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FDA Approvals in NETs, Breast Cancer, AML, a Biosimilar, and More

Gina Columbus
Published: Monday, Aug 06, 2018



Today-

FDA approvals in neuroendocrine tumors, breast cancer, acute myeloid leukemia, and of a biosimilar, and breakthrough therapy designations in endometrial cancer and acute myeloid leukemia.

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

The FDA has approved iobenguane I-131, known by the trade name Azedra, for adult and pediatric patients aged more than 12 years old with iobenguane scan–positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.

The decision was based on findings from a phase IIb trial that was conducted under the FDA's special protocol assessment. In the study, the radiopharmaceutical elicited a greater than 50% reduction in antihypertensive medication use for more than 6 months for 25% of patients with PPGL. In those receiving at least 2 therapeutic doses, this was achieved for 32% of patients.

Iobenguane I-131 is made using UltraTrace, which results in less non-radioactive MIBG during enrichment, leading to greater delivery of radiation to the tumor. The UltraTrace technology was developed by Molecular Insight Pharmaceuticals, which was later acquired by Progenics in 2013.

The novel agent was previously granted a breakthrough therapy designation for the treatment of PPGL, along with orphan drug and fast track designations. An expanded access program for iobenguane I-131 is currently available for patients with MIBG-avid malignant and/or recurrent PPGL. The program also plans to further assess safety.

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In breast cancer, the FDA has approved the Magtrace and Sentimag Magnetic Localization System used to guide lymph node biopsies in women undergoing mastectomy. The system uses magnetic detection to identify sentinel lymph nodes for surgical removal.

The magnetic Magtrace particles are injected into the patient’s breast tissue and become trapped in the lymph nodes. The surgeon then applies the Sentimag probe to the patients’ skin near the tumor site, and detects the magnetic particles located within the sentinel lymph node. That node is then removed and tested for the presence of cancer cells.

Endomag, the system’s manufacturer, stated the device is less invasive than wire-guided localization and allows greater flexibility in scheduling for patients, surgeons, and radiologists.

Endomag submitted updated data from the open-label, multicenter, paired comparison SentimagIC trial evaluating Magtrace versus a Technetium 99-labeled sulfur colloid radioisotope/isosulfan blue dye control. The study met the primary endpoint of noninferiority for lymph node detection rate.

Endomag received FDA approval for Sentimag and the marker technology Magseed in 2016.

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

The FDA approved filgrastim-aafi, known by the trade name Nivestym, a filgrastim biosimilar, to prevent and treat adverse events associated with cancer treatment, including febrile neutropenia and severe neutropenia.

This is the second filgrastim biosimilar approved for use in the United States following the 2015 approval of EP2006.

Filgrastim-aafi is indicated to reduce the incidence and duration of these side effects in patients with nonmyeloid malignancies undergoing myelosuppressive therapy, those with acute myeloid leukemia following induction or consolidation chemotherapy, patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation, those with chronic congenital, cyclic, or idiopathic neutropenia, and patients undergoing autologous hematopoietic progenitor cell collection and treatment.

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

In acute myeloid leukemia, the FDA has approved ivosidenib, known by the trade name Tibsovo, for the treatment of adult patients with relapsed/refractory IDH1-mutant disease.

The approval was based on findings of a single-arm phase I study of 174 patients with IDH1-positive relapsed/refractory AML. Results showed that the complete remission rate was 24.7% and the CR with partial hematologic improvement rate was 8%. Moreover, the median duration of CR plus CRh was 8.2 months. Among the CR/CRh population, the median time to best response was 2.0 months.

Regarding safety, all-grade adverse events occurring in more than 20% of patients included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, electrocardiogram QT prolonged, rash, pyrexia, cough and constipation. The most common serious AEs occurring in at least 5% of patients included differentiation syndrome, leukocytosis, and electrocardiogram QT prolonged.

The FDA label for ivosidenib includes a boxed warning regarding differentiation syndrome, warning that the condition can be fatal if not treated.

