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Lung Cancer

Moving PD-1 or PD-L1 inhibitors to an early line of therapy, immediately after chemoradiation, has improved survival for patients with unresectable, stage III non–small-cell lung cancer (NSCLC).
Tumor expression of PD-L1 has consistently predicted ­response and survival outcomes in non–small-cell lung cancer (NSCLC), whereas the role of PD-L1 in immune cells is unclear, said Edward B. Garon, MD, Director, Thoracic Oncology Program, David Geffen School of Medicine, University of California, Los Angeles, at the 2019 ASCO-SITC Clinical Immuno-Oncology Symposium.
For the second time this month, the FDA has given an approval to Genentech’s PD-L1 inhibitor, Tecentriq.
Although many new treatments, including targeted therapies and immunotherapies, have recently become available for patients with non–small-cell lung cancer, those with small-cell lung cancer have not seen new treatment options in the past 2 decades. But this is about to change.

A burning question is whether immunotherapy combinations will further improve outcomes compared with checkpoint inhibitor therapy alone—and if so, which combinations will rise to the top.

The FDA accelerated the approval of brigatinib (Alunbrig), a new generation of oral ALK inhibitor, for the treatment of patients with ALK-positive metastatic NSCLC who do not tolerate or have had an inadequate response to crizotinib..

A post hoc analysis of the phase 2 ALTA trial showed longer overall survival in crizotinib-refractory patients with advanced ALK-positive NSCLC who continued brigatinib versus discontinuing it after disease progression.
In treatment-naïve patients with NSCLC and high tumor mutation burden—regardless of PD-L1 expression—the combination of nivolumab plus ipilimumab showed superior PFS versus chemotherapy in the phase 3 CheckMate-227 trial.
Amid the changing landscape of treatments for ALK-positive NSCLC, sequencing of ALK inhibitors grows more complex and will require an assessment of individual patient’s tumor characteristics.
Seribantumab (MM-121), a drug under investigation in the phase 2 SHERLOC trial for the treatment of heregulin-positive NSCLC, was granted orphan drug designation from the FDA.
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