Efficacies of anlotinib monotherapy versus gemcitabine-based chemotherapy for patients with advanced soft tissue sarcoma after the failure of anthracycline-based chemotherapy.

OBJECTIVE: The purpose of this study was to compare the antitumor efficacy of anlotinib with gemcitabine-based chemotherapy as subsequent treatment regimens in patients with advanced non-specific soft tissue sarcoma (STS) after the failure of anthracycline-based chemotherapy. METHODS: Patients diagnosed with advanced STS who were treated with either anlotinib or gemcitabine-based chemotherapy between May 2009 and May 2023 in our center were eligible. All patients experienced disease progression or recurrence after the anthracycline-based chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were disease control rate (DCR), overall survival (OS) and safety. RESULTS: We included 49 patients receiving anlotinib and 45 patients receiving gemcitabine-based chemotherapy. The median follow-up time was 76.9 weeks (range 2.9-678.9 weeks). The DCR (65.3% vs. 57.8%; p = 0.610), PFS (24.0 weeks vs. 18.6 weeks; p = 0.669) and OS (79.4 weeks vs. 87.0 weeks; p = 0.471) of anlotinib and gemcitabine-based chemotherapy indicated similar clinical efficacy. Moreover, exploratory subgroup analyses showed that patients with STS originating from limbs and trunk were inclined to benefit from anlotinib treatment (median PFS: 31.3 weeks vs. 12.4 weeks; p = 0.045). ECOG PS was an independent predictor of the PFS [Hazard Ratio (HR) 0.31; 95% confidence interval (CI) 0.11-0.85; p = 0.023] and OS (HR 0.26, 95%CI 0.10-0.70; p = 0.008) in the anlotinib group. While neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic factor of the PFS (HR 0.33, 95%CI 0.11-0.98; p = 0.045) in the gemcitabine-based chemotherapy group. The incidence of grade 3 or higher related AEs in anlotinib and gemcitabine-based chemotherapy was 20.4% (n = 10) and 20.0% (n = 9), respectively. CONCLUSION: Our research suggested that anlotinib and gemcitabine-based chemotherapy showed similar clinical efficacy and safety in the subsequent treatment of advanced STS after the failure of anthracycline-based chemotherapy.

Safety and efficacy of Rucaparib in the treatment of ovarian cancer and patients with BRCA mutation: a systematic review and meta-analysis of phase III randomized clinical trials.

INTRODUCTION: Our systematic review and meta-analysis aimed to evaluate the clinical efficacy and safety of Rucaparib, a PARP inhibitor (PARPi), in patients with ovarian cancer and BRCA mutation. METHODS: Online databases were comprehensively searched for all phase III Randomized trials that used Rucaparib therapy for ovarian cancer patients and patients having BRCA mutation. Efficacy results are progression-free survival and overall response rate in addition to addressing its safety concerns. RESULTS: After pooling data from 4 clinical trials, the analysis showed a significant improvement in PFS among ovarian cancer patients and for the maintenance therapy with a hazard ratio (HR) of 0.49 (95% CI 0.34-0.73, p = 0.0003) and 0.42 (95% CI 0.29-0.62, p < 0.0001), respectively. For patients with BRCA mutations, the PFS showed significant improvement with a (HR) of 0.42 (95% CI 0.25-0.71, p < 0.001). A difference was observed in the risk of grade ≥ 3 TEAEs between the two groups (RR = 2.48; 95% CI 1.40-4.37). CONCLUSION: Rucaparib demonstrated significant efficacy in improving PFS and ORR in ovarian cancer patients, particularly those having BRCA mutations. However, they should be closely monitored due to the greater risk of various adverse effects.

Phase Ib study of anlotinib in combination with anti-PD-L1 antibody (TQB2450) in patients with advanced acral melanoma.

