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FDA Approval in Myeloma, Label Update in HER2+ Breast Cancer, Breakthrough Status in Prostate Cancer, and More

Gina Columbus
Published: Saturday, Oct 12, 2019



Today-

An FDA approval in multiple myeloma, a label update in breast cancer, a breakthrough therapy designation in prostate cancer, research grants awarded in rare diseases, and two trials in pediatric acute lymphoblastic leukemia stopped early due to benefit.

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

The FDA has approved daratumumab in combination with bortezomib, thalidomide, and dexamethasone, known as the D-VTd regimen, for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant.

The approval is based on results from part 1 of the phase III CASSIOPEIA study, in which the stringent complete response rate at post-consolidation therapy was 29% in patients who received the D-VTd regimen versus 20% in those who received VTd alone.

Additional data showed that the overall response rate post-consolidation therapy was 93% with D-VTd and 90% with VTd; the complete response or higher rates were 39% and 26%, respectively. The complete response rates were 10% and 6%, and the very good partial response rates were 45% and 52%, respectively. The partial response rates were 9% and 12% for the D-VTd and VTd-alone arms, respectively. Responses were also found to deepen over time.

At a median follow-up of 18.8 months, the median PFS had not yet been reached in either arm, and the daratumumab regimen showed a 53% reduction in the risk of disease progression or death.

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

In breast cancer, the FDA has approved a labeling supplement for neratinib for the extended adjuvant treatment of patients with HER2-positive early-stage disease.

The supplement includes safety information based on interim results of the phase II CONTROL trial, in which the addition of prophylactic treatment with loperamide plus budesonide reduced the discontinuation rate of neratinib due to associated diarrhea to 11% versus 18% for those who received loperamide alone.

Results showed that in the loperamide/budesonide cohort, the incidence of grade 3 diarrhea was 28.1% compared with 32% in those treated with loperamide alone. More findings that were presented at the 2019 ASCO Annual Meeting showed that the addition of budesonide or colestipol to loperamide reduces the rate of neratinib discontinuation due to diarrhea, which permits patients to receive the full 1-year dose of neratinib.

The FDA initially approved neratinib in July 2017 for the extended adjuvant treatment of adult patients with early-stage, HER2-positive breast cancer following adjuvant trastuzumab-based therapy.

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

The FDA has granted a breakthrough therapy designation to niraparib for the treatment of patients with BRCA1/2–mutant metastatic castration-resistant prostate cancer who have previously received taxane-based chemotherapy and an androgen receptor inhibitor.

The decision is based on data from the phase II GALAHAD study, in which the PARP inhibitor demonstrated a 41% objective response rate and a 63% composite response rate in patients with mCRPC who have BRCA biallelic DNA-repair gene defects.

Results also showed that the 50% prostate-specific antigen response rate was 50%, and the circulating tumor cell conversion rate was 47% in this subgroup. The median duration of objective response was 5.6 months and responses were ongoing in 7 of 12 patients. Moreover, the median radiographic progression-free survival and overall survival were 8.2 and 12.6 months, respectively.

The composite response rates in measurable and nonmeasurable patients with BRCA biallelic DNA repair-gene defects, or “DRD,” was 66% and 59%, respectively. In those with non-BRCA biallelic DRD, the ORR was 9% and the composite response rate was 17%.

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

The FDA has awarded 12 new research grants that together total more than $15 million, to enhance the development of medical products for patients with rare diseases.

Eighty-nine clinical trial grant applications were reviewed by more than 100 rare disease experts, which also includes those of academia. The FDA added in their statement that 75% of the new awards fund trials that are enrolling children.

