7 juni 2017:

Ook deze studie: Nivolumab for patients with recurrent glioblastoma progressing on bevacizumab: a retrospective case series gaf geen positief effect op progressievrije tijd noch op overall overleving. Abstract hiervan staat onderaan artikel.

Ook deze studie, gepresenteerd op ASCO 2017: Histopathologic review of suspected disease progression in patients with recurrent glioblastoma (GBM) receiving nivolumab ± ipilimumab: CheckMate 143 is gerelateerd aan de studie die is stopgezet, zie hieronder d.d. 3 mei 2017. Abstract van deze studie staat onderaan artikel.

3 mei 2017: Bron: WFNOS meeting Zürich

Gisteren hadden we een bijeenkomst in het VUmc over ons project: utopie of uitdaging. Daarover later meer. Maar daar hoorde ik dat een fase III studie, de check mate - 143, waarin nivolumab wordt gegeven aan patiënten met een recidief van een hersentumor glioblastoma wordt stopgezet omdat het einddoel, langere ziektevrije tijd niet is gehaald. In deze studie werden patienten in de controlegroep bevacizumab - Avastin als extra behandeling gegeven. Dat al eerder in Europa niet meer wordt gegeven omdat ook dat niet werkte. Echter in Amerika wordt nog altijd bevacizumab naast temodal en/of radiotherapie gegeven en was deze studie ook op ingericht. Andere fase II en III studies waarin nivolumab bv. naast temodal en/of radiotherapie na de eerste diagnose wordt gegeven gaan wel gewoon door.

Er is nog geen studiepublicatie voorhanden omdat het WFNOS congres in Zürich morgen pas van start gaat. Maar de producent Bristol-Myers Squibb gaf al wel een persbericht uit omdat het een beurs genoteerd bedrijf is. Hier het persbericht van Bristol-Myers Squibb. Later zal ik studierapport enz. toevoegen.

Bristol-Myers Squibb Announces Results from CheckMate -143, a Phase 3 Study of Opdivo (nivolumab) in Patients with Glioblastoma Multiforme

Monday, April 3, 2017 10:47 am EDT

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that CheckMate -143, a randomized Phase 3 clinical trial evaluating the efficacy and safety of Opdivo in patients with first recurrence of glioblastoma multiforme (GBM), did not meet its primary endpoint of improved overall survival over bevacizumab monotherapy. These data will be presented on May 7, 2017 at the World Federation of Neuro-Oncology Societies (WFNOS) meeting in Zurich, Switzerland.

“GBM is a historically difficult disease to treat and conventional treatment options have demonstrated limited responses,” said Fouad Namouni, M.D., head of Oncology Development and head of Medical, Bristol-Myers Squibb. “We remain steadfast in our pursuit of treatments for diseases with the highest unmet need and continue our work to determine how our Immuno-Oncology agents can potentially improve outcomes for these patients.”

CheckMate -143 was the first randomized clinical trial in GBM with a PD-1 checkpoint inhibitor. BMS has two first-line GBM clinical trials, CheckMate -498 and CheckMate -548, evaluating the combination of Opdivo with radiation therapy with or without temozolomide in O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated and methylated patients. These trials are moving forward as planned.

histopathologic analyses may help better inform decisions on continuing nivolumab ± ipilimumab in challenging cases, and show that immunotherapies may have intracerebral biological activity.

Histopathologic review of suspected disease progression in patients with recurrent glioblastoma (GBM) receiving nivolumab ± ipilimumab: CheckMate 143.

Sub-category:
Central Nervous System Tumors

Category:
Central Nervous System Tumors

Meeting:
2017 ASCO Annual Meeting

Abstract No:
2001

Citation:
J Clin Oncol 35, 2017 (suppl; abstr 2001)

Author(s): Solmaz Sahebjam, Shakti Ramkissoon, Joachim M. Baehring, Paul James Mulholland, Oliver M. Grauer, Timothy Francis Cloughesy, David A. Reardon, Michael Lim, Ricardo F. Zwirtes, Robert Raymond Latek, Lewis C. Strauss, Keith L. Ligon; H. Lee Moffitt Cancer Canter and Research Institute, Tampa, FL; Foudation Medicine, Inc., Morrisville, NC; Yale School of Medicine, New Haven, CT; University College London Hospitals, London, United Kingdom; Universitätsklinikum Münster, Munster, Germany; University of California, Los Angeles, Los Angeles, CA; Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA; The Johns Hopkins Hospital, Baltimore, MD; Bristol-Myers Squibb, Princeton, NJ

Abstract Disclosures

Abstract:

Background: Patients treated with immunotherapies can have a transient increase in lesion size due to immune cell infiltration that is suggestive of disease progression, but undergo subsequent regression with continued treatment. For patients with GBM, distinguishing progression from immune-related treatment effects using neuroimaging is challenging. Histopathologic examination of tumors could show the activity of immunotherapies in GBM and potentially minimize premature discontinuation of therapy and increase clinical benefit. Neuropathologic data from patients with recurrent GBM treated in CheckMate 143 who underwent biopsy/resection after suspected progression are presented.