BACKGROUND: Acral melanoma, the most common subtype of melanoma in Asians, is often diagnosed at an advanced stage and responds poorly to current programmed cell death protein 1 (PD-1) inhibitors. OBJECTIVES: To evaluate the safety and efficacy of TQB2450 and anlotinib in patients with advanced acral melanoma in a phase Ib study (NCT03991975). METHODS: Patients received TQB2450 (1200 mg every 3 weeks) and anlotinib (10 mg or 12 mg once daily, 2-week on/1-week off) in the dose-escalation and dose-expansion phases. The primary endpoints were dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and objective response rate (ORR). RESULTS: Nineteen patients were enrolled between June 2019 and June 2022. The majority of patients (16 of 19 patients) received anlotinib and TQB2450 as first-line treatment. No DLTs were observed, and MTD was not reached. Eighteen (94.7%) out of 19 patients experienced treatment-related adverse events (TRAEs), but most were grade 1 or 2. Grade 3 or greater TRAEs occurred in seven patients (36.8%). The ORR was 26.3% (two complete responses and three partial responses). The disease control rate was 73.7%. The median duration of response was 30.3 months [95% confidence interval (CI): 5.8-NA]. The median progression-free survival (PFS) was 5.5 months (95% CI: 2.8-NA), and median overall survival was 20.3 months (95% CI: 14.8-NA). Whole-exome sequencing suggested that acquired drug resistance might be attributed to activation of the MAPK signalling pathway and transformation to an immunosuppressive tumour environment. CONCLUSIONS: TQB2450 combined with anlotinib showed favourable tolerance and promising anti-tumour activity with a prolonged PFS compared with anti-PD1 monotherapy in patients with advanced acral melanoma.

Real life data on nintedanib safety: idiopathic pulmonary fibrosis versus systemic sclerosis-interstitial lung disease and strategies adopted to manage adverse effects.

OBJECTIVE: Nintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects. METHODS: Patients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them. RESULTS: Twenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months-p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months-p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN. CONCLUSION: We presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects.

A real-world disproportionality analysis of Rucaparib: Post-marketing Pharmacovigilance Data.

BACKGROUND: Rucaparib has been approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. However, the long-term safety of rucaparib in large sample population was unknown. The presented study aimed to evaluate rucaparib-associated adverse events (AEs) according to the real-world pharmacovigilance database. METHODS: Disproportionality analysis was conducted to assess the association between rucaparib and its AEs. Data were collected from the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS) between January 2017 and June 2022. The characteristics of rucaparib-related AEs, and the onset time were further analyzed. RESULTS: A total of 9,296,694 AE reports were recorded in the FAERS during the study period, among which 7,087 reports were associated with rucaparib. About 135 rucaparib-related AE signals in 15 system organ class (SOCs) were identified. The most common AEs included anaemia, thrombocytopenia, nausea, vomiting, fatigue, blood creatinine increase, alanine aminotransferase increase, and aspartate aminotransferase increase, which were listed in the label for rucaparib. Of note, 21 new and unexpected significant AEs that off-label were also found in our study, such as preferred term (PTs) of intestinal obstruction, gastrooesophageal reflux disease, blood iron decreased, dehydration, and hypersomnia. The median onset time of rucaparib-related AEs was 12 days (interquartile range [IQR] 1-62 days), and had early failure types. CONCLUSION: Our study demonstrated potential new AEs of rucaparib, and further studies were expected to confirm the results.

Cebranopadol for the Treatment of Chronic Pain.

PURPOSE OF REVIEW: Regardless of the etiology, if pain persists chronically, it can detrimentally impact multiple aspects of a patient's well-being. Both physical and psychological effects are significant in many chronic pain patients. In this regard, psychological consequences can alter a patient's quality of life, functionality, and social functioning. Opioids have been the long-established gold standard for acute pain treatment in settings such as the postoperative period. An alternative to opioids in pain management has been highly sought after. Through a non-selective mechanism, cebranopadol is a first-in-class oral drug which combines agonism of the mu and nociceptin opioid peptide (NOP) receptors to provide improved analgesia, while reducing the occurrence of many typically opioid side effects. This manuscript is a narrative review of the possible use of cebranopadol in pain management. RECENT FINDINGS: In pre-clinical studies, cebranopadol was similar to morphine in its pain control efficacy. In a phase IIa trial, cebranopadol was superior to placebo in reducing pain. In a randomized clinical trial, cebranopadol was superior to morphine. Another study concluded that cebranopadol had a lower misuse potential when compared to hydromorphone. In summary, cebranopadol offers new opportunities in treating chronic moderate to severe pain, while also countering risks of addiction. Additional studies are warranted to further evaluate the safety and efficacy of cebranopadol. In this regard, cebranopadol could prove to be a promising alternative to current pain treatment options.