Some of the grants include research supporting rare malignancies, including: the small molecule PTC596 for the treatment of patients with diffuse intrinsic pontine glioma and high-grade gliomas; quercetin chemoprevention for the treatment of squamous cell carcinoma in patients with Fanconi Anemia; the cisplatin transmucosal system PRV111 as a potential treatment for patients with oral cancer; temozolomide for the treatment of patients with advanced or metastatic gastrointestinal stromal tumor, specifically those who have SDH mutations or deficiencies; oncolytic engineered herpes simplex virus therapy for the treatment of pediatric malignant cerebellar brain tumors; and imipridone as a potential therapy for patients with acute myeloid leukemia.

The grants are awarded through the Congress-funded Orphan Products Clinical Trials Grants Program, which is designed to encourage clinical development of drugs, biologics, medical devices, and medical foods for the treatment of patients with rare diseases. The grants are also planned to contribute to marketing approval of products for these rare diseases or provide the necessary clinical data that are required for development of such products.

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

Two studies evaluating blinatumomab compared with chemotherapy in pediatric patients with acute lymphoblastic leukemia were stopped early due to treatment benefit with the bispecific T-cell engager.

In the phase III Study 20120215 trial, blinatumomab improved event-free survival versus conventional consolidation chemotherapy in pediatric patients with high-risk, B-cell ALL at first relapse. Due to these encouraging data, enrollment was terminated early in the blinatumomab arm based on a recommendation from an independent data monitoring committee. Follow-up will continue as prescribed per protocol.

The randomized, phase III AALL1331 study showed that blinatumomab showed a trend toward improvement in disease-free survival and overall survival, as well as lower toxicity and better minimal residual disease clearance compared with chemotherapy in pediatric patients with B-cell ALL at first relapse. Based on the data-monitoring committee, the intermediate- and high-risk arms were closed for accrual.

In the AALL1331 low-risk group, the COG data-monitoring committee recommended that this arm should continue to enroll and randomize patients until the enrollment goals are reached.

Blinatumomab is currently indicated for the treatment of adult and pediatric patients with relapsed/refractory B-cell precursor ALL, and for adult and pediatric patients with B-cell precursor ALL in first or second complete remission with MRD at least 0.1%.

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

This week, we sat down with Dr Ian Flinn, of Sarah Cannon Research Institute, to discuss PI3K inhibitors in the management of CLL.

That’s all for today.

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

An FDA approval in multiple myeloma, a label update in breast cancer, a breakthrough therapy designation in prostate cancer, research grants awarded in rare diseases, and two trials in pediatric acute lymphoblastic leukemia stopped early due to benefit.

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

The FDA has approved daratumumab in combination with bortezomib, thalidomide, and dexamethasone, known as the D-VTd regimen, for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant.

The approval is based on results from part 1 of the phase III CASSIOPEIA study, in which the stringent complete response rate at post-consolidation therapy was 29% in patients who received the D-VTd regimen versus 20% in those who received VTd alone.

Additional data showed that the overall response rate post-consolidation therapy was 93% with D-VTd and 90% with VTd; the complete response or higher rates were 39% and 26%, respectively. The complete response rates were 10% and 6%, and the very good partial response rates were 45% and 52%, respectively. The partial response rates were 9% and 12% for the D-VTd and VTd-alone arms, respectively. Responses were also found to deepen over time.

At a median follow-up of 18.8 months, the median PFS had not yet been reached in either arm, and the daratumumab regimen showed a 53% reduction in the risk of disease progression or death.

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

In breast cancer, the FDA has approved a labeling supplement for neratinib for the extended adjuvant treatment of patients with HER2-positive early-stage disease.

The supplement includes safety information based on interim results of the phase II CONTROL trial, in which the addition of prophylactic treatment with loperamide plus budesonide reduced the discontinuation rate of neratinib due to associated diarrhea to 11% versus 18% for those who received loperamide alone.

Results showed that in the loperamide/budesonide cohort, the incidence of grade 3 diarrhea was 28.1% compared with 32% in those treated with loperamide alone. More findings that were presented at the 2019 ASCO Annual Meeting showed that the addition of budesonide or colestipol to loperamide reduces the rate of neratinib discontinuation due to diarrhea, which permits patients to receive the full 1-year dose of neratinib.

