Value appraisal of FDA approved cancer drugs over the past decade.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18385-e18385
Author(s):  
Ryan Huey ◽  
Seerat Anand ◽  
Jane Rogers ◽  
Arvind Dasari ◽  
Gauri Rajani Varadhachary ◽  
...  
Keyword(s):  
Health Care ◽  
Adverse Events ◽  
Drug Price ◽  
Progression Free Survival ◽  
New Drugs ◽  
Cancer Drug ◽  
Serious Adverse Events ◽  
Drug Regimens ◽  
Drug Approvals ◽  
Grade 3

e18385 Background: Value based drug pricing is emerging as an imperative health care precept in recognition of the ever-increasing drug costs, especially in oncology. Though novel therapies are regularly approved based on benefit, they are often associated with physical and financial toxicities to patients. We aimed to assess the value of FDA approved oncology drugs defined as their expected clinical benefit compared to their toxicities and costs. Methods: We reviewed all new cancer drug approvals by the FDA from 7/2008-6/2018. Current analysis was restricted to approvals based on overall survival (OS) and progression-free survival (PFS). Data regarding approval indication, effect size, and toxicity were collected from FDA website and publications. Toxicity was estimated as adverse events ≥ grade 3 (or serious adverse events) as reported. Micromedex RED BOOK was used to estimate the total drug price using 2018 average wholesale prices. Price was estimated over 3 months to account for difference in drug regimens. Results: Among the 231 trials used by FDA for approvals in oncology, 115 had OS or PFS as their primary endpoint. Median patients per trial was 539. Of 79 trials with a PFS endpoint, the median HR was 0.50 (range: 0.15 - 0.91); median 3-month drug price was $45,903.72. Compared to the control arm, median toxicity for new drugs was 7% higher (range: -34.4 - 55%). Correlation of HR benefit to 3-month price was 0.06 (95% CI: -0.17 - 0.28, P = 0.61). Correlation of net toxicities to 3-month price was 0.01 (95% CI: -0.25 - 0.26, P = 0.94). Of 43 trials with an OS endpoint, the median HR was 0.72 (range: 0.37 - 0.94); median 3-month price was $43,523.46. Relative to control arm, median toxicity for new drugs was 4% higher (range: -34.4 - 45.8%). Correlation of HR benefit to 3-month price was 0.38 (95% CI: 0.08 - 0.62, P = 0.012). Correlation of net toxicities to 3-month price was -0.12 (95% CI: -0.45 - 0.24, P = 0.50). Conclusions: Drug approvals in oncology come with a high cost and drug prices have very little correlation with estimated benefit in outcomes and toxicities. As policies evolve to promote higher value in health care, attention should be paid to benefits of drugs in relation to pricing and using biomarker-based patient selection to maximize benefits and minimize toxicities.

Value appraisal of FDA approved cancer drugs over the past decade.

2019 ◽  
Vol 37 (27_suppl) ◽  
pp. 115-115
Author(s):  
Ryan Huey ◽  
Seerat Anand ◽  
Jane Elizabeth Rogers ◽  
Arvind Dasari ◽  
Gauri Rajani Varadhachary ◽  
...  
Keyword(s):  
Health Care ◽  
Adverse Events ◽  
Drug Price ◽  
Progression Free Survival ◽  
New Drugs ◽  
Cancer Drug ◽  
Serious Adverse Events ◽  
Drug Regimens ◽  
Drug Approvals ◽  
Grade 3

115 Background: Value based drug pricing is emerging as an imperative health care precept in recognition of the ever-increasing drug costs, especially in oncology. Though novel therapies are regularly approved based on benefit, they are often associated with physical and financial toxicities to patients. We aimed to assess the value of FDA approved oncology drugs defined as their expected clinical benefit compared to their toxicities and costs. Methods: We reviewed all new cancer drug approvals by the FDA from 7/2008-6/2018. Current analysis was restricted to approvals based on overall survival (OS) and progression-free survival (PFS). Data regarding approval indication, effect size, and toxicity were collected from FDA website and publications. Toxicity was estimated as adverse events ≥ grade 3 (or serious adverse events) as reported. Micromedex RED BOOK was used to estimate the total drug price using 2018 average wholesale prices. Price was estimated over 3 months to account for difference in drug regimens. Results: Among the 231 trials used by FDA for approvals in oncology, 115 had OS or PFS as their primary endpoint. Median patients per trial was 539. Of 79 trials with a PFS endpoint, the median HR was 0.50 (range: 0.15 - 0.91); median 3-month drug price was $45,903.72. Compared to the control arm, median toxicity for new drugs was 7% higher (range: -34.4 - 55%). Correlation of HR benefit to 3-month price was 0.06 (95% CI: -0.17 - 0.28, P = 0.61). Correlation of net toxicities to 3-month price was 0.01 (95% CI: -0.25 - 0.26, P = 0.94). Of 43 trials with an OS endpoint, the median HR was 0.72 (range: 0.37 - 0.94); median 3-month price was $43,523.46. Relative to control arm, median toxicity for new drugs was 4% higher (range: -34.4 - 45.8%). Correlation of HR benefit to 3-month price was 0.38 (95% CI: 0.08 - 0.62, P = 0.012). Correlation of net toxicities to 3-month price was -0.12 (95% CI: -0.45 - 0.24, P = 0.50). Conclusions: Drug approvals in oncology come with a high cost and drug prices have very little correlation with estimated benefit in outcomes and toxicities. As policies evolve to promote higher value in health care, attention should be paid to benefits of drugs in relation to pricing and using biomarker-based patient selection to maximize benefits and minimize toxicities.

