Dr. Brahmer on Treatment Following Progression on First-line Immunotherapy in NSCLC

Julie Renee Brahmer, MD, co-director, the Upper Aerodigestive Department, the Bloomberg-Kimmel Institute for Cancer Immunotherapy, professor of Oncology, Johns Hopkins Medicine, discusses clinical trials investigating treatment options for patients with non–small cell lung cancer (NSCLC) following progression after first-line immunotherapy.

Although there are limited options after first-line progression, Brahmer notes that there are some data emerging from the phase 3 EMPOWER-Lung 1 trial (NCT03409614), which evaluated agent cemiplimab-rwlc (Libtayo) monotherapy vs standard-of-care chemotherapy as frontline treatment in patients with NSCLC with a PD-L1 expression of at least 50%. At the time of progression on cemiplimab, patients were allowed add chemotherapy to cemiplimab, and this strategy led to responses and long-term disease control, Brahmer notes.

Those data from EMPOWER-Lung 1 were encouraging; however, Brahmer explains that data from additional ongoing trials could also shed light on the optimal sequencing of therapies for patients with PD-L1–positive disease, Brahmer notes. A phase 3 trial (NCT03793179) is currently examining pembrolizumab (Keytruda), followed by pemetrexed plus carboplatin with or without pembrolizumab after disease progression, vs the combination of pembrolizumab, pemetrexed, and carboplatin as first-line therapy before moving on to a different therapy at the time of progression.

There are additional studies looking at patients who are immunotherapy refractory following disease progression. The phase 2 Lung-MAP S1800A trial (NCT03971474) evaluated the addition of ramucirumab (Cyramza), which is an anti-VEGF therapy, to pembrolizumab, in patients with NSCLC previously treated with immunotherapy, and the combination produced an improvement in overall survival, Brahmer continues.

Pembrolizumab plus ramucirumab will be investigated further investigation in the phase 3 Pragmatica-Lung trial (NCT05633602) in patients who are immune-oncology refractory from the first-line treatment setting and randomly assigning them to either pembrolizumab plus ramucirumab (Cyramza) or docetaxel alone, Brahmer expands. This trial will help provide more context for treatment decisions in the immunotherapy refractory setting. Currently, in the refractory setting, if a patient received immunotherapy with chemotherapy up front, the standard of care is docetaxel with or without ramucirumab, Brahmer concludes.