Expert Explains Approaches in Non-Driver NSCLC

Gina Columbus @ginacolumbusonc
Published Online: Thursday, Aug 17, 2017

Lyudmila A. Bazhenova, MD
Lyudmila A. Bazhenova, MD
The angiogenesis inhibitor bevacizumab (Avastin) has remained a go-to standard for patients with non-driver, nonsquamous non–small cell lung cancer (NSCLC), which comprises nearly one-quarter of the overall lung cancer population. PD-1/PD-L1 inhibitors have also demonstrated promising outcomes as monotherapy and in combination with chemotherapy.

An ongoing clinical trial is combining bevacizumab with immunotherapy, hoping to propel patients into deeper responses. The randomized, open-label phase III IMpower150 study is evaluating the safety and efficacy of atezolizumab (Tecentriq) in combination with carboplatin/paclitaxel with or without bevacizumab versus treatment with carboplatin/paclitaxel plus bevacizumab in chemotherapy-naïve patients with stage IV nonsquamous NSCLC (NCT02366143).

In an interview with OncLive, Lyudmila A. Bazhenova, MD, medical oncologist, professor of medicine, UC San Diego Health, discussed the non-driver NSCLC population, the treatment strategies available for them, and challenges physicians continue to face with this subgroup of patients.

OncLive: What is the prevalence of patients with non-biomarker driven nonsquamous lung cancer?

Bazhenova: The data behind prevalence of different targeted mutations in lung cancer comes from The Cancer Genome Atlas (TCGA). In this data, we see that approximately one-quarter of patients, about 25%, do not have any genetic mutations. In the TCGA database, we also see that maybe about 30% of patients with lung cancer have a KRAS mutation. It is a very prevalent mutation but, at this point, we really cannot target that mutation.

If you look at the incidence of EGFR mutations in all patients with nonsquamous NSCLC, it is approximately 10% to 15%, and ALK mutations are in about 5%. Then, you have much rarer mutations, like ROS1, which is in about 1% to 2%. Then, you go even smaller populations like BRAF, HER2, and others. 

Please discuss the variation in treatment approach between patients with driver mutations versus those without.

When one decides what is the best thing to do for their patients with newly diagnosed nonsquamous NSCLC, certain tests need to be done. You have to know what the patient's EGFR, ALK, and ROS1 mutation status is, and what is the patient’s expression of PD-L1. If you have a patient with PD-L1 expression of more than 50%, the treatment of choice would be pembrolizumab (Keytruda), based on the randomized study comparing pembrolizumab versus chemotherapy that showed improvement in patients who were randomized to pembrolizumab.

For patients with ROS1-mutant lung cancer, I would be prescribing them crizotinib (Xalkori). For patients with EGFR-mutant lung cancer, you currently have 3 drugs that are FDA approved, which are erlotinib (Tarceva), gefitinib (Iressa), and afatinib (Gilotrif). We are eagerly awaiting the release of the FLAURA study,* which will be released at the 2017 ESMO Annual Congress. This is a study that compared osimertinib (Tagrisso) versus [standard-of-care EGFR tyrosine kinase inhibitors, either erlotinib or gefitinib] to look for an improvement in outcomes of those patients. 

Let’s discuss bevacizumab. What impact have you seen the angiogenesis inhibitor have on the non-driver NSCLC population?

Bevacizumab has been approved in lung cancer based on the ECOG E4599 study. In this study, patients were randomized to carboplatin/paclitaxel versus carboplatin/paclitaxel plus bevacizumab. The study showed an improvement in outcomes. There were improvements in response rate, progression-free survival (PFS), and overall survival.

However, one has to remember that bevacizumab has contraindications. Number one, bevacizumab is contraindicated for patients with squamous cell carcinoma, contraindicated for patients with uncontrolled hypertension, and for patients with significant bleeding and clotting history. 

What is the utility of immunotherapy in this population?

[It is generally] for patients with newly diagnosed lung cancer, that is metastatic stage IV, who have a high expression of PD-L1 on the tumor that is defined, at this point, as more than 50% of the tumor cells expressing PD-L1. Pembrolizumab improves outcomes.


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Oncology Best Practice™: Informed Decision Making in Advanced NSCLC: Matching Treatment to PatientOct 25, 20171.0
Community Practice Connections™: 17th Annual International Lung Cancer Congress®Oct 31, 20171.5
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