Recent Advancements in the Non–Small Cell Lung Cancer Treatment Landscape

In this interview, Sandip Patel, MD, University of California, San Diego, provides an overview of the latest treatment options for non–small cell lung cancer (NSCLC) and the importance of biomarker testing in this area.

Please introduce yourself by stating your name, title, organization, and relevant professional experience.

I'm Sandip Patel, MD, a medical oncologist and professor of medicine at the University of California, San Diego. I've been working in medical oncology—specifically thoracic oncology—and phase 1 trials for a little over a decade now.

Can you discuss some of the recent advancements in NSCLC treatment?

We've had numerous advances in the treatment of NSCLC, driven by our ability to subidentify patient populations that'll benefit from the treatment. NSCLC is probably a couple dozen diseases, but at least there are currently a dozen different diseases that we can treat with various agents, including targeted therapy, chemotherapy, and various targets that are on the horizon.

Some of the most recent advances include the use of epidermal growth factor receptor (EGFR) targeting in the metastatic setting in the post resection setting after surgery. In addition, most recently, after the post-concurrent chemoradiotherapy setting with drugs such as osimertinib, or in the advanced setting with drugs like osimertinib with chemotherapy, amivantamab with osimertinib, and various others.

Some of the areas that are particularly exciting are targeting novel oncogenic proteins in different ways, such as KRAS, KRAS G12C, and other KRAS variants, as well as the development of novel immunotherapeutic approaches for which programmed cell death protein 1 (PD1)-directed and cytotoxic T-lymphocyte associated protein 4 (CTLA-4)-directed approaches remain the current standard of care. Many of the advancements that we have in NSCLC are dependent upon us identifying the molecular subset that a patient may be a part of that can give them an opportunity for targeted therapy. And if not, there may be an opportunity for immunotherapy for many of these patients.

Are there any promising emerging therapies or ongoing clinical trials in the field of NSCLC that you believe may have a significant impact on future treatment approaches?

There are many clinical trials that are ongoing to address NSCLC, which is the leading cause of cancer-related mortality in the US and worldwide. Many of these are focused on new therapies for different targets, including pan-KRAS inhibition, for example, outside of the existing two Food and Drug Administration (FDA)-approved KRAS G12C mutation targeting agents, adagrasib  and sotorasib. Targeting other KRAS alleles and better understanding how we can use immunotherapy to target various subsets with PD-1 and CTLA-4 inhibition are the hottest areas in NSCLC.

Additionally, with the advent of potent antibody drug conjugates (ADCs) that can deliver highly potent chemotherapy optimally and directly to the cancer cell, there are a variety of targets in ADCs that are currently under investigation in clinical trials. Another, more thematic area of which there's a lot of active clinical trial interest is in the neoadjuvant and perioperative setting where patients receive therapy either entirely before or before and after their surgical procedure. The goal is to improve curative intent outcomes in a larger number of patients with immunotherapy but also increasingly targeted therapy.

What are some ways that patients can get access to clinical trials and how can clinical pathways help?

The best way for a patient to better understand all their treatment options, including clinical trials, is to ask their doctor about what their clinical trial options may be. And in asking the caregivers and providers using clinicaltrials.gov, there are also a variety of other resources for patients, including patient advocacy groups. In addition, molecular testing reports often have clinical trials listed in the packet that patients will receive along with their molecular testing results.

One way clinical pathways can help patients find the right clinical trial is to build trials into clinical pathways when available at a given site. This will nudge the physicians to think about these clinical trials and to make advanced knowledge generalizable for all patients, but also to help a specific patient in a rational design clinical trial, which may be testing a novel combination, which may become the standard of care eventually. Thinking about clinical trials as part of the pathway as opposed to being something that's separate is important in offering patients all their treatment options, including standard of care but also the opportunity to participate in a clinical trial if they so choose.

Is there anything else you'd like to add? Any final thoughts?

We’ve had a number of treatment option available for patients with NSCLC, but it's really driven by our ability to get appropriate biomarker testing. And so, for patients with metastatic NSCLC, a next-generation sequencing panel either in tissue or as a liquid biopsy is key to understand not only their right therapeutic path in terms of targeted therapy, but also making sure we don't inadvertently give immunotherapy to a patient who may better benefit from a targeted therapy approach. Getting the appropriate molecular testing is key in the localized setting.

EGFR is a must now along with anaplastic lymphoma kinase (ALK) in many settings. Getting the right test for the right patient in NSCLC is just as important as understanding estrogen receptor/progesterone receptor (ER/PR) and HER2 status in breast cancer. Increasingly, our ability to discern this information is important with NSCLC. One advantage we may have, at least in metastatic disease, is this can be done as a liquid biopsy if tissue is not available.