Trabectedin for recurrent WHO grade II or III meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2007-2007 ◽  
Author(s):  
Matthias Preusser ◽  
Antonio Silvani ◽  
Emilie Le Rhun ◽  
Riccardo Soffietti ◽  
Giuseppe Lombardi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Somatostatin Analogue ◽  
Synthesis Methods ◽  
Serious Adverse Events ◽  
Who Grade ◽  
Sea Squirt ◽  
Grade Ii ◽  
Grade 3

2007 Background: EORTC-1320-BTG investigated the activity, safety and quality of life of therapy with the tetrahydroisoquinoline alkaloid trabectedin (Yondelis) in patients with recurrent higher-grade meningiomas. Trabectedin was originally derived from the Caribbean sea squirt, Ecteinascidia turbinata, and currently is manufactured by total synthesis. Methods: Adult patients with histological diagnosis of WHO grade II or III meningioma and radiologically documented progression after maximal feasible surgery and radiotherapy were randomly assigned in a 2:1 ratio to receive intravenous trabectedin (1.5 mg/m2every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Results: Within 22.1 months, we randomized a total of 90 patients (n=29 in LOC arm, n=61 in trabectedin arm) in 35 institutions and nine countries. In the LOC arm, the following treatments were administered: hydroxyurea (n=11), bevacizumab (n=9), none (n=4), chemotherapy (n=3), somatostatin analogue (n=1), combined chemotherapy and somatostatin analogue (n=1). With 71 PFS events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] for progression, 1.42; 80% CI, 1.00-2.03; p=0.204) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) in the LOC and 21.1% (95% CI, 11.3%-32.9%) in the trabectedin arm. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR for death, 0.98; 95% CI, 0.54-1.76; p=0.94).Grade 3 to 5 adverse events occurred in 44.4% (18.5% related, 4 serious adverse events, 0 lethal events) of the patients in the LOC and 59% (32.8% related, 57 serious adverse events and 2 toxic deaths) of patient in the trabectedin arm. Conclusions: In this first prospective randomized trial performed in recurrent grade II or III meningioma, trabectedin did not improve PFS and OS and was associated with significantly higher toxicity as compared to LOC treatment. The data collected in this study may serve as benchmark for future clinical trials in this setting. Clinical trial information: NCT02234050.

scholarly journals PL3.2 Trabectedin for recurrent WHO grade II or III meningioma: a randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG)

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii2-iii3 ◽  
Author(s):  
M Preusser ◽  
A Silvani ◽  
E Le Rhun ◽  
R Soffietti ◽  
G Lombardi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Somatostatin Analogue ◽  
Serious Adverse Events ◽  
Who Grade ◽  
Sea Squirt ◽  
Tumor Group ◽  
Grade Ii ◽  
Grade 3

