Presentation by Jason Porter, MD, West Cancer Center
Many patients with lung cancer continue to be diagnosed at late stages of disease, when the cancer has spread outside of the lung (i.e., metastatic disease), but the use of advanced therapies, such as immuno-oncology (IO) agents, which stimulate the body’s immune system to attack cancer cells, has been transformative in the treatment of patients with many advanced cancers. At the 2022 OneOncology Conference held in Nashville, Tennessee, Dr Jason Porter from West Cancer Center discussed updates in the use of these agents in the setting of metastatic lung cancer.
There are currently three IO agents, also known as immune checkpoint inhibitors, that have been approved for use as first line (1L) single agent therapies (monotherapy) in metastatic lung cancer, pembrolizumab, atezolizumab, and cemiplimab. Other immune checkpoint inhibitors such as nivolumab and ipilimumab are used as a combination therapy (called the “Ipi-Nivo” regimen), and IO agents including pembrolizumab, cemiplimab, durvalumab, and tremelimumab have also been used in combination with established chemotherapy regimens (e.g., platinum doublet chemotherapy) that are commonly used in metastatic lung cancer. Notably, the use of IO agents is generally indicated for patients with NSCLC who do not have so-called ‘actionable’ or ‘driver’ molecular alterations in their tumors, such as mutations in the EGFR or ALK genes; such patients would be candidates for other NSCLC therapies which specifically target tumors with these genetic alterations.
Immunotherapy in mNSCLC: Long-Term Updates
For NSCLC patients who have positive expression of an immunotherapy target molecule, termed programmed death ligand-1, or PD-L1 in their tumors, Dr Porter noted that monotherapy with the approved IO agents in metastatic NSCLC results in overall survival (OS) rates of between 20 and 26 months (relative to ~13 months with chemotherapy) and overall response rates (ORRs) of between 38 and 46% (relative to 21 to 29% with chemotherapy). Although the data with pembrolizumab are considered to be the most mature at present, Dr Porter emphasized that similar efficacy data for the other IO monotherapies is expected with longer follow up data from major clinical trials. For patients on combined therapy with ipilimumab and nivolumab (Ipi-Nivo), Dr Porter noted results from the 5-year analysis of the CheckMate 227 Trial, which showed a benefit of the combination IO therapy in OS over chemotherapy in patients with both positive (>1% PD-L1; 24% vs. 14%) and negative (<1% PD-L1; 19% vs. 7%) PD-L1 expression. He suggested the Checkmate 227 regimen is an option if patients are unable to tolerate platinum doublet chemotherapy, regardless of their PD-L1 expression level.
Dr Porter noted that the efficacy of pembrolizumab in combination with chemotherapy as 1L treatment for metastatic NSCLC has also been confirmed across 2 major phase III clinical trials, KEYNOTE-189 (for non-squamous NSCLC) and KEYNOTE-407 (for squamous NSCLC). In these trials, the addition of pembrolizumab to either cisplatin/carboplatin and permetrexed (KEYNOTE-189) or carboplatin and paclitaxel/nab paclitaxel (KEYNOTE-407) significantly improved both OS and PFS, although Dr Porter emphasized the need for screening and diagnosing these cancers early, as survivorship continues to be poor for patients at advanced stages of disease. Notably, both of these studies showed an incremental effect of PD-L1 expression, such that patients with higher PD-L1 expression level in their tumors had better OS and PFS compared to those with lower expression of PD-L1.
Dr Porter also reviewed results from the EMPOWER Lung 3 Trial, which also confirmed the efficacy of the IO cemiplimab in combination with platinum doublet chemotherapy. In this trial, the median OS for patients on cemiplimab was 21.9 months versus 13.0 months for those on chemotherapy alone, and median PFS was 8.2 versus 5.0 months, respectively. There was an apparent incremental effect of PD-L1 expression in this study, such that those with higher PD-L1 expression had higher ORRs, ranging from 32.6% to 53.4% for those with the lowest and highest expression, respectively. Lastly, Dr Porter reviewed the 4-year results from the POSEIDON Trial recently presented at ESMO 2022. In this trial, patients were treated with a combination IO therapy (durvalumab with tremelimumab) and chemotherapy, or chemotherapy alone. OS was significantly improved at 48 months with the triple regimen as compared with chemotherapy alone (20.7% vs. 8.3%) and was also improved for patients who received durvalumab with chemotherapy (16.3% vs. 8.3%). The results favored combination therapy across all relevant subgroups of patients, and the findings from POSEIDON led to FDA approval for the durvalumab + tremelimumab regimen in combination with platinum-based chemotherapy as another option for patients with metastatic NSCLC.
A Call to Action: Lung Cancer Screening
Dr Porter began and ended his presentation with a call to action for lung cancer screening. As the second most commonly diagnosed cancer type in both men and women, lung cancer still accounts for more cancer deaths than the three most commonly diagnosed cancer types (colorectal, breast, prostate) combined. He also noted that the 5-year survival rate in NSCLC (~21%) is still relatively poor, as compared to the other commonly screened-for cancers, such as breast and prostate (~90 – 98%). He noted the value of lung cancer screening, using a simple and non-invasive low dose computed tomography (LDCT) methodology, and the results of major lung cancer screening trials, which show that appropriate screening can detect over 60% of patients with lung cancer at early stages (i.e., Stage IA and IB) which are much more curable relative to later stages. Despite these findings, which demonstrate that lung cancer can be detected in both smokers and non-smokers at earlier stages, Dr Porter emphasized that LDCT screening is still not currently available to everyone, and that “everyone with lungs can get lung cancer”. As such, Dr Porter believes there should be a continued push for expanded coverage and uptake of lung cancer screening for all individuals, regardless of their smoking history.
Immuno-oncology (IO) agents, which stimulate the body’s immune system to attack cancer cells, play a major role in the current treatment paradigm for patients with metastatic lung cancer, whether used as monotherapy, or in combination with chemotherapy.
Long-term updates from major phase III clinical trials of metastatic non-small-cell lung cancer continue to favor use of IO agents, alone or in combination with chemotherapy, over chemotherapy alone.
“Anyone with lungs can get lung cancer”, and if detected early, lung cancers are much more curable. Lung cancer screening using non-invasive low dose computed tomography (LDCT), however, is not currently available or covered by insurance for everyone.
See more from the 2022 OneOncology Conference here.
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