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Sunitinib for atypical and anaplastic meningioma
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WHO grade II (atypical) and grade III (anaplastic) meningiomas recur in a high proportion of patients (50–80%) and are often refractory to both surgery and radiotherapy, responding poorly to medical therapy. A prospective, multicentre singlearm phase 2 trial investigated the efficacy of sunitinib, a tyrosine kinase inhibitor that inhibits VEGF and PDGF receptors, which are over-expressed in meningiomas. 36 patients with WHO grade II and III recurrent or progressive meningiomas were enrolled. They were heavily pre-treated (median five recurrences) and received sunitinib at 50 mg per day for days 1–28 of a 42-day cycle. An additional exploratory group of six patients included haemangiopericytoma, recurrent WHO grade I meningioma and haemangioblastoma. Disease response assessment was done by MRI.
The primary endpoint of the study, progression-free survival at 6 months, was 42%, with secondary endpoints median progression-free survival of 5·2 months (95% CI 2·8–8·3) and median overall survival of 24·6 months (16·5–38·4). Correlation studies were also done with MR perfusion and immunohistochemistry. Adverse events included four (8%) intratumoural haemorrhages, of which one was fatal, one (2%) grade 4 thrombotic microangiopathy, and one (2%) grade 3 gastrointestinal perforation. MRI perfusion in the exploratory group indicated that sunitinib is an active agent. Expression of VEGFR2 predicted progression-free survival of a median of 1·4 months in VEGFR2-negative patients versus 6·4 months in VEGFR2positive patients (p=0·005). The authors advocate proceeding with a randomised trial.
Belddyn Jones (Gray Institute for Radiation Oncology and Biology, Oxford, UK) commented, “As in many studies using tyrosine kinase inhibiting agents, modest tumour growth restraint and reduced tumour blood flow have been identified, but at the expense of considerable toxicity. The use of such agents may be far more effective if scheduled after surgery or radiotherapy in patients at high risk of recurrence.” Susan Short (Institute of Cancer and Pathology, Leeds, UK) added, “This is the first study to show that a molecular targeting agent can be effective [in this setting]. Tantalisingly, they do suggest that that we may be able to identify tissue-based biomarkers to predict for response, which would be enormously valuable.”
Cavallini James/Bsip/Science Photo Library
Sunitinib for atypical and anaplastic meningioma
Published Online August 15, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)70384-5 For the study by Kaley and colleagues see Neuro-Oncology 2014; published online Aug 6. DOI:10.1093/ neuonc/nou148
Ahmadur Rahman
PSA testing beneficial for prostate cancer Results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up have confirmed a substantial reduction in prostate cancer mortality attributable to testing of prostate-specific antigen (PSA), with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. ERSPC was a multicentre randomised trial that assessed PSA testing in eight European countries. It was based on a predefined centralised database, analysis plan, and core age group (55–69 years) of population. Previously, ERSPC showed that screening could yield significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up; but despite those results, prostate cancer screening remained controversial because of adverse effects such as overdiagnosis, which often led to overtreatment with subsequent side-effects.
In this update, Fritz Schröder and coworkers reported results of mortality from prostate cancer with followup to 2010, with analyses truncated at 9 years, 11 years, and 13 years of follow-up. From population registries, the researchers identified eligible men aged 50–74 years, who were randomly assigned to screening (intervention group) or no intervention (control group). 7408 cases in the intervention group and 6107 cases of the control group had data truncated at 13 years of follow-up. Between the intervention and control groups, the rate ratios of prostate cancer incidence were 1·91 (95% CI 1·83–1·99) after 9 years, 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratios of prostate cancer mortality were 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) after 13 years.
www.thelancet.com/oncology Vol 15 September 2014
According to the researchers, the absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for the screening. Schröder (Erasmus University Medical Center, Rotterdam, Netherlands) commented, “We’re backing the use of our data in individual decision taking and recommend the use of validated decision aids which are currently available”. Laurent Azoulay (Jewish General Hospital, Montreal, Canada) said, “Prostate cancer screening is a controversial issue, but perhaps some new analyses can provide some insights on whether or not it should be performed systematically.”