Abstract BACKGROUND EORTC-1320-BTG investigated the activity, safety and quality of life of therapy with the tetrahydroisoquinoline alkaloid trabectedin (Yondelis®) in patients with recurrent higher-grade meningiomas. Trabectedin was originally derived from the Caribbean sea squirt, Ecteinascidia turbinata, and currently is manufactured by total synthesis. METHODS Adult patients with histological diagnosis of WHO grade II or III meningioma and radiologically documented progression after maximal feasible surgery and radiotherapy were randomly assigned in a 2:1 ratio to receive intravenous trabectedin (1.5 mg/m2every three weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). RESULTS Within 22.1 months, we randomized a total of 90 patients (n=29 in LOC arm, n=61 in trabectedin arm) in 35 institutions and nine countries. In the LOC arm, the following treatments were administered: hydroxyurea (n=11), bevacizumab (n=9), none (n=4), chemotherapy (n=3), somatostatin analogue (n=1), combined chemotherapy and somatostatin analogue (n=1). With 71 PFS events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] for progression, 1.42; 80% CI, 1.00–2.03; p=0.204) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) in the LOC and 21.1% (95% CI, 11.3%-32.9%) in the trabectedin arm. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR for death, 0.98; 95% CI, 0.54–1.76; p=0.94).Grade 3 to 5 adverse events occurred in 44.4% (18.5% related, 4 serious adverse events, 0 lethal events) of the patients in the LOC and 59% (32.8% related, 57 serious adverse events and 2 toxic deaths) of patient in the trabectedin arm. CONCLUSIONS In this first prospective randomized trial performed in recurrent grade II or III meningioma, trabectedin did not improve PFS and OS and was associated with significantly higher toxicity as compared to LOC treatment. The data collected in this study may serve as benchmark for future clinical trials in this setting.

A phase II study of patupilone in patients (pts) with metastatic castration- resistant prostate cancer (CRPC) who have progressed after docetaxel

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5139-5139 ◽  
Author(s):  
E. K. Beardsley ◽  
F. Saad ◽  
B. Eigl ◽  
P. Venner ◽  
S. Hotte ◽  
...  
Keyword(s):  
Adverse Events ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Serious Adverse Events ◽  
Disease Response ◽  
Measurable Disease ◽  
Psa Response ◽  
Grade 3 ◽  
Ecog Ps

5139 Background: Chemotherapy for pts with CRPC who have progressed after docetaxel remains to be defined. Patupilone is an epothilone with broad spectrum pre-clinical activity including in taxane resistant models. Methods: Multicenter, 2-stage design. Pts with metastatic CRPC with progressive disease during or within 6 months of receiving docetaxel were eligible. Patupilone was initially given 10mg/m 2 IV every 3 weeks. PSA response rate (≥50% decline) was the primary endpoint (H0 = 15%, H1 = 25%, α = 0.1, β = 0.2). Secondary endpoints were measurable disease response, serial pain and analgesics scores, progression free survival (PFS) and overall survival (OS). Results: 83 pts were enrolled from March 2007-June 2008. 401 cycles administered (median 5, range 1–15). Baseline characteristics (range): median age 67 (47–85), PSA 212 (2.6–11520), hemoglobin 118 (89–160), median time to progression after docetaxel 1.0 months (0.0–6.0), number of prior chemotherapy regimens 1:2:3+ in 45:28:10 pts, ECOG PS 0–1:2 in 73:10 pts, disease in bone/lymph nodes/viscera in 76/47/14 pts respectively. In the first 6 pts, gastrointestinal serious adverse events (AE) occurred in 4 pts (diarrhea and vomiting) which lead to a dose reduction of patupilone to 8 mg/m2 for subsequent patients. Grade 3/4 related adverse events at this dose included fatigue (16%), diarrhea (13%) and anorexia (5%). There were no grade 3/4 hematologic AEs. In 78 pts evaluable for PSA response, PSA declines of ≥30% and ≥50% have occurred in 44/78 (56%) and 35/78 (45%) with a confirmed PSA response in 25 pts (32%). Partial response occurred in 5% and stable disease in 64% of 44 evaluable pts. Pain response (2 point decline on 6 point scale) occurred in 36 (51%) of 71 pts eligible for analysis. Median PFS for PSA and non-PSA outcomes (measurable disease/symptomatic progression or death) was 7.6 months (3.7–11.5) and 5.6 months (3.9–7.3) respectively. Follow up for OS is continuing. Conclusions: Patupilone 8 mg/m2 every 3 weeks was well tolerated and associated with encouraging PFS, PSA and pain responses in pts with docetaxel resistant/refractory disease. Further investigation of patupilone in this population is warranted. [Table: see text]

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

scholarly journals Safety and Efficacy of Four Drug Versus Three Drug Regimens Among Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Saad Ullah Malik ◽  
Nazma Hanif ◽  
Priyanka Kumari ◽  
Khadija Noor Sami ◽  
Chase Warner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Standard Of Care ◽  
Drug Regimen ◽  
P Value ◽  
Newly Diagnosed ◽  
Drug Regimens ◽  
Grade 3

