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FDA Approvals in CINV and HER2+ Breast Cancer, Priority Review in Myelofibrosis, and More

Kristi Rosa
Published: Saturday, Mar 09, 2019



Today-

FDA approvals in chemotherapy-induced nausea and vomiting and of a new dosing regimen in breast cancer, priority review designation in myelofibrosis, disappointing findings in an ovarian cancer trial, and European recommendations for a checkpoint inhibitor.

Welcome to OncLive News Network! I'm Kristi Rosa.

The FDA has expanded the approval of aprepitant injectable emulsion to include a 2-minute intravenous use for the prevention of acute and delayed chemotherapy-induced nausea and vomiting.

The approval is based on results of a two-part, phase I study that demonstrated bioequivalence and a similar safety profile for patients who received aprepitant as a standard 30-minute IV infusion compared with a 2-minute IV injection.

Aprepitant is a polysorbate 80-free, IV formulation of an NK1 receptor antagonist, which is designed to significantly reduce CINV in both the acute and delayed phases following chemotherapy. The FDA previously approved aprepitant as a 30-minute IV infusion in November 2017, making it the first IV formulation to directly deliver aprepitant, which is the active ingredient in fosaprepitant capsules.

Regarding safety, 8 patients on the injection arm experienced 11 treatment-emergent adverse events compared with 9 patients who experienced 14 treatment-emergent adverse events in the infusion group.

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

In breast cancer, the FDA has approved subcutaneous use of trastuzumab and hyaluronidase-oysk injection, known by the trade name Herceptin Hylecta, in combination with chemotherapy for the treatment of patients with HER2-positive early disease, in combination with paclitaxel in patients with metastatic HER2-positive breast cancer as a frontline treatment, and alone for patients with metastatic disease who have received at least 1 prior chemotherapy regimen.

The approval is based on findings from the HannaH and SafeHER studies, in which Herceptin Hylecta demonstrated comparable rates of efficacy and safety compared with the standard intravenous use of trastuzumab, as well as the PrefHER trial, which suggested a patient preference for the subcutaneous regimen.

In HannaH, results showed that the 45.4% pathologic complete response rate with Herceptin Hylecta was similar to the 40.7% pCR rate in the IV trastuzumab arm, demonstrating noninferior levels in pharmacokinetics and noninferior clinical efficacy. In SafeHER, results showed that there were no safety signals with Herceptin Hylecta and the safety profile was consistent with what was been previously associated with standard trastuzumab.

Finally, in the patient-preference PrefHER study, results showed that 86% of patients on the trial preferred the subcutaneous regimen versus 13% who preferred standard IV trastuzumab, and 1% of patients had no preference.

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

The FDA has granted a priority review designation to a new drug application for fedratinib as a treatment for patients with myelofibrosis.

The designation is based on results from the phase III JAKARTA and phase II JAKARTA-2 trials, results of both trials demonstrated a significant reduction in splenomegaly and symptom burden in patients with myelofibrosis.

The designation follows a clinical hold placed by the FDA in November 2013, citing potential cases of Wernicke's encephalopathy reported in clinical trials, but the hold was lifted in August 2017.

In the phase III JAKARTA trial, patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytopenia myelofibrosis were randomized to receive fedratinib orally at 400 or 500 mg daily, or placebo, for at least 6 consecutive 4-week cycles.

Results showed that spleen response was achieved by 36% and 40% of patients who received fedratinib at the 400- and 500-mg doses, respectively, compared with 1% of patients who were on the placebo arm.

In the phase II JAKARTA-2 trial, fedratinib was evaluated in patients with primary or secondary myelofibrosis who previously received ruxolitinib and were resistant or intolerant after 14 days of treatment.

Results showed that 55% achieved a spleen response, suggesting that patients with ruxolitinib-resistant or -intolerant myelofibrosis could achieve a significant clinical benefit with fedratinib.

Under the Prescription Drug User Fee Act, the FDA is expected to make a decision on the NDA by September 3, 2019.

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

In ovarian cancer, the antibody-drug conjugate mirvetuximab soravtansine did not improve progression-free survival compared with chemotherapy in patients with folate receptor alpha-positive, platinum-resistant disease and in an overall patient population, missing the primary endpoint of the phase III FORWARD I trial.

There was no significant difference in PFS in the overall study population, and although the PFS was longer with mirvetuximab soravtansine in the prespecified high folate receptor alpha-positive subgroup, it did not reach statistical significance as per a prespecified statistical analysis plan.