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

The FDA has granted a breakthrough therapy designation to the combination of lenvatinib and pembrolizumab for the treatment of patients with advanced and/or metastatic non–microsatellite instability high/proficient mismatch repair endometrial carcinoma who have progressed after more than 1 prior systemic therapy.

The decision was based on interim data from the phase Ib/II basket Study 111/KEYNOTE-146 trial, which were presented at the 2018 ASCO Annual Meeting. In the 53-patient endometrial cancer cohort, the objective response rate at week 24 per independent radiology review was 45.3% with the combination. The overall ORR was 47.2%, including 3 complete responses and 25 partial responses.

Moreover, the median PFS with the combination was 7.4 months. Nineteen patients had stable disease and 5 had progressive disease. The median duration of response was not estimable. Overall, 79.3% of patients had a duration of response lasting longer than 12 months.

This combination was previously granted a breakthrough therapy designation by the FDA in January 2018 for the treatment of patients with advanced and/or metastatic renal cell carcinoma.

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

In acute myeloid leukemia, the FDA has granted a breakthrough therapy designation to quizartinib for the treatment of adult patients with relapsed/refractory FLT3-ITD–positive acute myeloid leukemia.

The designation is based on data from the phase III QuANTUM-R study, in which the FLT3 inhibitor reduced the risk of disease progression or death by 24% versus salvage chemotherapy in patients with FLT3-ITD–positive relapsed/refractory AML after frontline treatment with or without hematopoietic stem cell transplantation.

At a median follow-up of 23.5 months, the median overall survival was 6.2 months with quizartinib compared with 4.7 months with salvage chemotherapy.

Data from the QuANTUM-R study confirmed the efficacy and safety of quizartinib that was observed in previous trials and showed the value of therapy targeting FLT3-ITD. It is the first trial to demonstrate improved overall survival for patients with FLT3-ITD–associated AML who are treatment resistant or who relapsed after prior therapy.

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

This week, we sat down with Dr Alexander Drilon, of Memorial Sloan Kettering Cancer Center, to discuss ongoing challenges with TRK inhibition.

That’s all for today.

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

FDA approvals in neuroendocrine tumors, breast cancer, acute myeloid leukemia, and of a biosimilar, and breakthrough therapy designations in endometrial cancer and acute myeloid leukemia.

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

The FDA has approved iobenguane I-131, known by the trade name Azedra, for adult and pediatric patients aged more than 12 years old with iobenguane scan–positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.

The decision was based on findings from a phase IIb trial that was conducted under the FDA's special protocol assessment. In the study, the radiopharmaceutical elicited a greater than 50% reduction in antihypertensive medication use for more than 6 months for 25% of patients with PPGL. In those receiving at least 2 therapeutic doses, this was achieved for 32% of patients.

Iobenguane I-131 is made using UltraTrace, which results in less non-radioactive MIBG during enrichment, leading to greater delivery of radiation to the tumor. The UltraTrace technology was developed by Molecular Insight Pharmaceuticals, which was later acquired by Progenics in 2013.

The novel agent was previously granted a breakthrough therapy designation for the treatment of PPGL, along with orphan drug and fast track designations. An expanded access program for iobenguane I-131 is currently available for patients with MIBG-avid malignant and/or recurrent PPGL. The program also plans to further assess safety.

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

In breast cancer, the FDA has approved the Magtrace and Sentimag Magnetic Localization System used to guide lymph node biopsies in women undergoing mastectomy. The system uses magnetic detection to identify sentinel lymph nodes for surgical removal.

The magnetic Magtrace particles are injected into the patient’s breast tissue and become trapped in the lymph nodes. The surgeon then applies the Sentimag probe to the patients’ skin near the tumor site, and detects the magnetic particles located within the sentinel lymph node. That node is then removed and tested for the presence of cancer cells.

Endomag, the system’s manufacturer, stated the device is less invasive than wire-guided localization and allows greater flexibility in scheduling for patients, surgeons, and radiologists.

