Julie R. Brahmer, MD
Immunotherapy advances in the treatment paradigm for patients with metastatic non–small cell lung cancer (NSCLC) could eventually lead to a cure for this disease, said Julie R. Brahmer, MD.
“Never before have we had these type of treatment choices for our patients,” explained Brahmer, associate professor of Oncology, co-director of the Upper Aerodigestive Department, Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Medicine. “Life is changing for them. Certainly, we have a further way to go to the point of curing patients with stage IV disease, but I hope some of these studies may open that avenue for patients.”
Immunotherapy and chemotherapy combinations continue to move the needle forward. In August 2018, the FDA granted a full approval to frontline pembrolizumab (Keytruda) in combination with standard chemotherapy for patients with metastatic nonsquamous NSCLC without EGFR
mutations, based on data from the phase III KEYNOTE-189 trial. An accelerated approval was granted in May 2017.
Findings showed a 51% reduction in the risk of death with the addition of pembrolizumab to pemetrexed and either cisplatin or carboplatin in the first-line setting. The median overall survival (OS) had not been met in the pembrolizumab arm compared with 11.3 months (95% CI, 8.7-15.1) in the chemotherapy-alone arm. The median progression-free survival (PFS) was 8.8 months (95% CI, 7.6-9.2) and 4.9 months (95% CI, 4.7-5.5) in the immunotherapy and control arms, respectively (HR, 0.52; 95% CI, 0.43-0.64; P
Moreover, the IMpower150 trial exploring the 4-drug regimen of atezolizumab (Tecentriq), bevacizumab (Avastin), carboplatin, and paclitaxel is showing promise in patients with advanced wild-type nonsquamous NSCLC. Brahmer noted that this trial did not exclude patients with EGFR
mutations, suggesting that this approach could be a possibility for these populations as well.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Brahmer provided an overview of the landscape of metastatic NSCLC, specifically addressing the combination immunotherapy studies with the greatest impact.
OncLive: What do we know about immunotherapy in stage IV disease?
: When looking at a patient with metastatic NSCLC, we first look at what type of histology they have–nonsquamous versus squamous–driver mutations they may have, specifically whether or not they have EGFR
or PD-L1 status. Immunotherapy may or may not be an option for most patients with driver mutations, specifically EGFR
. The first-line clinical trials did not include these patients. Right now, therapies such as tyrosine kinase inhibitors (TKIs) are recommended for first-line treatment of these patients.
For the majority of patients, the options are wide-ranging now. If you have PD-L1 staining of ≥50%, pembrolizumab as a single agent is still an option. We know this based on 2 studies. The KEYNOTE-024 study specifically looked at those with PD-L1 expression ≥50% and showed a survival advantage in those patients who received pembrolizumab. Also, the KEYNOTE-042 study looked at patients whose tumor proportion score (TPS) was 1% or greater and showed a survival advantage if they received pembrolizumab. My opinion is a lot of the benefit was mainly seen in patients with high PD-L1 expression, and that may have carried the survival benefit.
The bulk of the advances is in combining these kinds of agents with chemotherapy. The KEYNOTE studies of adding pembrolizumab to chemotherapy backbones showed an advantage to platinum-based doublets by itself in patients with metastatic disease.
Data from KEYNOTE-189 in nonsquamous cell histologies combining pembrolizumab with pemetrexed and carboplatin or cisplatin showed a survival advantage in patients compared with chemotherapy. KEYNOTE-407 combined carboplatin, paclitaxel, or nab-paclitaxel (Abraxane) with pembrolizumab versus a carboplatin-based doublet in squamous cell histology. It also showed a survival advantage when pembrolizumab was added to chemotherapy. Based on that, most of us would recommend the combination with chemotherapy.
Now, we have IMpower150 in which atezolizumab was combined with 3 other drugs: bevacizumab, paclitaxel, and carboplatin. That was compared with chemotherapy plus bevacizumab. While PFS was improved, OS was not improved. Most of us are quite interested in the fact that this is the only study that included EGFR
-mutated disease and showed an improvement in PFS in that group of patients when adding atezolizumab to chemotherapy and bevacizumab. It's quite intriguing, but we need to see larger studies with that subgroup of patients to feel comfortable combining that 4-drug regimen together in that patient population.