FDA Approval in HER2+ Breast Cancer, Priority Review in NSCLC, and More

Today-

An FDA approval in HER2-positive breast cancer, a priority review designation in lung cancer, a breakthrough therapy designation in head and neck cancer, applications accepted in ovarian cancer and breast cancer, and an ODAC decision in lung cancer.

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

The FDA has approved a supplemental new drug application for neratinib in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received at least 2 prior anti—HER2-based regimens in the metastatic setting.

The approval is based on findings from the phase III NALA trial, which showed that the combination of neratinib and capecitabine reduced the risk of disease progression or death by 24% compared with lapatinib plus capecitabine.

Moreover, the objective responsive rate was 32.8% for the neratinib arm and 26.7% for the lapatinib arm, respectively. The median duration of response was 8.5 months versus 5.6 months, respectively.

Neratinib was initially approved for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy.

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In non—small cell lung cancer, the FDA has granted a priority review designation to a supplemental new drug application for brigatinib for the first-line treatment of patients with ALK-positive metastatic disease, as detected by an FDA-approved test.

The application is based on the phase III ALTA-1L trial, in which treatment with brigatinib demonstrated a 57% reduction in the risk of disease progression or death versus crizotinib in patients with advanced ALK-positive NSCLC who had not received a prior ALK inhibitor.

The 2-year investigator-assessed results also showed that brigatinib led to a 76% reduction in the risk of disease progression or death in newly diagnosed patients who had brain metastases at the time of enrollment.

Moreover, with the 2-year follow-up data, the trial’s results were evaluated and reported by both study investigators and a blinded independent review committee. At the data cutoff for the second interim analysis, results showed that by BIRC assessment, there was a 51% reduction in the risk of disease progression or death with brigatinib over crizotinib.

The FDA is expected to make a decision on the sNDA by June 23, 2020.

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The FDA has granted a breakthrough therapy designation to Debio 1143 for the treatment of patients with previously untreated, unresectable, locally advanced squamous cell carcinoma of the head and neck in combination with standard cisplatin-based concomitant fractionation chemoradiation therapy.

The designation is based on results from a phase I/II trial, in which Debio 1143 plus CRT demonstrated a 20.8% improvement in investigator-assessed 18-month locoregional control rate compared with CRT/placebo. After a 2-year follow-up period, progression-free survival also favored the Debio 1143 arm.

Debio 1143 was also found to have a predictable and manageable safety profile and did not compromise the full delivery of standard CRT.

Debio 1143 is a potential first-in-class oral antagonist of inhibitor of apoptosis protein that sensitizes tumor cells to chemoradiation by promoting programmed cell death and fostering antitumor immunity.

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In ovarian cancer, the FDA accepted a supplemental new drug application for niraparib for use as a frontline maintenance treatment for women with advanced ovarian cancer who responded to platinum-based chemotherapy, regardless of biomarker status.

The application is based on findings from the phase III PRIMA study, in which frontline maintenance therapy with niraparib improved median progression-free survival by 5.6 months compared with placebo for patients with newly diagnosed, advanced ovarian cancer who responded to platinum-based chemotherapy.

In the overall study population, the median PFS in the niraparib arm was 13.8 months versus 8.2 months in the placebo group, leading to a 38% reduction in the risk of progression or death with the addition of the PARP inhibitor. In patients with tumors that tested positive for homologous recombination deficiency, the median PFS was 21.9 months with niraparib versus 10.4 months for placebo.

Shortly after the FDA’s acceptance, the European Medicines Agency validated a Type II Variation for niraparib as a first-line maintenance treatment for patients with advanced ovarian cancer who have responded to platinum-based chemotherapy, regardless of biomarker status.

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In breast cancer, the FDA accepted a biologics license application for a fixed-dose combination of pertuzumab and trastuzumab with hyaluronidase, administered by subcutaneous injection in combination with intravenous chemotherapy, for the treatment of eligible patients with HER2-positive disease.

The application is based on findings from the phase III FeDeriCa study, in which the subcutaneous fixed-dose combination of pertuzumab and trastuzumab demonstrated noninferiority to intravenous formulations of the 2 drugs with respect to pharmacokinetics, clinical activity, and safety.

The total pathologic complete response in the breast and axilla and safety also were similar between the 2 treatment regimens.

The safety analysis showed that incidences of the most common adverse events were similar between both arms, including alopecia, nausea, diarrhea, anemia, and asthenia.

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The FDA's Oncologic Drugs Advisory Committee voted 6 to 5 in favor of intravenous ramucirumab injection for use in combination with erlotinib as a frontline treatment for patients with metastatic non—small cell lung cancer whose tumors harbor EGFR exon 19 deletions or exon 21 substitution mutations.

The FDA scheduled the Oncologic Drugs Advisory Committee hearing to discuss data supporting a supplemental biologics license application for the combination in this setting, which was based on findings from the phase III RELAY trial.

In the study, results showed that the addition of ramucirumab to erlotinib led to a 41% reduction in the risk of disease progression or death compared with erlotinib alone in the first-line treatment of patients with EGFR-mutated NSCLC.

The committee sought to discuss whether the risk-benefit profile of ramucirumab plus erlotinib could be adequately assessed without overall survival data, and whether the improvement seen in PFS is clinically meaningful in the context of additive toxicity.

In the combination arm in RELAY, the rate of grade 3 or higher adverse events was 72% compared with 54% for erlotinib alone, and the rate of serious AEs was 29% and 21%, respectively.

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This week, we sat down Richard S. Finn, MD, University of California Los Angeles, discusses the use of immunotherapy in patients with unresectable hepatocellular carcinoma.

That’s all for today.

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