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Prescription Cancer Drugs
KCA: Hypertension May Predict Response in RCC (CME/CE)
Posted by: admin in Prescription Cancer Drugs on August 16th, 2010
- Explain to interested patients that development of hypertension may predict whether metastatic kidney cancer responds to treatment with a targeted agent.
- Explain that the findings were based on a retrospective review of a database, not a prospective study.
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
CHICAGO — Transient hypertension correlated with improved survival in patients with metastatic renal cell carcinoma who were treated with sunitinib (Sutent), investigators found.
Patients who had a maximum systolic blood pressure of 140 mm Hg or greater had almost a fourfold increase in overall survival compared with those who had lower maximum systolic pressure, Brian Rini, MD, of the Cleveland Clinic, reported here at the International Kidney Cancer Symposium.
A maximum diastolic blood pressure of 90 mm Hg or greater was associated with a doubling of overall survival, he said.
A hypertensive spike in blood pressure had a similar association with response rate and progression-free survival.
“In this retrospective exploratory analysis of metastatic renal cell carcinoma patients treated with sunitinib, transient hypertension was associated with improved clinical outcome, supporting the hypothesis that hypertension is a viable biomarker of antitumor efficacy in this patient population,” Rini said.
The data revealed no clear risk of hypertension-associated complications in sunitinib-treated patients, and use of antihypertensive medication did not affect the targeted agent’s antitumor efficacy, he added.
Hypertension is a common side effect of treatment with angiogenesis inhibitors that target vascular endothelial growth factor (VEGF). Some investigators have suggested that transient hypertension is a marker of clinical response.
Treatment with sunitinib has been associated with a 30% incidence of hypertension, including 10% grade 3. The effect has not been associated with changes in cardiac structure or function, Rini said.
A retrospective analysis of patients with a variety of tumor types showed an association between elevated diastolic blood pressure and clinical outcome with the VEGF inhibitor axitinib, particularly in patients with metastatic renal cell carcinoma (J Clin Oncol 2006; 24: 16-24).
Continuing the exploration of hypertension and response to anti-VEGF therapy, Rini and colleagues retrospectively analyzed pooled data for 544 patients with metastatic renal cell carcinoma treated with first-line or second-line sunitinib. Antitumor efficacy consisted of progression-free survival, overall survival, and objective response rate.
Investigators increased the safety analysis to include an additional 4,000 patients with metastatic renal cell carcinoma from an expanded-access study.
Hypertension was defined by the maximum and the mean blood pressure (systolic and diastolic).
Of the 544 patients in the efficacy analysis, 81% had systolic hypertension (≥140 mm Hg) at some point after the first day of the first cycle of sunitinib therapy, and 67% had diastolic hypertension (≥90 mm Hg).
Hypertensive patients had a median blood pressure of 160/98 mm Hg compared with 130/82 mm Hg in patients who did not have hypertension during treatment with sunitinib.
The efficacy analysis showed that patients with a maximum systolic pressure ≥140 mm Hg had a median overall survival of 30.5 months compared with 7.8 months in patients without systolic hypertension (P<0.0001).
With respect to diastolic pressure, a maximum pressure ≥90 mm Hg was associated with a median overall survival of 32.1 months compared with 15 months in patients who did not have hypertension (P<0.0001).
Median progression-free survival was 12.5 months and 13.4 months in patients with systolic and diastolic hypertension, respectively, versus 2.5 months and 5.3 months in patients without hypertension (P<0.0001).
Objective response rates were 54.7% and 57.2% with hypertension compared with 9.7% and 25% without hypertension (P<0.0001).
The response rate did not differ significantly between patients who were taking antihypertensive medication at baseline and those who were not.
The safety analysis showed a similar incidence of any-grade and grade ≥3 cardiovascular, cerebrovascular, ocular, and renal adverse events in patients with and without hypertension.
“Patients with metastatic renal cell carcinoma on sunitinib treatment should be monitored in the clinic for hypertension and treated as necessary with antihypertensive medication with or without dose reduction, taking into account the findings reported here that use of antihypertensive agents did not reduce sunitinib antitumor activity and that maximum systolic blood pressure did not correlate with sunitinib dose intensity,” Rini and colleagues concluded in a poster presentation.
The study was supported by Pfizer.
Rini disclosed relationships with Pfizer, Wyeth, Genentech, and Novartis.
Primary source: Kidney Cancer Symposium
Source reference:
Rini B, et al “Hypertension is a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib” KCA 2009; Final program.
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KCA: Novel Agent Promising in Refractory RCC (CME/CE)
Posted by: admin in Prescription Cancer Drugs on August 13th, 2010
- Explain to patients that a novel drug might offer clinical benefits to patients who have kidney cancer that has progressed on two other types of therapy.
- Explain that the drug described in the study is not yet available.
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
CHICAGO — An inhibitor of protein kinase B may offer patients with metastatic renal cell carcinoma the possibility of additional clinical benefit after failure of multiple therapies, according to data reported here.
