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Priority Review Designation in NSCLC and 2018 GU Symposium Highlights

Gina Columbus
Published: Tuesday, Feb 20, 2018



Today-

A priority review designation in non-small cell lung cancer and highlights from the 2018 Genitourinary Cancers Symposium.

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

The FDA has granted a priority review designation to a new drug application for lorlatinib for use in patients with ALK-positive metastatic non-small cell lung cancer who have progressed on 1 or more ALK tyrosine kinase inhibitors.

The decision follows a breakthrough therapy designation awarded in April 2017. Pfizer, the developer of lorlatinib, which is a third-generation ALK inhibitor, announced in a news release that the European Medicines Agency and the Japan Pharmaceutical and Medical Devices Agency have also accepted applications to market lorlatinib for this indication.

The company submitted data from the phase II portion of a phase I/II trial in which the overall response rate was 69% in ALK-positive patients who were previously treated with crizotinib with or without chemotherapy. Additionally, the Intracranial ORR was 68%.

ALK-positive patients previously treated with a non-crizotinib ALK inhibitor with or without chemotherapy had an ORR of 33% and the IC-ORR was 42%. In those previously treated with 2 or 3 ALK inhibitors with or without chemotherapy, the ORR was 39% and IC-ORR was 48%.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make its final decision by August 2018.

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

The 2018 Genitourinary Cancers Symposium took place last week in San Francisco, California, highlighting a number of abstracts focused on targeted and immunotherapy data across renal cell carcinoma, bladder cancer, and prostate cancer.

For example, results of the phase III SPARTAN trial showed that apalutamide reduced the risk of metastasis or death by 72% in patients with nonmetastatic castration-resistant prostate cancer.

The SPARTAN trial evaluated the safety and efficacy of apalutamide versus placebo in patients with nonmetastatic CRPC and a rapidly rising prostate specific antigen level despite receiving continuous androgen deprivation therapy.

The median metastasis-free survival was 40.5 months in the apalutamide arm versus 16.2 months in the placebo arm. Based on these data, the FDA granted a priority review designation to apalutamide for use in this setting in December 2017. The agency is scheduled to make its final decision by the end of April 2018.

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

Also in prostate cancer, data from the phase III PROSPER trial showed that treatment with the combination of enzalutamide and androgen deprivation therapy reduced the risk of metastases or death by 71% versus ADT alone for patients with nonmetastatic castration-resistant disease.

In the double-blind study, the median metastasis-free survival was 36.6 months with enzalutamide plus ADT versus 14.7 months with ADT alone. Based on these findings, Pfizer and Astellas, the companies developing the antiandrogen agent, have already submitted a supplemental new drug application to the FDA.

Moreover, there was a 93% reduction in the risk of PSA progression in the enzalutamide arm compared with ADT alone. The median time to PSA progression in the enzalutamide group was 37.2 months compared with 3.9 months for ADT alone.

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

Also presented at the meeting were the findings from the phase III IMmotion151 trial, in which the combination of atezolizumab and bevacizumab reduced the risk of progression or death by 26% versus sunitinib for patients with untreated PD-L1-positive metastatic renal cell carcinoma.

Results showed that the median progression-free survival after 15 months of median follow-up was 11.2 months with atezolizumab and bevacizumab compared with 7.7 months with sunitinib.

OS data remained immature at the time of the interim analysis. In the PD-L1 cohort, the median OS was not yet reached with the combination compared with 23.3 months for sunitinib, representing an early 32% reduction in the risk of death with the combination versus monotherapy. In the ITT group, median OS was not reached in both arms.

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

The combination of olaparib and durvalumab showed promising clinical activity in patients with metastatic castration-resistant prostate cancer, according to phase II findings presented at the symposium.

Data from the trial included the first 17 patients of an ongoing study at the National Cancer Institute. They received olaparib at 300 mg orally every 12 hours plus durvalumab at 1500 mg intravenously every 28 days.

Results showed that 12 of these patients had reductions in prostate-specific antigen level, with 8 having PSA declines of more than 50%.

The median radiographic progression-free survival was 16.1 months in the overall cohort. Additionally, patients with mutations in DNA damage repair pathways had superior median PFS compared with men without known mutations in DNA damage repair pathways.

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

Finally, in urothelial cancer, 2-year follow-up data from the phase III KEYNOTE-045 study presented at the meeting demonstrated sustained improvements in overall survival with pembrolizumab over chemotherapy in pretreated patients with locally advanced or recurrent disease.

This trial was the basis for the FDA's approval of pembrolizumab in the second-line setting for patients with urothelial carcinoma in May 2017, based on the initial analysis of KEYNOTE-045.

After median follow-up of 27.7 months, median OS was 10.3 months for patients treated with pembrolizumab versus 7.3 months for those randomized to chemotherapy. The risk of death was reduced by 30% with pembrolizumab compared with chemotherapy as a second-line treatment following disease progression on platinum-based chemotherapy.

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

This week, we sat down with Dr Tanios Bekaii-Saab of Mayo Clinic, to discuss how physicians decide on the duration of adjuvant therapy for patients with colorectal cancer.