Under this statistical analysis plan, it was determined that if the P value of the primary endpoint in either population is greater than .05, then the P value in the other population must be less than or equal to .025 to achieve statistical significance.

In addition to the PFS data, the confirmed ORR in the overall study population was 22% for mirvetuximab soravtansine and 12% for chemotherapy. There was no significant difference in PFS in the overall study population.

In the pre-specified high FR-alpha subgroup, PFS was longer in those who received mirvetuximab soravtansine versus chemotherapy, but it did not reach statistical significance. In this subgroup, the confirmed ORRs were 24% and 10% for mirvetuximab soravtansine and chemotherapy, respectively. Moreover, OS was longer in the mirvetuximab soravtansine arm.

Additional findings will be presented at an upcoming medical meeting.

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

The European Medicines Agency's Committee for Medicinal Products for Human Use has adopted a positive opinion for a new extended dosing schedule for pembrolizumab for all of the PD-1 inhibitor's monotherapy indications in the European Union.

The recommendation supports a new suggested dose of single-agent pembrolizumab at 400 milligrams every 6 weeks delivered as an intravenous infusion over 30 minutes. If approved by the European Commission, the every-6-weeks dose would be available in addition to the currently indicated dose of 200 milligrams every 3 weeks that is infused over 30 minutes.

Results of a study that were presented at the 2018 ASCO Annual Meeting evaluated the 6-weekly dosing schedule of pembrolizumab using a modeling- and simulation-based approach to determine whether a longer dosing interval would provide greater flexibility and convenience to patients and healthcare providers.

Investigators concluded that the 2 dosing regimens are expected to have a similar benefit-risk profile, suggesting physicians could have the flexibility to dose at a frequency that is tailored toward patients' needs and/or personal preferences.

Pembrolizumab is currently indicated as monotherapy for select pastients with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, urothelial carcinoma, gastric or gastroesophageal cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, microsatellite instability-high or mismatch repair deficient solid tumors, colorectal cancer, cervical cancer, and hepatocellular carcinoma,

The European Commission will now review the CHMP's opinion, and a final decision on a marketing authorization is expected in the second quarter of 2019.

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

This week, we sat down with Dr Brad Kahl, of Washington University School of Medicine, to discuss genomic profiling in chronic lymphocytic leukemia.

That's all for today.

Thank you for watching OncLive News Network! I'm Kristi Rosa.
 
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Today-

FDA approvals in chemotherapy-induced nausea and vomiting and of a new dosing regimen in breast cancer, priority review designation in myelofibrosis, disappointing findings in an ovarian cancer trial, and European recommendations for a checkpoint inhibitor.

Welcome to OncLive News Network! I'm Kristi Rosa.

The FDA has expanded the approval of aprepitant injectable emulsion to include a 2-minute intravenous use for the prevention of acute and delayed chemotherapy-induced nausea and vomiting.

The approval is based on results of a two-part, phase I study that demonstrated bioequivalence and a similar safety profile for patients who received aprepitant as a standard 30-minute IV infusion compared with a 2-minute IV injection.

Aprepitant is a polysorbate 80-free, IV formulation of an NK1 receptor antagonist, which is designed to significantly reduce CINV in both the acute and delayed phases following chemotherapy. The FDA previously approved aprepitant as a 30-minute IV infusion in November 2017, making it the first IV formulation to directly deliver aprepitant, which is the active ingredient in fosaprepitant capsules.

Regarding safety, 8 patients on the injection arm experienced 11 treatment-emergent adverse events compared with 9 patients who experienced 14 treatment-emergent adverse events in the infusion group.

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

In breast cancer, the FDA has approved subcutaneous use of trastuzumab and hyaluronidase-oysk injection, known by the trade name Herceptin Hylecta, in combination with chemotherapy for the treatment of patients with HER2-positive early disease, in combination with paclitaxel in patients with metastatic HER2-positive breast cancer as a frontline treatment, and alone for patients with metastatic disease who have received at least 1 prior chemotherapy regimen.

The approval is based on findings from the HannaH and SafeHER studies, in which Herceptin Hylecta demonstrated comparable rates of efficacy and safety compared with the standard intravenous use of trastuzumab, as well as the PrefHER trial, which suggested a patient preference for the subcutaneous regimen.

In HannaH, results showed that the 45.4% pathologic complete response rate with Herceptin Hylecta was similar to the 40.7% pCR rate in the IV trastuzumab arm, demonstrating noninferior levels in pharmacokinetics and noninferior clinical efficacy. In SafeHER, results showed that there were no safety signals with Herceptin Hylecta and the safety profile was consistent with what was been previously associated with standard trastuzumab.

