September 4, 2019 : Episode 1

FDA Delays Decision in Lung Cancer, Orphan Drug Status in Breast Cancer, and More



A delay on a regulatory decision in lung cancer, an orphan drug status in breast cancer, disappointing findings in glioblastoma multiforme, a European approval in renal cell carcinoma, and a Chinese approval in lung cancer.

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

The FDA has extended the review period for a supplemental biologics license application for atezolizumab for use in combination with carboplatin and nab-paclitaxel as a first-line treatment for patients with metastatic nonsquamous non—small cell lung cancer who do not have EGFR or ALK aberrations.

The extension will allow ample time for the FDA to review additional information it requested for the application. The new action date for the sBLA is December 2, 2019.

In January 2019, Roche, the manufacturer of atezolizumab, reported that the FDA had granted a priority review to the sBLA based on findings from the phase III IMpower130 trial. Results of the study demonstrated a statistically significant improvement in both progression-free and overall survival with the atezolizumab triplet compared with chemotherapy alone in patients with stage IV nonsquamous NSCLC.

Data from the interim analysis showed that the atezolizumab arm was superior in OS in the intent-to-treat-wild-type population. The median OS was 18.6 months versus 13.9 months with carboplatin/nab-paclitaxel alone. Moreover, the 1- and 2-year OS rates with atezolizumab were 63.1% and 39.6% versus 55.5% and 30.0% in the carboplatin/nab-paclitaxel arm.


In breast cancer, the FDA has granted an orphan drug designation to neratinib for the treatment of patients who have brain metastases.

Prior data have demonstrated the activity of the small-molecule TKI in combination with capecitabine in patients with HER2-positive breast cancer who also have brain metastases. For example, results of the phase III NALA study showed that fewer patients required intervention for central nervous system metastases with neratinib and capecitabine versus lapatinib/capecitabine.

At 54 months, the cumulative incidence for intervention for CNS metastases was 22.8% versus 29.2% for the neratinib and capecitabine arms, respectively.

Moreover, additional study cohorts from the phase II TBCRC 022 trial showcased promising results with the combination of neratinib and capecitabine in patients with HER2-positive breast cancer and CNS metastases.

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


The combination of nivolumab plus standard temozolomide and radiation therapy did not show a statistically significant improvement in progression-free survival versus temozolomide/radiation therapy alone in patients with newly diagnosed glioblastoma multiforme that is MGMT-methylated, missing one of the primary endpoints of the phase III CheckMate-548 trial.

A data monitoring committee did recommend, however, that the trial should continue as planned to allow overall survival, the other primary endpoint, to mature. Bristol-Myers Squibb, the developer of the PD-1 inhibitor nivolumab, stated in a press release that it remains blinded to all study data.

Disappointing topline findings for the phase III CheckMate-498 trial were previously announced in May 2019, which evaluated nivolumab plus radiation therapy versus temozolomide in patients with MGMT-unmethylated GBM.

In this multicenter study, results showed that the nivolumab regimen did not improve OS over temozolomide, missing the coprimary endpoint.


In renal cell carcinoma, the European Commission has approved the combination of pembrolizumab and axitinib for the frontline treatment of patients with advanced disease. The

approval is based on findings from the phase III KEYNOTE-426 trial, in which the combination led to a 47% reduction in the risk of death versus sunitinib in this patient population. The pembrolizumab/axitinib combination also showed an improvement in both progression-free survival and objective response rate versus sunitinib.

Additionally, at a median follow-up of 12.8 months, the median OS was not reached in either arm. The median PFS was 15.1 months for pembrolizumab/axitinib and 11.1 months with sunitinib. With the combination, there was also a 31% reduction in the risk of disease progression.

With the approval, the combination is now available for use in all 28 European Union member states, as well as Iceland, Lichtenstein, and Norway. The regimen was also approved by the FDA in April 2019.


In non—small cell lung cancer, China’s National Medical Products Administration has approved osimertinib for the frontline treatment of adult patients with locally advanced or metastatic non–small cell lung cancer whose tumors harbor EGFR exon 19 deletions or exon 21 (L858R) substitutions.

The approval is based on data from the phase III FLAURA trial, in which frontline osimertinib reduced the risk of progression or death by 54% versus standard TKI therapy with erlotinib or gefitinib. In the double-blind study, the median progression-free survival was 10.2 months for standard therapy and 18.9 months with osimertinib.

Additionally, the PFS benefit with osimertinib extended across all prespecified subgroups.

The objective response rate with osimertinib was 77% compared with 69% for erlotinib and gefitinib. The median duration of response with osimertinib was 17.6 months versus 9.6 months in the comparator arm.

Osimertinib was previously approved in the United States and Europe for the frontline treatment of patients with EGFR-positive NSCLC.


This week, we sat down with Dr Hussein Tawbi, of The University of Texas MD Anderson Cancer Center, to discuss BRAF and MEK in melanoma.

That’s all for today.

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

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