The FDA initially approved neratinib in July 2017 for the extended adjuvant treatment of adult patients with early-stage, HER2-positive breast cancer following adjuvant trastuzumab-based therapy.

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

The FDA has granted a breakthrough therapy designation to niraparib for the treatment of patients with BRCA1/2–mutant metastatic castration-resistant prostate cancer who have previously received taxane-based chemotherapy and an androgen receptor inhibitor.

The decision is based on data from the phase II GALAHAD study, in which the PARP inhibitor demonstrated a 41% objective response rate and a 63% composite response rate in patients with mCRPC who have BRCA biallelic DNA-repair gene defects.

Results also showed that the 50% prostate-specific antigen response rate was 50%, and the circulating tumor cell conversion rate was 47% in this subgroup. The median duration of objective response was 5.6 months and responses were ongoing in 7 of 12 patients. Moreover, the median radiographic progression-free survival and overall survival were 8.2 and 12.6 months, respectively.

The composite response rates in measurable and nonmeasurable patients with BRCA biallelic DNA repair-gene defects, or “DRD,” was 66% and 59%, respectively. In those with non-BRCA biallelic DRD, the ORR was 9% and the composite response rate was 17%.

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

The FDA has awarded 12 new research grants that together total more than $15 million, to enhance the development of medical products for patients with rare diseases.

Eighty-nine clinical trial grant applications were reviewed by more than 100 rare disease experts, which also includes those of academia. The FDA added in their statement that 75% of the new awards fund trials that are enrolling children.

Some of the grants include research supporting rare malignancies, including: the small molecule PTC596 for the treatment of patients with diffuse intrinsic pontine glioma and high-grade gliomas; quercetin chemoprevention for the treatment of squamous cell carcinoma in patients with Fanconi Anemia; the cisplatin transmucosal system PRV111 as a potential treatment for patients with oral cancer; temozolomide for the treatment of patients with advanced or metastatic gastrointestinal stromal tumor, specifically those who have SDH mutations or deficiencies; oncolytic engineered herpes simplex virus therapy for the treatment of pediatric malignant cerebellar brain tumors; and imipridone as a potential therapy for patients with acute myeloid leukemia.

The grants are awarded through the Congress-funded Orphan Products Clinical Trials Grants Program, which is designed to encourage clinical development of drugs, biologics, medical devices, and medical foods for the treatment of patients with rare diseases. The grants are also planned to contribute to marketing approval of products for these rare diseases or provide the necessary clinical data that are required for development of such products.

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

Two studies evaluating blinatumomab compared with chemotherapy in pediatric patients with acute lymphoblastic leukemia were stopped early due to treatment benefit with the bispecific T-cell engager.

In the phase III Study 20120215 trial, blinatumomab improved event-free survival versus conventional consolidation chemotherapy in pediatric patients with high-risk, B-cell ALL at first relapse. Due to these encouraging data, enrollment was terminated early in the blinatumomab arm based on a recommendation from an independent data monitoring committee. Follow-up will continue as prescribed per protocol.

The randomized, phase III AALL1331 study showed that blinatumomab showed a trend toward improvement in disease-free survival and overall survival, as well as lower toxicity and better minimal residual disease clearance compared with chemotherapy in pediatric patients with B-cell ALL at first relapse. Based on the data-monitoring committee, the intermediate- and high-risk arms were closed for accrual.

In the AALL1331 low-risk group, the COG data-monitoring committee recommended that this arm should continue to enroll and randomize patients until the enrollment goals are reached.

Blinatumomab is currently indicated for the treatment of adult and pediatric patients with relapsed/refractory B-cell precursor ALL, and for adult and pediatric patients with B-cell precursor ALL in first or second complete remission with MRD at least 0.1%.

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

This week, we sat down with Dr Ian Flinn, of Sarah Cannon Research Institute, to discuss PI3K inhibitors in the management of CLL.

That’s all for today.

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