Effect of umifenovir (arbidol) versus standard care on clinical outcome in patients with COVID-19: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to spread quickly throughout the world, mainly due to the lack of effective drug therapies and vaccines. The effectiveness of the antiviral drug umifenovir needs to be further clarified. METHODS: This retrospective cohort study included 1254 patients who were diagnosed with COVID-19 between February 19 and April 5, 2020 in Hubei Maternity and Child Health Hospital. They were divided into umifenovir group (n = 760, 60.60%) and control group (n = 496) without using umifenovir. The primary endpoint was a composite of intubation or death in a time-to-event analysis. The clinical outcomes were compared between the two groups using multivariable Cox analysis with inverse probability weighting according to the propensity score. RESULTS: A total of 760 (60.60%) patients received umifenovir, and 496 patients did not do so. Of the enrolled patients, 1049 (83.65%) had mild or moderate COVID-19, and the remaining 205 had severe or critical COVID-19. The mortality rate in the umifenovir group was 2.76% (21/760) versus 2.02% (10/494) in the control group. In terms of treatment outcomes, the discharge status of the patients in the umifenovir group was no better than that in the control group after propensity score matching (n = 485 in each group). In addition, the respiratory rate, a severe condition, or critical condition of the disease were the three main risk factors affecting the endpoint of death (p = 0.0028, p = 0.0009 and p < 0.0001, respectively). CONCLUSION: This retrospective cohort study showed that oral administration of umifenovir alone did not improve outcomes for patients with COVID-19.

Efficacy and Safety of Anlotinib in Overall and Disease-Specific Advanced Gynecological Cancer: A Real-World Study.

Purpose: Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer have not been comprehensively evaluated. We conducted this study to address this issue in the real-world setting. Patients and Methods: Data from patients treated with Anlotinib for persistent, recurrent or metastatic gynecological cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1-14 every 3 weeks until disease progression, severe toxicity occurred, or death. In this study, disease-specific advanced gynecological cancer was mainly referred to cervical, endometrial, and ovarian cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: A total of 249 patients were analyzed, with a median follow-up of 14.5 months. The overall ORR and DCR were 28.1% [95% confidence interval (CI) 22.6% to 34.1%] and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of Anlotinib (>700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to Anlotinib treatment was pain/arthralgia (18.3%). Conclusion: In conclusion, Anlotinib holds promise in treating patients with advanced gynecological cancer including its disease-specific types, with reasonable efficacy and tolerable safety.

Phase 1/2a clinical trial in ALS with ropinirole, a drug candidate identified by iPSC drug discovery.

iPSC-based drug discovery led to a phase 1/2a trial of ropinirole in ALS. 20 participants with sporadic ALS received ropinirole or placebo for 24 weeks in the double-blind period to evaluate safety, tolerability, and therapeutic effects. Adverse events were similar in both groups. During the double-blind period, muscle strength and daily activity were maintained, but a decline in the ALSFRS-R, which assesses the functional status of ALS patients, was not different from that in the placebo group. However, in the open-label extension period, the ropinirole group showed significant suppression of ALSFRS-R decline and an additional 27.9 weeks of disease-progression-free survival. iPSC-derived motor neurons from participants showed dopamine D2 receptor expression and a potential involvement of the SREBP2-cholesterol pathway in therapeutic effects. Lipid peroxide represents a clinical surrogate marker to assess disease progression and drug efficacy. Limitations include small sample sizes and high attrition rates in the open-label extension period, requiring further validation.

Risk of Malnutrition in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease Treated With Nintedanib in the Randomized, Placebo-Controlled SENSCIS Trial.