Endomag submitted updated data from the open-label, multicenter, paired comparison SentimagIC trial evaluating Magtrace versus a Technetium 99-labeled sulfur colloid radioisotope/isosulfan blue dye control. The study met the primary endpoint of noninferiority for lymph node detection rate.

Endomag received FDA approval for Sentimag and the marker technology Magseed in 2016.

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

The FDA approved filgrastim-aafi, known by the trade name Nivestym, a filgrastim biosimilar, to prevent and treat adverse events associated with cancer treatment, including febrile neutropenia and severe neutropenia.

This is the second filgrastim biosimilar approved for use in the United States following the 2015 approval of EP2006.

Filgrastim-aafi is indicated to reduce the incidence and duration of these side effects in patients with nonmyeloid malignancies undergoing myelosuppressive therapy, those with acute myeloid leukemia following induction or consolidation chemotherapy, patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation, those with chronic congenital, cyclic, or idiopathic neutropenia, and patients undergoing autologous hematopoietic progenitor cell collection and treatment.

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

In acute myeloid leukemia, the FDA has approved ivosidenib, known by the trade name Tibsovo, for the treatment of adult patients with relapsed/refractory IDH1-mutant disease.

The approval was based on findings of a single-arm phase I study of 174 patients with IDH1-positive relapsed/refractory AML. Results showed that the complete remission rate was 24.7% and the CR with partial hematologic improvement rate was 8%. Moreover, the median duration of CR plus CRh was 8.2 months. Among the CR/CRh population, the median time to best response was 2.0 months.

Regarding safety, all-grade adverse events occurring in more than 20% of patients included fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, electrocardiogram QT prolonged, rash, pyrexia, cough and constipation. The most common serious AEs occurring in at least 5% of patients included differentiation syndrome, leukocytosis, and electrocardiogram QT prolonged.

The FDA label for ivosidenib includes a boxed warning regarding differentiation syndrome, warning that the condition can be fatal if not treated.

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

The FDA has granted a breakthrough therapy designation to the combination of lenvatinib and pembrolizumab for the treatment of patients with advanced and/or metastatic non–microsatellite instability high/proficient mismatch repair endometrial carcinoma who have progressed after more than 1 prior systemic therapy.

The decision was based on interim data from the phase Ib/II basket Study 111/KEYNOTE-146 trial, which were presented at the 2018 ASCO Annual Meeting. In the 53-patient endometrial cancer cohort, the objective response rate at week 24 per independent radiology review was 45.3% with the combination. The overall ORR was 47.2%, including 3 complete responses and 25 partial responses.

Moreover, the median PFS with the combination was 7.4 months. Nineteen patients had stable disease and 5 had progressive disease. The median duration of response was not estimable. Overall, 79.3% of patients had a duration of response lasting longer than 12 months.

This combination was previously granted a breakthrough therapy designation by the FDA in January 2018 for the treatment of patients with advanced and/or metastatic renal cell carcinoma.

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

In acute myeloid leukemia, the FDA has granted a breakthrough therapy designation to quizartinib for the treatment of adult patients with relapsed/refractory FLT3-ITD–positive acute myeloid leukemia.

The designation is based on data from the phase III QuANTUM-R study, in which the FLT3 inhibitor reduced the risk of disease progression or death by 24% versus salvage chemotherapy in patients with FLT3-ITD–positive relapsed/refractory AML after frontline treatment with or without hematopoietic stem cell transplantation.

At a median follow-up of 23.5 months, the median overall survival was 6.2 months with quizartinib compared with 4.7 months with salvage chemotherapy.

Data from the QuANTUM-R study confirmed the efficacy and safety of quizartinib that was observed in previous trials and showed the value of therapy targeting FLT3-ITD. It is the first trial to demonstrate improved overall survival for patients with FLT3-ITD–associated AML who are treatment resistant or who relapsed after prior therapy.

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

This week, we sat down with Dr Alexander Drilon, of Memorial Sloan Kettering Cancer Center, to discuss ongoing challenges with TRK inhibition.

That’s all for today.

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