Methods: Patients received nivolumab 3 mg/kg (nivo 3) Q2W or nivo 3 + ipilimumab 1 mg/kg (ipi 1) Q3W × 4 doses then nivo 3 Q2W. Tissue collected from patients with suspected radiologic progression was submitted for blinded central review by 2 neuropathologists. Potentially significant treatment effect was defined as ≥30% necrosis/reactive changes and ≤50% viable solid tumor by area in posttreatment samples, or significant morphological changes from a prior biopsy if available. Results were compared with those from automated morphometry, pretreatment biopsy, and control pairs from unrelated patients with GBM treated with standard of care.

Results: Of patients treated with nivo 3 (n = 20) or nivo 3 + ipi 1 (n = 1), 13 had potential treatment-related effects and 8 had no evidence of treatment effects (consistent with disease progression). Results were sent in real time to the treating physician to help inform treatment decisions; 4/13 patients with potential treatment effects continued therapy. Treatment effects were unrelated to age, MGMT methylation status, or PD-L1 expression (clone 28-8; archival tissue). Results were similar for automated morphometry analyses and showed differences between patients receiving nivo ± ipi and unrelated controls.

Conclusions: These results suggest that histopathologic analyses may help better inform decisions on continuing nivo ± ipi in challenging cases, and show that immunotherapies may have intracerebral biological activity. Clinical trial information: NCT02017717

Nivolumab salvage therapy demonstrated no survival advantage in patients with recurrent bevacizumab refractory GBM - Glioblastoma Multiforme emphasizing a continued unmet need in neuro-oncology.

Source: Chamberlain, M.C. & Kim, B.T. J Neurooncol (2017). doi:10.1007/s11060-017-2466-0

Nivolumab for patients with recurrent glioblastoma progressing on bevacizumab: a retrospective case series

Marc C. ChamberlainEmail author
Bryan T. Kim

Marc C. Chamberlain
- 1
Email authorView author's OrcID profile
Bryan T. Kim
- 2

1.Division of Neuro-Oncology, Department of Neurology and Neurosurgery, Fred Hutchinson Cancer Center, Seattle Cancer Care AllianceUniversity of WashingtonSeattleUSA
2.Department of NeurologyUniversity of WashingtonSeattleUSA

Clinical Study

First Online:: 12 May 2017

DOI: 10.1007/s11060-017-2466-0

Cite this article as:: Chamberlain, M.C. & Kim, B.T. J Neurooncol (2017). doi:10.1007/s11060-017-2466-0

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Abstract

A single institution retrospective evaluation of nivolumab following disease progression on bevacizumab in adults with recurrent glioblastoma (GBM) with an objective of determining progression free survival (PFS). There is no accepted therapy for recurrent GBM after failure of bevacizumab. 16 adults, ages 52–72 years (median 62), with recurrent GBM were treated. All patients had previously been treated with surgery, concurrent radiotherapy and temozolomide, and post-radiotherapy temozolomide. Bevacizumab (with or without lomustine) was administered to all patients at first recurrence. Patients were treated with nivolumab only (3 mg/kg) once every 2 weeks at second recurrence. One cycle of nivolumab was defined as 2 treatments. Neurological evaluation was performed bi-weekly and neuroradiographic assessment every 4 weeks. A total of 37 treatment cycles (median 2) were administered of nivolumab in which there were 14 Grade 2 adverse events (AEs) and Grade 3 AEs in two patients. No Grade 4 or 5 AEs were seen. Following 1 month of nivolumab, seven patients demonstrated progressive disease and discontinued therapy. No patient demonstrated a response though nine patients demonstrated neuroradiographic stable response. Survival in the entire cohort ranged from 2 to 6 months with a median of 3.5 months (CI 2.8, 4.2). Median and 6-month PFS at 6 months was 2.0 months (range 1–5 months; CI 1.3, 2.7) and 0% respectively. Nivolumab salvage therapy demonstrated no survival advantage in patients with recurrent bevacizumab refractory GBM emphasizing a continued unmet need in neuro-oncology.

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