Introduction: During recent years there has been a boom in the availability of treatments for multiple myeloma (MM). Based on the status of disease (newly diagnosed or relapsed/refractory), several regimens have successfully improved progression free survival (PFS) and overall survival (OS) in these two types of patients. Triple drug regimen is considered the current standard of care for newly diagnosed MM patients. However, with the advent of four drug regimens, some studies demonstrated a significant improvement in PFS and OS compared to standard of care where as others showed marginal to no difference. Also, it remains unclear whether the benefits of using four drug regimen outweigh the risks. Thus, the aim of our meta-analysis was to compare the efficacy and safety of four drug versus three drug regimens among newly diagnosed multiple myeloma patients. Methods: We built a PICO based search strategy using keywords like "multiple myeloma", "randomized clinical trials" and ran literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov ranging from the date of inception till 16th July, 2020. A pre-validated data extraction sheet was used to extract data on PFS, OS and ≥Grade 3 hematologic adverse events at the longest follow-up. We included only randomized clinical trials (RCTs) comparing four versus three drug regimen in newly diagnosed MM patients. We excluded studies other than RCTs, studies conducted on relapsed refractory MM patients or other plasma cell dyscrasias. A generic variance weighted random effects model (DerSimonian and Laird) was used to derive hazard ratio estimates along with their 95% confidence intervals (CIs) for PFS and OS. Risk ratio along with its 95% CIs was estimated for Grade ≥3 hematologic adverse events. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2 test (I2 &gt;50% was consistent with a high degree of heterogeneity). A pre-specified sensitivity analysis was also performed for risk of adverse events. Cochrane Collaboration's tool was used to assess the quality of included RCTs and GRADE was used to rate the quality of evidence. Results: Initial search retrieved 7622 titles. After duplicate removal, 4880 articles were left. Following initial screening, 58 articles were considered for full text review. Of these only 3 studies (n=2277) met inclusion criteria. Four drug regimens included daratumumab, bortezomib, melphalan-prednisone (D-VMP), daratumumab, bortezomib, thalidomide-dexamethasone (D-VTd) and bortezomib and melphalan prednisone and thalidomide (VMPT-VT) respectively. Whereas, three drug regimens were bortezomib, melphalan-prednisone (VMP), bortezomib, thalidomide-dexamethasone (VTd) and bortezomib, melphalan and prednisone (VMP) respectively. There was a significant improvement in PFS when 4 vs 3 drug regimens were compared in patients with newly diagnosed MM (HR: 0.53, 95% CI: 0.46-0.62, p-value:&lt;0.001, I2: 0%). Also, OS improved significantly in four drug regimen group (HR: 0.62, 95% CI: 0.51-0.76, p-value:&lt;0.001, I2: 3.5%). There was no statistically significant difference in any grade ≥3 hematologic adverse events when 4 vs 3 drug regimens were compared (RR: 1.26, 95% CI: 0.93-1.73, p-value:0.14, I2: 93%). Sensitivity analysis after removing D-VTd regimen from any grade ≥3 hematologic adverse events revealed similar results (RR: 1.05, 95% CI: 0.97-1.13, p-value:0.23, I2: 23%) confirming the robustness of analysis. When each hematologic adverse event was looked at separately, there was no difference between 4 vs 3 drug regimen in rates of anemia (RR: 0.99, 95% CI: 0.76-1.28, p-value:0.92, I2: 0%), neutropenia (RR: 1.39, 95% CI: 1.00-1.94, p-value:0.05, I2: 85%) and thrombocytopenia (RR: 1.13, 95% CI: 0.92-1.39, p-value:0.24, I2: 33%). There was low risk of bias and strength of evidence was of moderate. Conclusion: Using four drug regimens, compared to three drug regimens, significantly improves PFS and OS among newly diagnosed multiple myeloma patients without any difference in the risk of ≥3 grade hematologic adverse events. Further randomized clinical trials are required to establish four drug regimen as standard of care for patients with newly diagnosed multiple myeloma. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Efficacy and Safety of PEGPH20 in Pancreatic Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 17 ◽  
Author(s):  
Vinod Solipuram ◽  
Harish Gopalakrishna ◽  
Gayatri Naira ◽  
Akhila Mohan
Keyword(s):  
Pancreatic Cancer ◽  
Placebo Group ◽  
Febrile Neutropenia ◽  
Adverse Events ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Thromboembolic Events ◽  
Serious Adverse Events ◽  
Significant Difference

Introduction: Pancreatic cancer is an aggressive tumor that had an estimated 57,600 new cases and 47,050 deaths in 2020 in the US alone. Recent studies have targeted tumor microenvironment (TME) for better delivery of systemic chemotherapy like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles was identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR=0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), however, there was statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there is an increased incidence of serious adverse events with the use of PEGPH20 compared to standard therapies.

