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Priority Review Designations in RCC and NSCLC, Promising Results in HCC Trial, and More

Gina Columbus
Published: Monday, Oct 23, 2017



Today-

Priority review designations in renal cell carcinoma and non–small cell lung cancer, encouraging findings in a liver cancer trial, promising results with an immunotherapy combination in small cell lung cancer, and recommendations for European approvals in prostate cancer and NSCLC.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has granted a priority review to a supplemental new drug application for cabozantinib for previously untreated patients with advanced renal cell carcinoma.

The sNDA is based on data from the phase II CABOSUN trial, in which an independent data review showed that cabozantinib reduced the risk of progression or death by 52% versus sunitinib as a first-line treatment for patients with metastatic RCC. The median progression-free survival was 3.3 months longer with cabozantinib versus sunitinib, at 8.6 versus 5.3 months.

Additionally, the median overall survival was 26.6 months in the cabozantinib arm versus 21.2 months in the sunitinib arm.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make its decision on the application by February 15, 2018.

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The FDA also granted a priority review to a supplemental biologics license application for durvalumab as a treatment for patients with stage III, unresectable non–small cell lung cancer whose disease has not progressed following platinum-based chemoradiation therapy.

The designation is based on positive progression-free survival results from the PACIFIC trial, in which the median PFS from randomization showed an 11.2-month benefit associated with the experimental arm.

Additionally, the 12-month PFS rate was 55.9% versus 35.3%, and the 18-month PFS rate was 44.2% versus 27.0%, again favoring the durvalumab arm. OS data are still immature and were not included in this analysis.

Objective response rate, as assessed by blinded independent central review, was also significantly higher with durvalumab, at 28.4% versus 16%. Of the patients who had a response to durvalumab, 72.8% had an ongoing response at both 12 and 18 months as compared with 56.1% and 46.8%, respectively, in the placebo arm.

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In hepatocellular carcinoma, phase III findings of the CELESTIAL trial showed that cabozantinib also improved overall survival compared with placebo in patients with advanced disease who have previously received sorafenib.

An independent monitoring committee has recommended stopping the study for efficacy following review of the second planned interim analysis. Exelixis and Ipsen, the co-developers of the multikinase inhibitor, have not released data from CELESTIAL, reporting that detailed results will be presented at an upcoming medical meeting.

The randomized, global phase III CELESTIAL trial examined cabozantinib versus placebo in patients with advanced HCC who received up to 2 prior systemic cancer therapies for HCC and had adequate liver function.

**************************************

A study presented during the IASLC World Conference on Lung Cancer showed that the combination of nivolumab plus ipilimumab induced an objective response rate of 46% in patients with recurrent small cell lung cancer with high tumor mutation burden, or TMB.

The ORR was 21% with nivolumab monotherapy in patients with high TMB.

The findings were from an exploratory analysis of the phase I/II CheckMate-032 study.

In patients with medium and low levels of TMB treated with the combination, the ORR was 16% and 22%, respectively. The ORR was 7% and 5%, respectively, among patients in these populations receiving single-agent nivolumab.

Among patients with high TMB, the 1-year overall survival rate was 62% with the combination and 35% with single-agent nivolumab. This compared with 1-year OS rates of 20% and 26%, and 23% and 22%, with the combination and monotherapy in patients with medium and low levels of TMB, respectively.

*****************************************

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of alectinib for the first-line treatment of adults with ALK-positive, advanced non–small cell lung cancer.

The CHMP also simultaneously recommended converting the current conditional marketing authorization for alectinib following failure with crizotinib to a full marketing authorization.

The positive recommendations are based on phase III results from the ALEX trial showing that the second-generation ALK-inhibitor significantly reduced the risk of progression or death compared with crizotinib in treatment-naïve patients with ALK-positive NSCLC.

In the ALEX study, alectinib improved progression-free survival by 53% compared with crizotinib. The primary endpoint of investigator-reported median PFS has not been reached in the alectinib arm compared with 11.1 months in the crizotinib arm.

This is the second phase III trial to show that alectinib outperforms crizotinib in frontline ALK-positive NSCLC. In the Japanese open-label phase III J-ALEX study, alectinib improved PFS by 66% versus crizotinib.

*************************************

In prostate cancer, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended expanding the existing marketing authorization for abiraterone acetate to include use in combination with prednisone/prednisolone and androgen deprivation therapy in men with newly diagnosed, high-risk metastatic hormone-sensitive disease.

The positive opinion was based on findings from the phase III LATITUDE trial, results of which showed that abiraterone combined with prednisone/prednisolone and ADT reduced the risk of death by 38% versus ADT and placebo in men with high-risk metastatic, castration-sensitive prostate cancer.

Moreover, the median overall survival was not reached with abiraterone acetate versus 34.7 months with placebo.

The European Commission has already approved abiraterone acetate in combination with prednisone or prednisolone for the treatment of mCRPC in adult men who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated. It is also approved for mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy.

*****************************************

This week, we sat down with Dr Leora Horn of Vanderbilt-Ingram Cancer Center to discuss the early promise of ensartinib for patients with ALK-positive non–small cell lung cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
 
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Today-

Priority review designations in renal cell carcinoma and non–small cell lung cancer, encouraging findings in a liver cancer trial, promising results with an immunotherapy combination in small cell lung cancer, and recommendations for European approvals in prostate cancer and NSCLC.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has granted a priority review to a supplemental new drug application for cabozantinib for previously untreated patients with advanced renal cell carcinoma.

