October 23, 2019 - Episode 1

FDA Approvals in Ovarian Cancer and for MEC Chemo, Promising Data in Lung Cancer, and More


FDA approvals in ovarian cancer and for patients receiving moderately epigenetic chemotherapy, label recommendations for breast implant manufacturers, and encouraging data in lung cancer, breast cancer, and hepatocellular carcinoma.

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

The FDA has approved niraparib for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with 3 or more prior chemotherapy regimens, and whose cancer is associated with homologous recombination deficiency-positive status.

The approval is based on results from the single-arm, phase II QUADRA study, which showed that niraparib elicited an overall response rate of 24%, which was comprised of all partial responses, in the primary efficacy population of patients who were HRD positive and who received at least 3 prior lines of therapy. The estimated median duration of response was 8.3 months.

HRD is defined by either a deleterious or suspected deleterious BRCA mutation, or genomic instability in patients with disease progression greater than or equal to 6 months after response to the last platinum-based chemotherapy.

Data also showed that in patients with BRCA-mutant ovarian cancer, the ORR was 39% in patients with platinum-sensitive disease, 29% in those with platinum-resistant disease, and 19% in patients with platinum-refractory disease. For those with platinum-sensitive, genomic instability score-positive disease, without BRCA mutations, the investigator-assessed ORR was 20%.

The FDA simultaneously approved the companion diagnostic myChoice® CDx for use by healthcare professionals to identify patients with advanced ovarian cancer who are candidates for niraparib in the late-line treatment setting.


The FDA has expanded the approval of aprepitant injectable emulsion for intravenous use to include the 130-mg single-dose regimen for patients who are receiving moderately epigenetic chemotherapy.

Aprepitant is a polysorbate 80-free, IV formulation of an NK1 receptor antagonist, which is designed to significantly reduce chemotherapy-induced nausea and vomiting in both the acute and delayed phases following chemotherapy.

The label expansion standardizes the aprepitant 130 mg single-dose regimen for patients receiving highly emetogenic cancer chemotherapy and/or MEC as an injection over 2 minutes or an infusion over 30 minutes, which eases the dosing and administration, and eliminates the need to take oral aprepitant on days 2 and 3 following MEC administration.

The expanded approval also builds on the prior label expansion that introduced the 2-minute IV push, which enables physicians to utilize the operational advantages of this administrative method and helps reduce total patient time spent at the infusion site.


The FDA has issued a draft guidance to propose labeling recommendations to breast implant manufacturers in an effort to help patients understand the benefits and risks of these devices. In the proposed labeling recommendations, the agency recommended that a boxed warning be included in the labeling for breast implants, with information including that these implants are not lifetime devices and the risk of developing complications increase the longer a patient has the implant. Therefore, additional surgery may be required to address such complications.

The draft guidance also includes measures to help ensure women have access to information on the benefits and risks of breast implants, including recommendations that manufacturers incorporate a patient decision checklist in the device's labeling, and updated guidelines for patient screening for ruptured devices.

The FDA also stated that implants have been associated with the risk of developing breast implant-associated anaplastic large cell lymphoma and may be associated with systemic symptoms, such as fatigue or joint pain. In 2017, the FDA released a warning advisory that breast implants may increase an individual's risk of developing ALCL.


In non-small cell lung cancer, the first-line combination of nivolumab plus low-dose ipilimumab given concomitantly with 2 cycles of chemotherapy showed superior overall survival versus up to 4 cycles of chemotherapy alone followed by optional maintenance treatment for patients with advanced disease, meeting the primary endpoint of the phase III CheckMate-9LA trial.

At the prespecified interim analysis, the safety profile of the immunotherapy/chemotherapy combination was also found to be consistent with prior results of each agent alone.

Bristol-Myers Squibb, the developer of the PD-1 and CTLA-4 inhibitors, stated in a press release that it will complete a full evaluation of the phase III data. The findings will also be presented at an upcoming medical meeting and will be discussed with regulatory authorities.


In findings from the phase II HER2CLIMB trial, tucatinib combined with trastuzumab and capecitabine improved overall survival and progression-free survival compared with trastuzumab and capecitabine alone in heavily pretreated patients with locally advanced unresectable or metastatic HER2-positive breast cancer.

Specifically, results showed that that the addition of the small molecule TKI to trastuzumab and capecitabine led to a 34% reduction in the risk of death over trastuzumab/capecitabine alone.

Additionally, the tucatinib triplet improved PFS over trastuzumab/capecitabine alone, demonstrating a 46% reduction in the risk of disease progression or death. The tucatinib arm was also associated with a 52% reduction in the risk of disease progression or death in patients who had brain metastases at baseline. Adding tucatinib to trastuzumab and capecitabine was found to be well tolerated with a manageable safety profile.

Seattle Genetics, the developer of tucatinib, stated in a press release that it plans to unblind the trial and offer tucatinib to patients on the control arm. Moreover, a new drug application will be submitted to the FDA in the first quarter of 2020.


Also in HER2-positive breast cancer, the combination of margetuximab and chemotherapy induced a 1.8-month median overall survival increase in patients with pretreated HER2-positive metastatic breast cancer versus trastuzumab and chemotherapy, according to topline findings of a second prespecified interim OS analysis of the phase III SOPHIA trial.

The updated results showed that in the intent-to-treat population, the median OS in patients treated with margetuximab and chemotherapy was 21.6 months compared with 19.8 months for those who had trastuzumab/chemotherapy.

A prespecified exploratory objective was to evaluate the effect of CD16A allelic variation on margetuximab activity. In the estimated 85% of patients carrying a CD16A 158F allele, the median OS was 23.7 months in the margetuximab arm versus 19.4 months in the trastuzumab arm.

However, in the estimated 15% of those who were homozygous for the CD16A 158V allele, the trastuzumab regimen performed better than those on margetuximab/chemotherapy.

Margetuximab plus chemotherapy also showed a safety profile that was generally comparable with trastuzumab plus chemotherapy and was also consistent with previously reported data.


In hepatocellular carcinoma, atezolizumab combined with bevacizumab showed statistically significant and clinically meaningful improvements in both progression-free and overall survival versus sorafenib in patients with unresectable disease who have not received prior therapy, meeting the coprimary endpoints of the IMbrave150 trial.

The safety findings for the combination were consistent with the known profiles of each agent alone, and no new safety signals were identified.

These data will be submitted to regulatory authorities and will be presented at an upcoming medical meeting.

In July 2018, the FDA granted a breakthrough therapy designation to the combination of atezolizumab and bevacizumab as a first-line treatment for patients with advanced or metastatic HCC based on an ongoing phase Ib trial, in which results from independent reviewers determined that atezolizumab plus bevacizumab elicited an objective response rate of 65% among 23 evaluable patients.


This week, we sat down with Dr David S. Hong, of The University of Texas MD Anderson Cancer Center, to discuss how he envisions the use of TRK inhibitors in clinical practice.

That's all for today.

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