Time course of regorafenib-associated adverse events in the phase III CORRECT study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 467-467 ◽  
Author(s):  
Axel Grothey ◽  
Eric Van Cutsem ◽  
Alberto F. Sobrero ◽  
Salvatore Siena ◽  
Alfredo Falcone ◽  
...  
Keyword(s):  
Overall Survival ◽  
Placebo Group ◽  
Adverse Events ◽  
Survival Benefit ◽  
Time Course ◽  
Dose Intensity ◽  
Phase Iii ◽  
Multikinase Inhibitor ◽  
Study Results ◽  
Overall Survival Benefit

467 Background: Regorafenib (REG) is an oral multikinase inhibitor that has recently demonstrated significant overall survival benefit vs placebo in the randomized phase III CORRECT study. We examined the time course of adverse events (AEs) in the CORRECT study. Methods: Regorafenib (REG) is an oral multikinase inhibitor that has recently demonstrated significant overall survival benefit vs placebo in the randomized phase III CORRECT study. We examined the time course of adverse events (AEs) in the CORRECT study. Results: The safety population comprised 753 patients (pts): REG n=500; placebo n=253. The mean treatment duration was 12.1 ± 9.7 weeks in the REG group and 7.8 ± 5.2 weeks in the placebo group. Treatment-emergent AEs occurred at any grade in 99.6% of REG pts and 96.8% of placebo pts, at grade 1/2 in 21.6% and 47.8%, respectively, at grade 3 in 56.0% and 26.5%, respectively, and at grade 4/5 in 22.0% and 22.5%, respectively. AEs occurring in ≥10% more REG than placebo pts were fatigue, hand–foot skin reaction (HFSR), anorexia, diarrhea, weight loss, voice changes, hypertension, rash/desquamation, oral mucositis, fever, hyperbilirubinemia, low platelet count. The most frequent AEs deemed to be regorafenib related were HFSR, fatigue, diarrhea, hypertension, and rash/desquamation. The frequency of these AEs over time is shown in the Table. The incidence of HFSR, fatigue, hypertension, and rash/desquamation peaked in cycle 1 and tapered to a relatively stable lower incidence over later cycles. The incidence of diarrhea remained relatively constant throughout treatment. AEs led to dose modification in 66.6% of pts in the REG group and 22.5% in the placebo group. Data on dose intensity across treatment cycles will be presented. Conclusions: In the CORRECT trial, the incidences of the most common AEs in the REG group peaked early during treatment. There appeared to be no evidence for cumulative toxicity of REG. Clinical trial information: NCT01103323. [Table: see text]

A Review of Targeted Therapies in the Management of Advanced-stage Hepatocellular Carcinoma

2011 ◽  
Vol 07 (04) ◽  
pp. 234
Author(s):  
Tony Hung ◽  
Richard S Finn ◽  
◽  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Targeted Therapies ◽  
Survival Benefit ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Multikinase Inhibitor ◽  
Early Hcc ◽  
Overall Survival Benefit ◽  
Study Designs

Hepatocellular carcinoma (HCC) ranks third as a leading cause of cancer death worldwide and has steadily increased in incidence. Due to the asymptomatic nature of early HCC, most patients unfortunately present with advanced or unresectable tumour. While traditional cytotoxic agents have failed to demonstrate a clear survival benefit, the development of newer, molecular targeted therapies has shown promising results in the management of HCC. Notably, sorafenib, an oral multikinase inhibitor, has proven its efficacy in two randomised phase III studies and is currently the only approved systemic therapy in HCC. While the overall survival benefit for patients on sorafenib is modest, it has highlighted the unmet medical need of patients with advanced HCC. Currently, there are several agents in development as both first-line and second-line therapies. Critical to their successful development will be the study designs and the selection of patients most likely to benefit taking into account the complex interplay between underlying liver disease/cirrhosis, cancer and outcomes. The recent failure of sunitinib, a promising oral multikinase inhibitor, because of a greater incidence of adverse events and failure to extend overall survival emphasises these points. This review highlights and summarises the evidence and ongoing challenges in the development of new molecular targeted therapy in HCC.