The sNDA is based on data from the phase II CABOSUN trial, in which an independent data review showed that cabozantinib reduced the risk of progression or death by 52% versus sunitinib as a first-line treatment for patients with metastatic RCC. The median progression-free survival was 3.3 months longer with cabozantinib versus sunitinib, at 8.6 versus 5.3 months.

Additionally, the median overall survival was 26.6 months in the cabozantinib arm versus 21.2 months in the sunitinib arm.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make its decision on the application by February 15, 2018.

*****************************************

The FDA also granted a priority review to a supplemental biologics license application for durvalumab as a treatment for patients with stage III, unresectable non–small cell lung cancer whose disease has not progressed following platinum-based chemoradiation therapy.

The designation is based on positive progression-free survival results from the PACIFIC trial, in which the median PFS from randomization showed an 11.2-month benefit associated with the experimental arm.

Additionally, the 12-month PFS rate was 55.9% versus 35.3%, and the 18-month PFS rate was 44.2% versus 27.0%, again favoring the durvalumab arm. OS data are still immature and were not included in this analysis.

Objective response rate, as assessed by blinded independent central review, was also significantly higher with durvalumab, at 28.4% versus 16%. Of the patients who had a response to durvalumab, 72.8% had an ongoing response at both 12 and 18 months as compared with 56.1% and 46.8%, respectively, in the placebo arm.

******************************

In hepatocellular carcinoma, phase III findings of the CELESTIAL trial showed that cabozantinib also improved overall survival compared with placebo in patients with advanced disease who have previously received sorafenib.

An independent monitoring committee has recommended stopping the study for efficacy following review of the second planned interim analysis. Exelixis and Ipsen, the co-developers of the multikinase inhibitor, have not released data from CELESTIAL, reporting that detailed results will be presented at an upcoming medical meeting.

The randomized, global phase III CELESTIAL trial examined cabozantinib versus placebo in patients with advanced HCC who received up to 2 prior systemic cancer therapies for HCC and had adequate liver function.

**************************************

A study presented during the IASLC World Conference on Lung Cancer showed that the combination of nivolumab plus ipilimumab induced an objective response rate of 46% in patients with recurrent small cell lung cancer with high tumor mutation burden, or TMB.

The ORR was 21% with nivolumab monotherapy in patients with high TMB.

The findings were from an exploratory analysis of the phase I/II CheckMate-032 study.

In patients with medium and low levels of TMB treated with the combination, the ORR was 16% and 22%, respectively. The ORR was 7% and 5%, respectively, among patients in these populations receiving single-agent nivolumab.

Among patients with high TMB, the 1-year overall survival rate was 62% with the combination and 35% with single-agent nivolumab. This compared with 1-year OS rates of 20% and 26%, and 23% and 22%, with the combination and monotherapy in patients with medium and low levels of TMB, respectively.

*****************************************

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of alectinib for the first-line treatment of adults with ALK-positive, advanced non–small cell lung cancer.

The CHMP also simultaneously recommended converting the current conditional marketing authorization for alectinib following failure with crizotinib to a full marketing authorization.

The positive recommendations are based on phase III results from the ALEX trial showing that the second-generation ALK-inhibitor significantly reduced the risk of progression or death compared with crizotinib in treatment-naïve patients with ALK-positive NSCLC.

In the ALEX study, alectinib improved progression-free survival by 53% compared with crizotinib. The primary endpoint of investigator-reported median PFS has not been reached in the alectinib arm compared with 11.1 months in the crizotinib arm.

This is the second phase III trial to show that alectinib outperforms crizotinib in frontline ALK-positive NSCLC. In the Japanese open-label phase III J-ALEX study, alectinib improved PFS by 66% versus crizotinib.

*************************************

In prostate cancer, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended expanding the existing marketing authorization for abiraterone acetate to include use in combination with prednisone/prednisolone and androgen deprivation therapy in men with newly diagnosed, high-risk metastatic hormone-sensitive disease.

The positive opinion was based on findings from the phase III LATITUDE trial, results of which showed that abiraterone combined with prednisone/prednisolone and ADT reduced the risk of death by 38% versus ADT and placebo in men with high-risk metastatic, castration-sensitive prostate cancer.

Moreover, the median overall survival was not reached with abiraterone acetate versus 34.7 months with placebo.

The European Commission has already approved abiraterone acetate in combination with prednisone or prednisolone for the treatment of mCRPC in adult men who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated. It is also approved for mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy.

*****************************************

This week, we sat down with Dr Leora Horn of Vanderbilt-Ingram Cancer Center to discuss the early promise of ensartinib for patients with ALK-positive non–small cell lung cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
 
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TitleExpiration DateCME Credits
Cancer Summaries and Commentaries™: Update from Chicago: Advances in the Treatment of Breast CancerJul 31, 20181.0
Community Practice Connections™: The Next Generation in Renal Cell Carcinoma Treatment: An Oncology Nursing Essentials WorkshopJul 31, 20181.5
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