Treatment with perifosine led to one partial response and stable disease in half of a small group of patients who progressed after treatment with at least two prior therapies, Thomas E. Hutson, DO, PharmD, of Baylor University Medical Center in Dallas, said at the International Kidney Cancer Symposium.
Patients who achieved stable disease or better response had a median progression-free survival of 33 weeks, Hutson and his team found.
“Clearly, this is a drug that appears to have some degree of activity in a highly refractory patient population for which there is need for more therapy,” Hutson said. “How we are going to develop this agent further has yet to be defined, but combination strategies may be reasonable to pursue forward.”
Protein kinase B, or Akt, is a key component of a signal transduction pathway involved in cell growth, proliferation, migration, and apoptosis. Increased activation of Akt has been associated with poor prognosis in renal cell carcinoma.
At the American Society of Clinical Oncology meeting earlier this year, Hutson and colleagues reported that treatment with perifosine resulted in stable disease or better response in almost half of a group of patients with renal cell carcinoma who had progressed during treatment with an inhibitor of vascular endothelial growth factor (VEGF).
The study included a subset of 16 patients who had progressed after treatment with a VEGF inhibitor and an inhibitor of mammalian target of rapamycin (mTOR).
Here in Chicago, Hutson presented follow-up data on the 16 patients, which he characterized as having treatment-refractory disease.
The patients ranged in age from 50 to 80; 12 of the 16 were men, and 15 had clear-cell histology.
The patients received 100 mg of perifosine daily and were evaluated every 12 weeks. Patients who had objective response or stable disease continued treatment until progression or development of unacceptable toxicity.
One patient had a partial response and seven others had stable disease for more than 12 weeks.
The median progression-free survival for all 16 patients was 16 weeks, including 33 weeks for the 50% of patients who had stable disease or better response.
All but two of the patients remained alive as of late September, and the median overall survival had not been reached, said Hutson.
The study was supported by KERYX Biopharmaceuticals.
Hutson disclosed relationships with Pfizer, Bayer, Wyeth, Genentech, GlaxoSmithKline , AVEO, and Novartis.
Primary source: Kidney Cancer Symposium
Source reference:
Hutson TE et al. “Phase II study of perifosine in aptients with metastatic RCC progression after prior therapy with both a VEGF receptor inhibitor and an mTOR inhibitor” KCA 2009; Final Program.
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FDA Approves GlaxoSmithKline’s VOTRIENT(TM) For Advanced Renal Cell Cancer
Posted by: admin in Prescription Cancer Drugs on June 17th, 2010
GlaxoSmithKline (NYSE: GSK) announced that the U.S. Food and Drug Administration (FDA) has approved VOTRIENT(TM) (pazopanib) to treat patients with advanced renal cell carcinoma (RCC), a form of kidney cancer. Approximately 57,700 people in the U.S. will be diagnosed with kidney cancer this year, and 13,000 people will die from this disease.
“RCC is the most common malignancy of the kidney and is highly resistant to chemotherapy,” said Paolo Paoletti, MD, Senior Vice President, GlaxoSmithKline Oncology R&D Unit. “While treatment has improved in the past few years with the introduction of targeted therapies, advanced RCC remains a challenging disease. VOTRIENT will join existing targeted therapies to provide physicians with a new oral treatment option to their patients with advanced renal cell cancer.”
VOTRIENT, a once-daily, oral medication, is an angiogenesis inhibitor which may help prevent the growth of new blood vessels, thereby blocking the growth of kidney cancer tumors that need blood vessels to survive.
The approval of VOTRIENT was supported by a unanimous decision by the FDA’s Oncology Drugs Advisory Committee (ODAC) that the benefit-to-risk profile for VOTRIENT is acceptable for patients with advanced kidney cancer. The ODAC reviewed data from a Phase III clinical trial showing that VOTRIENT reduced the risk of tumor progression or death by 54 percent compared to placebo, regardless of prior treatment.
In this Phase III trial, the overall median PFS was 9.2 months with pazopanib and 4.2 months with placebo. Treatment-naive patients who received VOTRIENT experienced 11.1 months of median progression-free survival (PFS) versus 2.8 months with placebo. Additionally, patients who had previously received cytokine-based treatment achieved 7.4 months of median PFS with VOTRIENT versus 4.2 months with placebo.
The most common adverse events occurring in greater than or equal to 20% of subjects treated with VOTRIENT included diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. Grade 3/4 adverse events among these toxicities that differed by greater than or equal to 2% included abnormal liver function, hypertension, diarrhea, asthenia, and abdominal pain. Laboratory abnormalities occurring in >10% of patients and more commonly (greater than or equal to 5%) in the pazopanib arm included increased transaminases, hyperglycemia, leukopenia, hyperbilirubinemia, neutropenia, hypophosphatemia, thrombocytopenia, lymphocytopenia, hyponatremia, hypomagnesemia, and hypoglycemia. Drug-related deaths were observed in 1.4% of 290 patients and included hepatic failure (n=2), stroke (n=1), and perforation (n=1). Hepatic dysfunction is included as a boxed warning in the product label. Other Warnings and Precautions in the label relate to QT prolongation and torsade de pointes, hemorrhagic events, arterial thrombotic events, gastrointestinal perforation and fistula, hypertension, impaired wound healing, hypothyroidism, proteinuria, and pregnancy.