Finally, in the patient-preference PrefHER study, results showed that 86% of patients on the trial preferred the subcutaneous regimen versus 13% who preferred standard IV trastuzumab, and 1% of patients had no preference.

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

The FDA has granted a priority review designation to a new drug application for fedratinib as a treatment for patients with myelofibrosis.

The designation is based on results from the phase III JAKARTA and phase II JAKARTA-2 trials, results of both trials demonstrated a significant reduction in splenomegaly and symptom burden in patients with myelofibrosis.

The designation follows a clinical hold placed by the FDA in November 2013, citing potential cases of Wernicke's encephalopathy reported in clinical trials, but the hold was lifted in August 2017.

In the phase III JAKARTA trial, patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytopenia myelofibrosis were randomized to receive fedratinib orally at 400 or 500 mg daily, or placebo, for at least 6 consecutive 4-week cycles.

Results showed that spleen response was achieved by 36% and 40% of patients who received fedratinib at the 400- and 500-mg doses, respectively, compared with 1% of patients who were on the placebo arm.

In the phase II JAKARTA-2 trial, fedratinib was evaluated in patients with primary or secondary myelofibrosis who previously received ruxolitinib and were resistant or intolerant after 14 days of treatment.

Results showed that 55% achieved a spleen response, suggesting that patients with ruxolitinib-resistant or -intolerant myelofibrosis could achieve a significant clinical benefit with fedratinib.

Under the Prescription Drug User Fee Act, the FDA is expected to make a decision on the NDA by September 3, 2019.

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

In ovarian cancer, the antibody-drug conjugate mirvetuximab soravtansine did not improve progression-free survival compared with chemotherapy in patients with folate receptor alpha-positive, platinum-resistant disease and in an overall patient population, missing the primary endpoint of the phase III FORWARD I trial.

There was no significant difference in PFS in the overall study population, and although the PFS was longer with mirvetuximab soravtansine in the prespecified high folate receptor alpha-positive subgroup, it did not reach statistical significance as per a prespecified statistical analysis plan.

Under this statistical analysis plan, it was determined that if the P value of the primary endpoint in either population is greater than .05, then the P value in the other population must be less than or equal to .025 to achieve statistical significance.

In addition to the PFS data, the confirmed ORR in the overall study population was 22% for mirvetuximab soravtansine and 12% for chemotherapy. There was no significant difference in PFS in the overall study population.

In the pre-specified high FR-alpha subgroup, PFS was longer in those who received mirvetuximab soravtansine versus chemotherapy, but it did not reach statistical significance. In this subgroup, the confirmed ORRs were 24% and 10% for mirvetuximab soravtansine and chemotherapy, respectively. Moreover, OS was longer in the mirvetuximab soravtansine arm.

Additional findings will be presented at an upcoming medical meeting.

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

The European Medicines Agency's Committee for Medicinal Products for Human Use has adopted a positive opinion for a new extended dosing schedule for pembrolizumab for all of the PD-1 inhibitor's monotherapy indications in the European Union.

The recommendation supports a new suggested dose of single-agent pembrolizumab at 400 milligrams every 6 weeks delivered as an intravenous infusion over 30 minutes. If approved by the European Commission, the every-6-weeks dose would be available in addition to the currently indicated dose of 200 milligrams every 3 weeks that is infused over 30 minutes.

Results of a study that were presented at the 2018 ASCO Annual Meeting evaluated the 6-weekly dosing schedule of pembrolizumab using a modeling- and simulation-based approach to determine whether a longer dosing interval would provide greater flexibility and convenience to patients and healthcare providers.

Investigators concluded that the 2 dosing regimens are expected to have a similar benefit-risk profile, suggesting physicians could have the flexibility to dose at a frequency that is tailored toward patients' needs and/or personal preferences.

Pembrolizumab is currently indicated as monotherapy for select pastients with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, urothelial carcinoma, gastric or gastroesophageal cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, microsatellite instability-high or mismatch repair deficient solid tumors, colorectal cancer, cervical cancer, and hepatocellular carcinoma,

The European Commission will now review the CHMP's opinion, and a final decision on a marketing authorization is expected in the second quarter of 2019.

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

This week, we sat down with Dr Brad Kahl, of Washington University School of Medicine, to discuss genomic profiling in chronic lymphocytic leukemia.

That's all for today.

Thank you for watching OncLive News Network! I'm Kristi Rosa.
 
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