Retrospective Review of Safety and Efficacy of Anlotinib in Advanced Osteosarcoma With Metastases After Failure of Standard Multimodal Therapy

2021 ◽  
Author(s):  
Hanqing Li ◽  
Yang Li ◽  
Lei Song ◽  
Qiuchi Ai ◽  
shuai zhang
Keyword(s):  
Adverse Events ◽  
Multimodal Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Common Drug ◽  
Grade 3 ◽  
Therapeutic Doses

Abstract To study and observe the safety and efficacy of anlotinib in the treatment of advanced osteosarcoma with metastases. We retrospectively studied patients with advanced osteosarcoma and metastases who received anlotinib treatment in our hospital from June 2018 to April 2020. All patients had received standard multimodal therapies, before taking anlotinib. Therapeutic doses of anlotinib were 12 mg for adults and 10 mg for children and adolescents once a day for 2 consecutive weeks, followed by a week of withdrawal. This 3-week cycle of treatment was continued until the tumor progressed rapidly or the patients failed to tolerate the side effects. Adverse drug reactions were recorded, and therapeutic efficacy was evaluated based on progression free survival (PFS), disease control rate (DCR), overall survival (OS), and objective response rate (ORR). The median PFS was 9.81 ± 0.9 months, and the 6-month and 10-month PFS rates were 73.3% and 33.3%, respectively. The median OS was 11.43 ± 0.58 months. No patients achieved complete response. After 6 months of treatment, the DCR and ORR were 80% and 13.3%, respectively. No drug-related deaths or Grade 4 adverse events occurred in the patients. Five patients (33.3%) had Grade 3 adverse events. The most common drug-related adverse events were hand-food syndrome, fatigue, high blood pressure, anorexia, and pneumothorax. Anlotinib had a certain curative effect on patients with advanced osteosarcoma and metastases after failure of standard treatment. The adverse events were mostly tolerable or relieved after treatment.

Biweekly Raltitrexed in Combination with Irinotecan (RIR) as Second-Line Therapy for Patients with Metastatic Colorectal Cancer: A Non-Randomized, Open-Label Phase II Trial.

2020 ◽  
Author(s):  
Ke Cheng ◽  
Yu-Wen Zhou ◽  
Ye Chen ◽  
Zhi-Ping Li ◽  
Meng Qiu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Overall Response Rate ◽  
Progression Free Survival ◽  
Second Line ◽  
Open Label ◽  
Second Line Therapy ◽  
Free Survival ◽  
Common Grade ◽  
Open Label Phase ◽  
Grade 3

Abstract Background Irinotecan-based doublet chemotherapy strategy was standard second-line backbone treatment for patients with oxaliplatin‑refractory metastatic colorectal cancer(mCRC). The aim of this study was to evaluate tolerability and efficacy of raltitrexed combined with irinotecan biweekly administered as the second-line therapy for mCRC patients.Methods The study was a single-center, non-randomized, open-label phase II trial. Patients with mCRC after failure with first-line treatment of oxaliplatin and fluoropyrimidine or its derivatives were enrolled. Irinotecan (180 mg/m2) and raltitrexed (2.5 mg/m2) were given intravenously on day 1. Cycles were repeated every 2 weeks. The primary endpoint was progression-free survival, and the secondary endpoints included overall response rate, disease control rate, overall survival and treatment related adverse events. Results Between December 2012 and October 2016, 35 patients were enrolled. 33 and 35 patients were assessed for response and safety, respectively. The overall response rate (ORR) was 8.6 %, and the disease control rate (DCR) was 71.4%. The median progression-free survival (PFS) was 4.5 months (95% CI 3.8–5.2). The median overall survival was 12.0 months (95% CI 8.5–15.5). Four patients received conversion therapy to no evidence of disease (NED), and 2 patients were still alive with beyond 24 months survival. The most common grade 3/4 hematological adverse events were leukopenia (8.6%), neutropenia (5.7%). The most common grade 3/4 nonhematological adverse events were anorexia (14.3%), vomiting (14.3%), nausea (11.4%) and fatigue (8.6%). Two patients discontinued the protocol treatment because of treatment-related gastrointestinal adverse events. No one died from treatment-related events. The incidence and severity of toxicity was irrelevant to UGT1A1 status.Conclusions The combination of irinotecan with raltitrexed is an active, convenient and acceptable toxic regimen for second-line treatment for mCRC patients, which needs further study as a chemotherapy backbone to be combined with targeted agents in mCRC.Trial registration No. ChiCTR-ONC-12002767. The study was registered with the Chinese Clinical Trial Registry at 29 Octorber 2012, http://www.chictr.org.cn/index.aspx.

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