RECENT APPROVALS: Pembrolizumab (Keytruda) was approved by the FDA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1. The following indications for pembrolizumab were added for metastatic NSCLC: (1) tumors that have high PD-L1 expression (>50%), with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC, and (2) tumors that express any degree of PD-L1, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab. This is the first FDA approval of a checkpoint inhibitor for first-line treatment of lung cancer. This approval also expands the indication in second-line treatment of lung cancer to include all patients with PD-L1-expressing NSCLC. Both approvals are based on published phase III randomized trials. (As of October 24, 2016.)
Atezolizumab (Tecentriq) was approved by the FDA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose disease progressed during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab. This approval is based on results from the randomized phase III OAK and phase II POPLAR studies. The phase III trial showed a significant improvement in overall survival in patients with locally advanced or metastatic NSCLC, regardless of PD-L1 status, after previous cytotoxic therapy. (As of October 18, 2016.)
The indication labeling for erlotinib (Tarceva) was modified by the FDA to limit the its use to patients with non-small cell lung cancer (NSCLC) whose tumors have specific epidermal growth factorreceptor activating mutations. The labeling change applies to patients with NSCLC receiving maintenance or second- or greater-line treatment. These indications will be limited to patients whose tumors have EGFR exon 19 deletions or exon 21 L858R substitution mutations. The first-line indication previously has already been limited to patients with EGFR exon 19 deletions or exon 21 substitution mutations. Its prior approval, independent of mutation status, in the second- and third-line setting after failure of one or two chemotherapy regimens has been rescinded. (As of October 18, 2016.)
Nivolumab (Opdivo) was approved by the Scottish Medicines Consortium (SMC) as treatment for locally advanced or metastatic non-squamous NSCLC, where the disease has progressed after prior chemotherapy. This recommendation means that Scottish patients on the National Health Service will become the first in the United Kingdom to be offered treatment with nivolumab. SMC previously (July 2016) approved nivolumab for locally advanced or metastatic squamous NSCLC after prior chemotherapy. (As of October 10, 2016.)
Osimertinib (Tagrisso) was recommended in draft guidance by National Institute for Health and Care Excellence (NICE) as a second-line option for patients with advanced NSCLC that is EGFR T790M-positive. The final draft guidance issued by NICE says osimertinib should be made available through the Cancer Drugs Fund (CDF), after a financial agreement was reached with AstraZeneca. It is the first drug to be approved under the updated CDF. (As of October 4, 2016.)
A label extension was approved by the FDA for the cobas® EGFR Mutation Test v2 with plasma samples as a companion diagnostic for second-line osimertinib (Tagrisso) therapy in the treatment of T790M positive advanced NSCLC. Previously, the FDA granted approval of the cobas® EGFR Mutation Test v2 for use with plasma or tissue DNA as a companion diagnostic for erlotinib (Tarceva) as first-line therapy for EGFR mutation-positive advanced NSCLC. The test is the only FDA-approved companion diagnostic for the detection of the EGFR mutations in plasma DNA. (As of September 9, 2016.)
Crizotinib (Xalkori) was approved by the European Commission for the treatment of ROS1-positive advanced NSCLC. In the European Union (EU), as in China, Japan, the US, and numerous other countries, crizotinib is also indicated for treatment of adults with ALK-positive advanced NSCLC. Crizotinib has previously been approved in the USA for first-line treatment of ROS1-positive advanced NSCLC. (As of August 31, 2016.)
Pemetrexed (Alimta) was approved by the NICE for the maintenance treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) after four cycles of pemetrexed and cisplatin induction therapy. Pemetrexed was already recommended by NICE as maintenance treatment for those who had received a platinum doublet chemotherapy not containing pemetrexed and for first-line therapy in combination with cisplatin. (As of August 24, 2016.)
Crizotinib (Xalkori) was approved by NICE as a first-line treatment for anaplastic lymphoma kinase (ALK)-positive advanced NSCLC. Previously, crizotinib was only recommended for use after standard chemotherapy (as of September 26, 2016). The Scottish Medicines Consortium (SMC) has also recommended crizotinib for use in the first-line, treatment-naive setting for ALK positive NSCLC. (As of August 23, 2016.)
BREAKTHROUGH THERAPY DESIGNATION:
Alectinib (Alecensa) was granted breakthrough therapy designation by the FDA on October 4, 2016 for first-line treatment of individuals with ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor. This second breakthrough therapy designation was based on the results of the open-label, randomized phase III J-ALEX study, which was presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting in June and which showed a significant improvement in response rate and PFS compared with “standard” crizotinib. Alectinib received its first FDA breakthrough therapy designation in June 2013 for people with ALKpositive NSCLC whose disease had progressed on treatment with or were intolerant to crizotinib and was formally approved for this purpose on December 11, 2015.