OBJECTIVE: To assess adverse events (AEs) in relation to baseline body mass index (BMI) and the risk of malnutrition in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) treated with nintedanib. METHODS: Among patients with SSc-ILD randomized to receive nintedanib or placebo in the SENSCIS trial, we assessed AEs in subgroups by baseline BMI ≤20 kg/m2 and BMI >20 kg/m2 , and the risk of malnutrition using a modified version of the Malnutrition Universal Screening Tool (MUST), over 52 weeks. RESULTS: The AE profile of nintedanib was similar between subgroups with a baseline BMI ≤20 kg/m2 (n = 61) and a baseline BMI >20 kg/m2 (n = 515). In these subgroups, respectively, AEs led to treatment discontinuation in 16.7% and 15.9% of the nintedanib group and 13.5% and 8.0% of the placebo group, respectively. Based on the modified MUST, the proportions of patients who had a low risk of malnutrition at baseline and at their last assessment were 74.0% in the nintedanib group and 78.1% in the placebo group, while the proportions who were classified as at low risk at baseline but at high risk by their last assessment were 4.5% in the nintedanib group and 1.0% in the placebo group. CONCLUSION: In the SENSCIS trial, most patients with SSc-ILD remained at low risk of malnutrition over 52 weeks, but the proportion at high risk was higher in patients who received treatment with nintedanib compared to those who received placebo. Management of disease manifestations and AEs that may be associated with weight loss is important to reduce the risk of malnutrition in patients with SSc-ILD.

Pan-cancer efficacy and safety of anlotinib plus PD-1 inhibitor in refractory solid tumor: A single-arm, open-label, phase II trial.

The combination of immunotherapy and antiangiogenic agents for the treatment of refractory solid tumor has not been well investigated. Thus, our study aimed to evaluate the efficacy and safety of a new regimen of anlotinib plus PD-1 inhibitor to treat refractory solid tumor. APICAL-RST is an investigator-initiated, open-label, single-arm, phase II trial in patients with heavily treated, refractory, metastatic solid tumor. Eligible patients experienced disease progression during prior therapy without further effective regimen. All patients received anlotinib and PD-1 inhibitor. The primary endpoints were objective response and disease control rates. The secondary endpoints included the ratio of progression-free survival 2 (PFS2)/PFS1, overall survival (OS) and safety. Forty-one patients were recruited in our study; 9 patients achieved a confirmed partial response and 21 patients had stable disease. Objective response rate and disease control rate were 22.0% and 73.2% in the intention-to-treat cohort, and 24.3% and 81.1% in the efficacy-evaluable cohort, respectively. A total of 63.4% (95% confidence interval [CI]: 46.9%-77.4%) of the patients (26/41) presented PFS2/PFS1 >1.3. The median OS was 16.8 months (range: 8.23-24.4), and the 12- and 36-month OS rates were 62.8% and 28.9%, respectively. No significant association was observed between concomitant mutation and efficacy. Thirty-one (75.6%) patients experienced at least one treatment-related adverse event. The most common adverse events were hypothyroidism, hand-foot syndrome and malaise. This phase II trial showed that anlotinib plus PD-1 inhibitor exhibits favorable efficacy and tolerability in patients with refractory solid tumor.

Drug-Induced Thrombocytopenia Due to Nintedanib during Treatment of Idiopathic Pulmonary Fibrosis.

Nintedanib is a tyrosine kinase inhibitor that was approved for the treatment of patients with idiopathic pulmonary fibrosis in 2014. The most common side effect of Nintedanib is diarrhea, and thrombocytopenia is a rare side effect of Nintedanib. The exact mechanism is unknown, and the literature lacks case reports of this phenomenon. Here, we report the case of a patient who developed thrombocytopenia 12 weeks after starting treatment with Nintedanib. The patient underwent an extensive work up for infectious, hematological, autoimmune, and neoplastic diseases. The patient's thrombocytopenia resolved following cessation of Nintedanib. This case is significant as it reports a rare side effect that might have detrimental consequences if not recognized and treated timely. Additionally, the onset of thrombocytopenia was delayed, 3 months after the initiation of Nintedanib. We also highlight the various literature regarding drug-induced thrombocytopenia and explore the necessary work-up needed to exclude other potential diagnoses. We hope to advocate for multidisciplinary teams to be aware of patients with pulmonary fibrosis on Nintedanib so that this adverse effect can be recognized promptly.

Anlotinib succeeded in rescue therapy for hyperprogression induced by immune checkpoint inhibitors: a case report.