Published Online August 15, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)70385-7 For the ERSPC study see Lancet 2014; published online Aug 7. http://dx.doi. org/10.1016/S01406736(14)60525-0
Sanjeet Bagcchi e424
WHO grade II (atypical) and grade III (anaplastic) meningiomas recur in a high proportion of patients (50–80%) and are often refractory to both surgery and radiotherapy, responding poorly to medical therapy. A prospective, multicentre singlearm phase 2 trial investigated the efficacy of sunitinib, a tyrosine kinase inhibitor that inhibits VEGF and PDGF receptors, which are over-expressed in meningiomas. 36 patients with WHO grade II and III recurrent or progressive meningiomas were enrolled. They were heavily pre-treated (median five recurrences) and received sunitinib at 50 mg per day for days 1–28 of a 42-day cycle. An additional exploratory group of six patients included haemangiopericytoma, recurrent WHO grade I meningioma and haemangioblastoma. Disease response assessment was done by MRI.
The primary endpoint of the study, progression-free survival at 6 months, was 42%, with secondary endpoints median progression-free survival of 5·2 months (95% CI 2·8–8·3) and median overall survival of 24·6 months (16·5–38·4). Correlation studies were also done with MR perfusion and immunohistochemistry. Adverse events included four (8%) intratumoural haemorrhages, of which one was fatal, one (2%) grade 4 thrombotic microangiopathy, and one (2%) grade 3 gastrointestinal perforation. MRI perfusion in the exploratory group indicated that sunitinib is an active agent. Expression of VEGFR2 predicted progression-free survival of a median of 1·4 months in VEGFR2-negative patients versus 6·4 months in VEGFR2positive patients (p=0·005). The authors advocate proceeding with a randomised trial.
Belddyn Jones (Gray Institute for Radiation Oncology and Biology, Oxford, UK) commented, “As in many studies using tyrosine kinase inhibiting agents, modest tumour growth restraint and reduced tumour blood flow have been identified, but at the expense of considerable toxicity. The use of such agents may be far more effective if scheduled after surgery or radiotherapy in patients at high risk of recurrence.” Susan Short (Institute of Cancer and Pathology, Leeds, UK) added, “This is the first study to show that a molecular targeting agent can be effective [in this setting]. Tantalisingly, they do suggest that that we may be able to identify tissue-based biomarkers to predict for response, which would be enormously valuable.”
Cavallini James/Bsip/Science Photo Library
Sunitinib for atypical and anaplastic meningioma
Published Online August 15, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)70384-5 For the study by Kaley and colleagues see Neuro-Oncology 2014; published online Aug 6. DOI:10.1093/ neuonc/nou148
Ahmadur Rahman
PSA testing beneficial for prostate cancer Results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up have confirmed a substantial reduction in prostate cancer mortality attributable to testing of prostate-specific antigen (PSA), with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. ERSPC was a multicentre randomised trial that assessed PSA testing in eight European countries. It was based on a predefined centralised database, analysis plan, and core age group (55–69 years) of population. Previously, ERSPC showed that screening could yield significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up; but despite those results, prostate cancer screening remained controversial because of adverse effects such as overdiagnosis, which often led to overtreatment with subsequent side-effects.
In this update, Fritz Schröder and coworkers reported results of mortality from prostate cancer with followup to 2010, with analyses truncated at 9 years, 11 years, and 13 years of follow-up. From population registries, the researchers identified eligible men aged 50–74 years, who were randomly assigned to screening (intervention group) or no intervention (control group). 7408 cases in the intervention group and 6107 cases of the control group had data truncated at 13 years of follow-up. Between the intervention and control groups, the rate ratios of prostate cancer incidence were 1·91 (95% CI 1·83–1·99) after 9 years, 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratios of prostate cancer mortality were 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) after 13 years.
www.thelancet.com/oncology Vol 15 September 2014
According to the researchers, the absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for the screening. Schröder (Erasmus University Medical Center, Rotterdam, Netherlands) commented, “We’re backing the use of our data in individual decision taking and recommend the use of validated decision aids which are currently available”. Laurent Azoulay (Jewish General Hospital, Montreal, Canada) said, “Prostate cancer screening is a controversial issue, but perhaps some new analyses can provide some insights on whether or not it should be performed systematically.”
Published Online August 15, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)70385-7 For the ERSPC study see Lancet 2014; published online Aug 7. http://dx.doi. org/10.1016/S01406736(14)60525-0
Sanjeet Bagcchi e424