Targeted Therapy Developments and Screening Updates Broaden the NSCLC Treatment Paradigm

Alexis Chidi, MD, PhD, MSPH

A push for advances in precision medicine has introduced more approaches to target mutations in non–small cell lung cancer (NSCLC), such as those in ALK, ROS1, and EGFR, according to Alexis Chidi, MD, PhD, MSPH, who added that the increasingly wide range of treatment options can help guide treatment selection for patients with early-stage to advanced-stage disease.

“One of the things I tell patients is that there’s never been a better time [to receive NSCLC treatment than now because of advances we’ve seen],” Chidi said during an interview with OncLive® following a State of the Science Summit™ on lung cancer, which she co-chaired. “Our ability to specifically target each of these mutations and to have not only first-line, but also second- and third-line options, is incredible.”

In the interview, Chidi emphasized the developments made in the NSCLC treatment paradigm regarding precision medicine directed against targetable mutations, the expansion of EGFR-targeted therapies in nonmetastatic settings, and current updates to lung cancer screening eligibility criteria.

In another article, Chidi highlighted the positive effects that surgical advances have had on the treatment of patients with NSCLC.

Chidi is an assistant attending surgeon and co-director of the Lung Cancer Screening Program at Memorial Sloan Kettering Cancer Center in New York, New York.

OncLive: How have targetable mutations helped refine NSCLC treatment approaches?

Chidi: Targetable mutations and PD-L1 have dramatically changed the paradigm for patients. For patients with nodal disease or large tumors, we are increasingly using targeted therapies or neoadjuvant immunotherapy, [which have induced] incredible responses. There are significant rates of pathologic complete response during the time of surgery for patients who have early-stage tumors, and we’re using each of these [targeted] agents more in the perioperative setting, as well. For patients who are not surgical candidates, we also have an increasing [number of] options for [managing] advanced-stage disease with [targeted therapy] combined with radiation therapy, and in the metastatic setting, we’re seeing significant improvements in long-term survival using novel [targeted] agents.

How is the use of EGFR-directed therapy expanding?

We are currently expanding our use of EGFR-targeted therapy into more areas. Initially, EGFR-targeted therapies were used in the metastatic setting. Currently, there has been some debate about whether these targeted agents should be used with chemotherapy, and about whether they’re better used alone or in combination with other therapies. We have additional information about which mutations are more susceptible to which agents. We have an expansion of the agents that are currently available. The [most important factor] is considering the different indications [for these agents]. That’s one of the [aspects of treatment] that’s changed the most over time—it’s an exciting area of inquiry.

How have the lung cancer screening eligibility criteria evolved over time? What might the future look like in this area?

Right now, depending on the source, we’ve demonstrated that between approximately 5% and 15% to 20% of people who are eligible for [lung cancer] screening are receiving it, so the biggest [screening-related] challenge right now is making sure people know about lung cancer screening. The current eligibility criteria, based on the United States Preventive Services Task Force, are anyone who’s 50 to 80 years old and has smoked an average of 1 pack [of cigarettes] a day for 20 years. [Those screening guidelines] only recommend screening for people who have smoked within the past 15 years.

However, there are additional guidelines from the American Cancer Society that don’t include that recommendation based on quitting, and [those guidelines are] based on how much a patient has smoked in the past. The National Comprehensive Cancer Network guidelines are based on the amount of time that a patient has smoked. If someone smoked for 20 years or more, no matter how much they’ve smoked, they are still eligible for screening. There are a lot of opportunities to keep working to ensure people are learning about screening, getting the screenings they need the first time, and making sure that if they’ve undergone one screen, they come back for their subsequent screenings.

We know that lung cancer screening is effective, and our goal is to try to bring that to more people. [Approximately] 90% of the time, the cancers we find with screening are early-stage cancers, so [we have] an opportunity to change the landscape of lung cancer right now. Usually, 20% to 30% of the cancers that we diagnose are only early stage. Shifting that from 20% to 30% to 90% would be a dramatic difference. We have a huge public health opportunity, and everybody who’s involved in lung cancer care is hopeful that we can continue working on this.