Immune checkpoint inhibitors are important therapeutic agents for advanced non-small-cell lung cancer. Nevertheless, these new therapies can lead to unexpected serious complications, such as hyperprogressive disease (HPD). Once HPD occurs, most patients die within 1-3 months due to the lack of effective treatments. This paper reports a patient with advanced lung cancer who experienced HPD after two cycles of third-line sintilimab treatment. Sintilimab was stopped, and rescue anlotinib treatment was started. A partial response was achieved, and the clinical signs and symptoms were relieved. The patient died 7 months later from a lung infection. Although the mechanisms are unknown, anlotinib might be effective in managing non-small-cell lung cancer with HPD after sintilimab.

Immune checkpoint inhibitors (ICIs) are important drugs against advanced lung cancer, but these new drugs can lead to some unexpected serious complications, such as an uncontrolled progression of the disease (termed hyperprogressive disease [HPD]). Once HPD occurs, most patients die within 1­3 months because of the lack of effective treatments for HPD. This article presents a patient with advanced lung cancer who experienced HPD during treatment with an ICI. The ICI treatment was stopped, and anlotinib, another drug against cancer, was started. A partial response was achieved, and the symptoms were relieved. The patient died 7 months later from a lung infection but not of his lung cancer.

Surufatinib-induced renal thrombotic microangiopathy: first case report and review of literature.

Angiogenesis inhibitors such as tyrosine kinase inhibitors (TKIs) are common therapeutics currently used to treat oncologic disease. Surufatinib is a novel, small-molecule multiple receptor TKI approved by the National Medical Products Administration (NMPA) for the treatment of progressive, advanced, and well-differentiated pancreatic and extrapancreatic neuroendocrine tumours (NETs). Thrombotic microangiopathy (TMA) is a well-documented complication of TKIs targeting the VEGF-A/VEGFR2 signalling pathway. Here, we describe a 43-year-old female patient with biopsy-proven TMA and nephrotic syndrome due to surufatinib treatment for adenoid cystic carcinoma. Histological lesions included glomerular endothelial swelling, widening of subendothelial spaces, mesangiolysis, and double contour, which caused nephrotic proteinuria. Effective management was achieved by drug withdrawal and oral anti-hypertensive regents. The management of surufatinib-related nephrotoxicity without compromising its anticancer effects is challenging. Hypertension and proteinuria must be closely monitored during drug use to reduce or stop the dose in a timely manner before severe nephrotoxicity occurs.

Outcomes with panobinostat in heavily pretreated multiple myeloma patients.

Panobinostat is an oral pan histone-deacetylase inhibitor used in the treatment of relapsed and refractory multiple myeloma. Previously published studies of panobinostat demonstrated synergy with bortezomib but included few patients exposed to newer agent combinations (ie, panobinostat plus daratumumab or carfilzomib). Here, we report outcomes of panobinostat-based combinations at an academic medical center among patients whose disease had been heavily pretreated with modern agents. We retrospectively analyzed 105 patients with myeloma treated with panobinostat at The Mount Sinai Hospital in New York City between October 2012 and October 2021. These patients had a median age of 65 (range 37-87) and had received a median of 6 prior lines of therapy while in 53% the disease was classified as triple class refractory and in 54% the disease had high-risk cytogenetics. Panobinostat was most commonly utilized at 20 mg (64.8%) as part of a triplet (61.0%) or quadruplet (30.5%). Aside from steroids, panobinostat was most commonly administered in combination with lenalidomide, pomalidomide, carfilzomib, and daratumumab in descending order of frequency. Among the 101 response-evaluable patients, the overall response rate was 24.8%, clinical benefit rate (≥minimal response) was 36.6%, and median progression-free survival was 3.4 months. Median overall survival was 19.1 months. The most common toxicities ≥grade 3 were hematologic, primarily neutropenia (34.3%), thrombocytopenia (27.6%), and anemia (19.1%). Panobinostat-based combinations produced modest response rates in patients with heavily pretreated multiple myeloma, over half of whom had triple-class refractory disease. Panobinostat warrants continued investigation as a tolerable oral option for recapturing responses in patients whose disease has progressed after receipt of standard-of-care therapies.

A Narrative Review of Real-World Data on the Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis.

Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF) and other progressive fibrosing interstitial lung diseases. Placebo-controlled trials showed that the adverse event profile of nintedanib was characterised mainly by gastrointestinal events, particularly diarrhoea. We review the data from all published real-world studies of the safety of nintedanib in patients with IPF. These real-world data were consistent with the safety profile observed in clinical trials and described in the product label. The most common adverse events were diarrhoea, nausea and vomiting, but these infrequently led to permanent treatment discontinuation. Liver enzyme elevations were observed, supporting the recommendation for regular monitoring of liver enzymes, particularly in the first few months of treatment. Bleeding and cardiovascular adverse events were rarely reported. As in clinical trials, in real-world studies, reductions of the nintedanib dose, treatment interruptions and use of anti-diarrhoeal medications were frequently employed to manage adverse events. Few data are available on the use of nintedanib in patients who are elderly or have advanced disease, but there are some data to suggest a greater rate of treatment discontinuation in these patients. Effective management of adverse events associated with nintedanib is important to minimise their impact.

Sunitinib therapy for imatinib-resistant and/or intolerant gastrointestinal stromal tumors: comparison of safety and efficacy between standard and reduced dosage regimens.

BACKGROUND: Sunitinib therapy for patients with imatinib-resistant and/or intolerant gastrointestinal stromal tumors (GISTs) often causes severe adverse events (AEs) that lead to treatment discontinuation. METHODS: We retrospectively reviewed the clinical records of imatinib-resistant and/or intolerant GIST patients who underwent sunitinib therapy in our institutions between 2007 and 2020. Forty-one patients were enrolled and divided into two groups on the basis of the starting dosage: the standard dosage group (50 mg/day, 21 patients) and the reduced dosage group (37.5 mg/day, 20 patients). Tolerability, safety and clinical efficacy of the two groups were compared. RESULTS: Three patients (14%) in the standard dosage group and another three (15%) in the reduced dosage group (P = 1.000) discontinued sunitinib therapy because of AEs. The incidences of grade 3 or more severe treatment-related AEs were 90 and 75%, respectively (P = 0.238). Two possible treatment-related deaths were noted in the standard dosage group. Clinical efficacy was comparable between the two groups: median time to treatment failure and overall survival were 4.5 months [interquartile range (IQR), 3.6-9.0] and 13.7 months (IQR, 7.5-22.9) in the standard dosage group and 4.6 months (IQR, 2.7-17.0) and 13.4 months (IQR, 9.3-36.8) in the reduced dosage group, respectively. CONCLUSIONS: The reduced dosage of 37.5 mg sunitinib tended to decrease toxicity and the incidences of severe AEs and treatment-related deaths. This reduced dosage regimen showed equivalent clinical efficacy including patient survival. The reduced dosage of 37.5 mg sunitinib can be adopted as an alternative therapy for patients with imatinib-resistant and/or intolerant GISTs.

Nintedanib in Asian patients with progressive fibrosing interstitial lung diseases: Results from the INBUILD trial.

BACKGROUND AND OBJECTIVE: In the INBUILD trial in patients with progressive fibrosing interstitial lung diseases (ILDs), nintedanib reduced the rate of decline in forced vital capacity (FVC) with an adverse event profile characterized mainly by gastrointestinal events. We analysed the effects of nintedanib in the subset of Asian subjects. METHODS: Subjects with fibrosing ILDs other than idiopathic pulmonary fibrosis who had shown progression of ILD at any time within the prior 24 months despite management deemed appropriate in clinical practice were randomized to receive nintedanib or placebo. We analysed the rate of decline in FVC (ml/year) over 52 weeks in all Asian subjects and in Asian subjects with a usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT). RESULTS: One hundred sixty-four subjects in the INBUILD trial were of Asian race. The rate of decline in FVC (ml/year) over 52 weeks in this subgroup was -116.8 in the nintedanib group and -207.9 in the placebo group (difference: 91.0 [95% CI: 8.1, 173.9]; nominal p = 0.03). In Asian subjects with a UIP-like fibrotic pattern on HRCT, the rate of decline in FVC (ml/year) over 52 weeks was -130.1 in the nintedanib group and -224.2 in the placebo group (difference: 94.1 [5.5, 182.7]; nominal p = 0.04). Adverse events led to treatment discontinuation in 19.0% of the nintedanib group and 13.8% of the placebo group. CONCLUSION: In Asian patients with progressive fibrosing ILDs, nintedanib reduced the rate of decline in FVC with adverse events that were manageable for most patients.