

Vol 27 (23) ◽

pp. 3773-3783

Author(s):

Antonina Giammanco ◽

Angelo B. Cefalù ◽

Davide Noto ◽

Maurizio R. Averna

Keyword(s):

Familial Hypercholesterolemia ◽

Low Density Lipoprotein ◽

Safety Data ◽

Real Life ◽

Density Lipoprotein ◽

Microsomal Triglyceride Transfer Protein ◽

Poor Responders ◽

Homozygous Familial Hypercholesterolemia ◽

Good Tolerability ◽

Apo B

Background: Lomitapide (Juxtapid® in US and Lojuxta® in Europe) is the first developed inhibitor of the Microsomal Triglyceride Transfer Protein (MTP) approved as a novel drug for the management of Homozygous Familial Hypercholesterolemia (HoFH). It acts by binding directly and selectively to MTP thus decreasing the assembly and secretion of the apo-B containing lipoproteins both in the liver and in the intestine. Aims: The present review aims at summarizing the recent knowledge on lomitapide in the management of HoFH. Results: The efficacy and safety of lomitapide have been evaluated in several trials and it has been shown a reduction of the plasma levels of Low-Density Lipoprotein Cholesterol (LDL-C) by an average of more than 50%. Although the most common side effects are gastrointestinal and liver events, lomitapide presents generally with a good tolerability and satisfactory patients compliance. Recently, in Europe, to evaluate the long-term safety and efficacy of lomitapide, the LOWER registry (ClinicalTrials.gov Identifier: NCT02135705) has been established in order to acquire informations on HoFH lomitapidetreated patients from “real life” clinical practice. : Furthermore, the observation that lomitapide decreases triglyceride levels may be considered for patients affected by severe forms of hypertriglyceridemia who undergo recurrent episodes of pancreatitis and are poor responders to conventional treatment. Conclusion: Lomitapide represents an innovative and efficacious drug for the treatment of HoFH. Longterm safety data, treatment of pediatric and pregnant HoFH patients and management of severe hypertriglyceridemia still require further investigations.

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