May 9, 2018 : Episode 1

FDA Approvals in Myeloma and Thyroid Cancer, Priority Review and NDA in NSCLC, and More



FDA approvals in myeloma and thyroid cancer, a priority review designation and a new drug application submitted in non—small cell lung cancer, a complete response letter issued for a rituximab biosimilar, and an AML treatment recommended in the United Kingdom.

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

The FDA has approved daratumumab in combination with bortezomib, melphalan, and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

This decision was based on findings from the pivotal phase III ALCYONE study, in which daratumumab plus VMP demonstrated a 50% reduction in the risk of progression or death compared with VMP alone. The median progression-free survival was 18.1 months in the VMP arm and was not yet reached for those treated with the daratumumab regimen. Moreover, follow up remained ongoing for overall survival at the 16.5-month assessment.

A marketing authorization application for daratumumab plus VMP is pending in the European Union, where the VMP regimen is more commonly used. The MAA was submitted to the European Medicines Agency in November 2017.

Daratumumab continues to be explored across several clinical trials, including the phase III CASSIOPEIA study, which is looking at the anti-CD38 antibody in combination with bortezomib, thalidomide, and dexamethasone for untreated transplant-ineligible patients with multiple myeloma.


In thyroid cancer, the FDA has approved combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib for the treatment of patients with unresectable or metastatic BRAF V600E—positive anaplastic disease. This is the first FDA approved treatment for patients with this aggressive form of thyroid cancer.

The approval is based on results of an open-label trial that accrued patients with rare cancers harboring a BRAF V600E mutation. Among 23 patients evaluable for efficacy, 57% achieved a partial response and 4% reached a complete response. Among the 14 responders, 64% had no significant tumor growth for at least 6 months.

In the approval notice, the agency reported that adverse events with dabrafenib plus trametinib were similar to those observed in patients with other tumor types who received the combination.

In results that were previously published in the Journal of Clinical Oncology, nearly 7 in 10 patients with locally advanced or metastatic BRAF V600E—mutated disease responded to treatment with dabrafenib and trametinib.

The confirmed overall response rate was 69%. One patient had a complete response and 10 had partial responses. Seven patients had ongoing responses at the time of the analysis.


The FDA has granted a priority review to a supplemental biologics license application for atezolizumab for use in combination with bevacizumab, carboplatin, and paclitaxel for the first-line treatment of patients with metastatic nonsquamous non—small cell lung cancer.

The application is a based on data from the phase III IMpower150 trial, in which the atezolizumab regimen demonstrated a median progression-free survival of 8.3 months versus 6.8 months with bevacizumab and chemotherapy alone, which translated to a 38% reduction in the risk of progression or death.

The 12-month PFS rate was 37% with the atezolizumab-containing regimen and 18% with the bevacizumab plus chemotherapy regimen. The objective response rate was 64% versus 48%, respectively.

Genentech, the manufacturer of atezolizumab, reported in March 2018 that the atezolizumab regimen also significantly improved overall survival versus bevacizumab and chemotherapy alone. The company plans to present these data at an upcoming medical meeting, and the FDA is scheduled to make its decision on the application by September 5, 2018.


The FDA has issued a complete response letter to Sandoz, a division of Novartis, regarding a biologics license application for the rituximab biosimilar GP2013.

The letter indicates that the FDA has completed its review and the BLA is not ready for approval. Sandoz did not provide further details in its statement on the CRL.

In September 2017, Sandoz reported that the FDA had accepted a BLA for GP2013. The biosimilar would have been indicated for follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia, as well as for rheumatoid arthritis. In June 2017, the European Commission approved GP2013, which is known by the trade name Rixathon, to be marketed for these indications in the European Union.

Sandoz supported the application submitted to the FDA with a series of data, including results from the ASSIST-RA study in rheumatoid arthritis and the phase III confirmatory ASSIST-FL study in follicular lymphoma.

Results showed that the overall response rate was 87.1% in the GP2013-CVP arm versus 87.5% in the rituximab-CVP arm. The rate of complete response was 14.8% versus 13.4%, and the partial response rate was 72.3% and 74.1% in the GP2013-CVP arm and rituximab-CVP arms, respectively.

Moreover, the median progression-free survival and overall survival had not been reached.


The National Institute for Health and Care Excellence has authorized the use of midostaurin in combination with standard chemotherapy for the treatment of patients with newly diagnosed FLT3-positive acute myeloid leukemia.

Midostaurin is specifically recommended in the United Kingdom for use in combination with daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy. For patients who achieve a complete response after this initial treatment, NICE also recommended single-agent midostaurin maintenance therapy.

The recommendation is based on data from the phase III RATIFY trial, in which the addition of midostaurin to standard chemotherapy reduced the risk of death by 22% versus chemotherapy alone in patients with AML who harbored a FLT3 mutation.

Uncensored data showed that the median OS was 74.7 months with midostaurin versus 25.6 months with chemotherapy alone, and the 5-year OS rate for patients in the midostaurin arm was 50.9% versus 43.9% with placebo.

Moreover, median event-free survival in the midostaurin arm was 8.2 versus 3.0 months with placebo. The 5-year EFS rate with midostaurin was 27.5% versus 19.3% with placebo.


This week, we sat down with Dr John Heymach of The University of Texas MD Anderson Cancer Center to discuss personalizing therapy for patients with EGFR exon 20-mutant 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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