Treatment of Genotype 1 HCV Treatment-Naïve Patients: final results of phase III study ADVANCE

Cabozantinib is an oral tyrosine kinase inhibitor that targets VEGFR, MET and the TAM (TYRO3, AXL, MER) family of kinase receptors. In addition to their role in tumor growth and angiogenesis, cabozantinib targets promote an immune-suppressive microenvironment. Cabozantinib is approved as single-agent therapy for patients with advanced hepatocellular carcinoma who received prior sorafenib. Owing to its antitumor and immunomodulatory properties, cabozantinib is being developed in combination with immune checkpoint inhibitors. Early studies of these combinations have shown promising antitumor activity and tolerability in patients with solid tumors. Here, we describe the rationale and design of COSMIC-312, a Phase III study evaluating the safety and efficacy of cabozantinib in combination with atezolizumab (anti–PD-L1 monoclonal antibody) versus sorafenib for treatment-naive patients with advanced hepatocellular carcinoma. ClinicalTrial.gov Registration: NCT03755791

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Telaprevir in Combination with Peginterferon and Ribavirin In Genotype 1 HCV Treatment-Naïve Patients, Prior Relapsers and Prior Non-Responders: Pooled Analysis Of PROVE1, PROVE2, PROVE3 and Study 107

The American Journal of Gastroenterology ◽

10.14309/00000434-201010001-00274 ◽

2010 ◽

Vol 105 ◽

pp. S102

Author(s):

Mitchell Shiffman ◽

Thomas Berg ◽

Andrew Muir ◽

John McHutchison ◽

Jean-Michel Pawlotsky ◽

...

Keyword(s):

Pooled Analysis ◽

Genotype 1 ◽

Hcv Treatment ◽

Treatment Naïve ◽

Peginterferon And Ribavirin

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A single-arm, open-label, U.S. expanded access study of vemurafenib in patients with metastatic melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8567 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 8567-8567

Author(s):

Lynn Mara Schuchter ◽

Lawrence E. Flaherty ◽

Omid Hamid ◽

Gerald P. Linette ◽

Sigrun Hallmeyer ◽

...

Keyword(s):

Metastatic Melanoma ◽

Response Rate ◽

Phase Iii ◽

Open Label ◽

Expanded Access ◽

Treatment Naïve ◽

Phase Iii Study ◽

Prior Systemic Therapy ◽

Ecog Ps

8567 Background: Vemurafenib (vem) has been FDA approved for the treatment of unresectable or metastatic BRAFV600E mutated melanoma since August 2011 based on results of a randomized phase III study (treatment-naive) and a single arm phase II study (previously treated). We report results of an expanded access study that allowed appropriate patients (pts) to receive vem until the drug was approved. Methods: Eligible pts had metastatic melanoma with a BRAFV600E mutation as detected by the cobas 4800 BRAFV600 Mutation Test. Enrolled pts received oral vem 960 mg b.i.d. Adverse events (AEs) were evaluated for vem-related toxicities; tumor responses were assessed using RECIST 1.1. Results: 29 US sites screened 745 pts and enrolled 374 from December 2010 until October 2011. The following results are based on a median follow up time and treatment duration of 2 months. At baseline, mean age of pts was 54 y with 22% of pts ≥65 y; 75% had stage M1c disease; 29% had received radiotherapy for brain metastases. 19% of pts were ECOG PS 2 or 3; 71% of pts had prior systemic therapy for metastatic melanoma (21% 1 regimen; 50% ≥2 regimens). 50 pts had prior adjuvant treatment. At data cut-off, 243 pts had sufficient follow-up time for tumor assessment. In this group, the unconfirmed overall response rate was 52% (95% CI, 46 to 59). The median time to response was 1.8 months. Based on 240 pts with available ECOG PS status at time of analysis, response rate was 53% for pts with ECOG PS 0 or 1 (n=209), and 45% for pts with ECOG PS 2 or 3 (n=31). 370 pts were evaluable for safety analysis. The most common vem-related AEs were rash (36%), arthralgia (33%) and fatigue (21%) with the majority (~90%) of grade 1 or 2. 25 vem-related serious AEs were reported in 5.4% of pts with a slightly higher rate of pts with ECOG PS 2 or 3 (8.7%) compared to ECOG PS 0 or 1 (4.7%). 18% of pts missed at least one dose and 11% of pts required dose reduction of at least one level due to AEs. Conclusions: This expanded access study, with its limited follow-up time, confirms the established rapid and high tumor response rate with vem. No new safety signals were detected. Compared to the overall population, pts with an ECOG PS 2 or 3 demonstrated a similar benefit.

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The efficacy and safety of sunitinib in patients with advanced well-differentiated pancreatic neuroendocrine tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.380 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 380-380 ◽

Cited By ~ 3

Author(s):

Eric Raymond ◽

Matthew H. Kulke ◽

Shukui Qin ◽

Michael Schenker ◽

Antonio Cubillo ◽

...

Keyword(s):

Clinical Trial ◽

Neuroendocrine Tumors ◽

Phase Iii ◽

Pancreatic Neuroendocrine Tumors ◽

Pivotal Phase ◽

Treatment Naïve ◽

Phase Iii Study ◽

Previously Treated Patients ◽

Previously Treated ◽

Well Differentiated

380 Background: Sunitinib was approved by the FDA in 2011 for treatment of progressive, well-differentiated, advanced pancreatic neuroendocrine tumors (pNETs) based on a pivotal phase III study (NCT00428597) that showed a significant increase in progression-free survival (PFS) over placebo following early study termination. Subsequently, the FDA requested a post-approval study to support these findings. Methods: In this open-label, phase IV clinical trial (NCT01525550), patients with progressive, well-differentiated, unresectable advanced/metastatic pNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study. Primary endpoint was investigator-assessed PFS per RECIST 1.0. This study is ongoing. Results: Sixty one treatment-naïve and 45 previously treated patients with progressive pNETs were treated with sunitinib: mean age, 54.6 years; males, 59.4%; white, 63.2%; ECOG PS 0, 65.1% or PS 1, 34.0%; and prior somatostatin analog, 48.1% (treatment-naïve, 39.3%; previously treated, 60.0%). At the data cutoff date, 82 (77%) patients discontinued treatment, mainly due to disease progression (46%). Median duration of treatment was ~11.9 months. Investigator-assessed median PFS (mPFS) was 13.2 months (95% CI, 10.9–16.7) in the overall population, with comparable mPFS in treatment-naïve and previously treated patients (13.2 vs 13.0 months). mPFS per independent radiologic review was 11.1 months (95% CI, 7.4–16.6). Objective response rate (ORR) per RECIST was 24.5%: 21.3% in treatment-naïve and 28.9% in previously treated patients. Median overall survival, although not yet mature, was 37.8 months. Treatment-emergent, all-causality adverse events (AEs) reported by ≥ 20% of all patients included neutropenia, diarrhea, leukopenia, fatigue, hand–foot syndrome, hypertension, abdominal pain, dysgeusia, and nausea. Most common grade 3/4 AEs were neutropenia (22%) and diarrhea (9%). Conclusions: The mPFS of 13.2 months and ORR of 24.5% observed in this study support the outcomes of the pivotal phase III study of sunitinib in pNETs and confirm its activity in this setting. AEs were consistent with known safety profile of sunitinib. Clinical trial information: NCT01525550.

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