Correlation between efficacy and toxicity in pts with pretreated advanced melanoma treated within the Italian cohort of the ipilimumab expanded access programme (EAP).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9065-9065 ◽  
Author(s):  
Anna Maria Di Giacomo ◽  
Antonio M Grimaldi ◽  
Paolo Antonio Ascierto ◽  
Paola Queirolo ◽  
Michele Del Vecchio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Therapeutic Option ◽  
Stage Iv ◽  
Phase Iii ◽  
Expanded Access Programme ◽  
Fast Progression ◽  
Phase Iii Trials ◽  
Access Programme ◽  
Overall Survival Benefit

9065 Background: Ipilimumab was the first agent approved for the treatment of unresectable or metastatic melanoma that showed an overall survival benefit in randomised phase III trials. Early clinical studies explored the potential relationship between immune-related adverse events (irAEs) associated with ipilimumab and antitumor activity but no definitive conclusion has been reached. Here, we evaluated the possible correlation between efficacy of ipilimumab treatment and irAEs in patients (pts) enrolled in the EAP in Italy. Methods: Ipilimumab was available upon physician request for pts aged ≥16 years with unresectable stage III/stage IV melanoma who had either failed systemic therapy or were intolerant to ≥1 systemic treatment and for whom no other therapeutic option was available. Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for 4 doses. Tumour assessments were conducted at baseline and after completion of induction therapy using immune-related response criteria. Pts were monitored for adverse events (AEs), including immune-related AEs (irAEs), using Common Terminology Criteria for Adverse Events v.3.0. Results: In total, 855 Italian pts participated in the EAP from June 2010 to April 2012 across 55 centres. Among 833 evaluable pts, 278 pts (33.4%) reported an irAE and 555 (66.6%) did not. As of December 2012, the disease control rates among pts with or without irAEs were 35.3% and 33.9% respectively. We noted that there was a difference in the distribution of pts with or without irAEs among pts who experienced a fast progression, thus not being able to receive at least 3 cycles, and pts with slow progression. In fact, due to the mechanism of action of the drug and consequent delayed onset of irAEs, pts with irAEs among fast and slow progressors were 22% and 37% respectively. Therefore, median overall survival was evaluated by adjusting the 2 groups for this factor and results showed a comparable survival between pts who reported an irAE and pts who did not (10.0 vs 9.7 months respectively). Conclusions: This exploratory analysis of EAP data suggest that activity and efficacy of ipilimumab is not related with the occurrence of irAEs.

Time course of regorafenib-associated adverse events in the phase III CORRECT study

2013 ◽  
Vol 51 (08) ◽  
Author(s):  
C Denzlinger ◽  
A Grothey ◽  
AF Sobrero ◽  
E van Cutsem ◽  
S Siena ◽  
...  
Keyword(s):  
Adverse Events ◽  
Time Course ◽  
Phase Iii

Randomized Trial of Adjuvant Chemotherapy With Mitomycin, Fluorouracil, and Cytosine Arabinoside Followed by Oral Fluorouracil in Serosa-Negative Gastric Cancer: Japan Clinical Oncology Group 9206–1

2003 ◽  
Vol 21 (12) ◽  
pp. 2282-2287 ◽  
Author(s):  
Atsushi Nashimoto ◽  
Toshifusa Nakajima ◽  
Hiroshi Furukawa ◽  
Masatsugu Kitamura ◽  
Taira Kinoshita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Survival Benefit ◽  
Curative Resection ◽  
Cancer Recurrence ◽  
Phase Iii ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Significant Difference

Purpose: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients (excluding patients who were T1N0), we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated. Patients and Methods: From January 1993 to December 1994, 252 patients were enrolled into the study and allocated randomly to adjuvant chemotherapy or surgery alone. The chemotherapy comprised intravenous mitomycin 1.33 mg/m2, fluorouracil (FU) 166.7 mg/m2, and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery, and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2. The primary end point was relapse-free survival. Overall survival and the site of recurrence were secondary end points. Results: Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection. There were no treatment-related deaths and few serious adverse events. There was no significant difference in relapse-free and overall survival between the arms (5-year relapse-free survival 88.8% chemotherapy v 83.7% surgery alone; P = .14 and 5-year survival 91.2% chemotherapy v 86.1% surgery alone; P = .13, respectively). Nine patients (7.1%) in the chemotherapy arm and 17 patients (13.8%) in the surgery-alone arm had cancer recurrence. Conclusion: There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection, and there was no statistical difference between the two arms relating to the types of cancer recurrence. We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice.

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