That's all for today.

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

A priority review designation in non-small cell lung cancer and highlights from the 2018 Genitourinary Cancers Symposium.

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

The FDA has granted a priority review designation to a new drug application for lorlatinib for use in patients with ALK-positive metastatic non-small cell lung cancer who have progressed on 1 or more ALK tyrosine kinase inhibitors.

The decision follows a breakthrough therapy designation awarded in April 2017. Pfizer, the developer of lorlatinib, which is a third-generation ALK inhibitor, announced in a news release that the European Medicines Agency and the Japan Pharmaceutical and Medical Devices Agency have also accepted applications to market lorlatinib for this indication.

The company submitted data from the phase II portion of a phase I/II trial in which the overall response rate was 69% in ALK-positive patients who were previously treated with crizotinib with or without chemotherapy. Additionally, the Intracranial ORR was 68%.

ALK-positive patients previously treated with a non-crizotinib ALK inhibitor with or without chemotherapy had an ORR of 33% and the IC-ORR was 42%. In those previously treated with 2 or 3 ALK inhibitors with or without chemotherapy, the ORR was 39% and IC-ORR was 48%.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make its final decision by August 2018.

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

The 2018 Genitourinary Cancers Symposium took place last week in San Francisco, California, highlighting a number of abstracts focused on targeted and immunotherapy data across renal cell carcinoma, bladder cancer, and prostate cancer.

For example, results of the phase III SPARTAN trial showed that apalutamide reduced the risk of metastasis or death by 72% in patients with nonmetastatic castration-resistant prostate cancer.

The SPARTAN trial evaluated the safety and efficacy of apalutamide versus placebo in patients with nonmetastatic CRPC and a rapidly rising prostate specific antigen level despite receiving continuous androgen deprivation therapy.

The median metastasis-free survival was 40.5 months in the apalutamide arm versus 16.2 months in the placebo arm. Based on these data, the FDA granted a priority review designation to apalutamide for use in this setting in December 2017. The agency is scheduled to make its final decision by the end of April 2018.

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

Also in prostate cancer, data from the phase III PROSPER trial showed that treatment with the combination of enzalutamide and androgen deprivation therapy reduced the risk of metastases or death by 71% versus ADT alone for patients with nonmetastatic castration-resistant disease.

In the double-blind study, the median metastasis-free survival was 36.6 months with enzalutamide plus ADT versus 14.7 months with ADT alone. Based on these findings, Pfizer and Astellas, the companies developing the antiandrogen agent, have already submitted a supplemental new drug application to the FDA.

Moreover, there was a 93% reduction in the risk of PSA progression in the enzalutamide arm compared with ADT alone. The median time to PSA progression in the enzalutamide group was 37.2 months compared with 3.9 months for ADT alone.

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

Also presented at the meeting were the findings from the phase III IMmotion151 trial, in which the combination of atezolizumab and bevacizumab reduced the risk of progression or death by 26% versus sunitinib for patients with untreated PD-L1-positive metastatic renal cell carcinoma.

Results showed that the median progression-free survival after 15 months of median follow-up was 11.2 months with atezolizumab and bevacizumab compared with 7.7 months with sunitinib.

OS data remained immature at the time of the interim analysis. In the PD-L1 cohort, the median OS was not yet reached with the combination compared with 23.3 months for sunitinib, representing an early 32% reduction in the risk of death with the combination versus monotherapy. In the ITT group, median OS was not reached in both arms.

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

The combination of olaparib and durvalumab showed promising clinical activity in patients with metastatic castration-resistant prostate cancer, according to phase II findings presented at the symposium.

Data from the trial included the first 17 patients of an ongoing study at the National Cancer Institute. They received olaparib at 300 mg orally every 12 hours plus durvalumab at 1500 mg intravenously every 28 days.

Results showed that 12 of these patients had reductions in prostate-specific antigen level, with 8 having PSA declines of more than 50%.

The median radiographic progression-free survival was 16.1 months in the overall cohort. Additionally, patients with mutations in DNA damage repair pathways had superior median PFS compared with men without known mutations in DNA damage repair pathways.

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

Finally, in urothelial cancer, 2-year follow-up data from the phase III KEYNOTE-045 study presented at the meeting demonstrated sustained improvements in overall survival with pembrolizumab over chemotherapy in pretreated patients with locally advanced or recurrent disease.

This trial was the basis for the FDA's approval of pembrolizumab in the second-line setting for patients with urothelial carcinoma in May 2017, based on the initial analysis of KEYNOTE-045.

After median follow-up of 27.7 months, median OS was 10.3 months for patients treated with pembrolizumab versus 7.3 months for those randomized to chemotherapy. The risk of death was reduced by 30% with pembrolizumab compared with chemotherapy as a second-line treatment following disease progression on platinum-based chemotherapy.

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

This week, we sat down with Dr Tanios Bekaii-Saab of Mayo Clinic, to discuss how physicians decide on the duration of adjuvant therapy for patients with colorectal cancer.

That's all for today.

Thank you for watching OncLive News Network! I'm Gina Columbus.
 
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