About GSK Oncology
GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK’s revolutionary ‘bench to bedside’ approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes collaborations with more than 160 cancer centers. GSK is closing in on cancer from all sides with a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.
GlaxoSmithKline - one of the world’s leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.
Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK’s operations are described under ‘Risk Factors’ in the ‘Business Review’ in the company’s Annual Report on Form 20-F for 2008.
Source: GlaxoSmithKline
ASCO: Trial May End Survival Advantage as Sign of Potency
Posted by: admin in Prescription Cancer Drugs on June 20th, 2009
ORLANDO, June 2 — Two major trials of interferon combined with a monoclonal antibody failed to show a survival advantage over interferon alone in treating advanced kidney cancer, researchers said here.
- Explain to interested patients that these trials failed to show a survival advantage for the drug combination being tested in kidney cancer but that may not mean the combination is without value.
- Note that because of the range of potent drugs available, it has become statistically difficult to see a difference in overall survival, since many patients are able to go on to second-line therapy with success.
- Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
The findings did not support earlier, more promising results showing improvements in progression-free survival, and they call into question the value of overall survival as a marker for the potency of a drug.
Both studies “left us a little bit disappointed,” said Nicholas Vogelzang, M.D., of the Nevada Cancer Institute, who discussed the studies at the annual meeting of the American Society of Clinical Oncology.
But paradoxically, missing the survival endpoint may be good news, he said, because it points to the “embarrassment of riches” in new, powerful drugs for renal cell carcinoma.
The overall survival attributable to the drugs in the trial becomes difficult to assess when patients can go on to other potent medications when their disease progresses, he said.
“Since survival is a moving target, progression-free survival and toxicity may need to become the new endpoints,” Dr. Vogelzang said.
Both studies compared interferon-alpha to interferon with bevacizumab (Avastin) in patients with metastatic renal cell carcinoma.
The Cancer and Leukemia Group B 90206 study, presented by Brian Rini, M.D., of the Cleveland Clinic Taussig Cancer Institute, found:
- Median overall survival was 18.3 months among patients getting the combination, compared with 17.4 months for interferon alone, but the difference did not reach statistical significance.
- Median progression-free survival, on the other hand, was 8.4 months for the combination, versus 4.9 months for interferon alone, which was highly significant at P<0.0001.
- Almost twice as many patients getting the combination had an objective response — 25.5% compared with 13.1% — which was also significant at P<0.0001.
About 54% of bevacizumab patients went on to another systemic therapy, as did 62% of those in the interferon arm, and that treatment significantly extended survival, Dr. Rini reported.
Among those in the bevacizumab arm who got second-line treatment, median overall survival was 31.4 months, compared with 13.1 months for those who did not.
In the interferon arm, the corresponding results were 26.8 and 9.1 months.
For those who got second-line therapy, the difference between the combination therapy and interferon alone approached statistical significance, at P=0.055, Dr. Rini reported.
The so-called Avoren study, presented by Bernard Escudier, M.D., of the Institut Gustave Roussy in Villejuif, France, found:
- Median overall survival was 23.3 months in the combination arm and 21.3 months in patients who got interferon and a placebo. The difference wasn’t significant.
- On the other hand, progression-free survival was 10.4 months in the combination arm and 5.5 in the interferon arm, which was significant at P<0.0001.
- The objective response rate was 31% in the bevacizumab patients and 12% in the group that got interferon and placebo, which again was significant at P<0.0001.
As in the other trial, many patients went on to have subsequent therapy — 55% in the bevacizumab arm and 63% in the interferon arm.
Among those who got second-line treatment, overall survival in the bevacizumab arm ranged from 38.6 to 43.6 months, compared with a range of 30.7 to 39.7 in the interferon arm, depending on the type of therapy.
None of the between-arm differences reached significance, although the patients initially treated with bevacizumab did better regardless of the type of therapy, Dr. Escudier said.
| The CALGB study was supported by the National Cancer Institute. Genentech and Schering-Plough supplied drugs for the trial.
Dr. Rini reported financial links with AVEO, Bayer, Genentech, Novartis, Pfizer, and Wyeth. The AVOREN study was supported by F. Hoffmann-La Roche. The researchers reported financial links to Antigenics, Bayer, GlaxoSmithKline , Inate Pharma, Novartis, Pfizer, Schering-Plough, F. Hoffmann-La Roche, sanofi-aventis, and Pfizer. Dr. Vogelzang reported financial links with Allos, Ambit, Amgen, Bayer, Celgene (U), Genentech, Keryx (U), Novartis, Onyx, Pfizer, Wilex, Arqule, Clinical Care Options, Cougar, Imedex, Lippincott Williams and Wilkins, Argos, AstraZeneca, Endocyte, GlaxoSmithKline , Keryx, and Medarex. |
Primary source: Journal of Clinical Oncology
Source reference:
Additional source: Journal of Clinical Oncology
Source reference:
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