Improving Therapy Options and Patient Experiences in NSCLC: Part 1

Key Takeaways:

• Enhancements in disease management: Evolutions in biomarker testing and expanded treatment options for NSCLC have led to improved treatment decision-making among physicians and patients.
• Prolonged survival: Targeted therapies are associated with better survival outcomes, resulting in the rise of long-term survivors among patients with NSCLC.
• Ongoing NSCLC research: The LUNGevity Foundation is supporting patient-focused studies addressing current gaps in treatment and implementation.

In this interview, Upal Basu Roy, PhD, MPH, executive director of research at LUNGevity, discusses how developments in therapies for non–small cell lung cancer (NSCLC) have improved the overall treatment landscape. He shares the ways LUNGevity is contributing to ongoing research aimed at closing gaps in care and improving the patient experience.

Upal Basu Roy, PhD, MPH: I am Dr Upal Basu Roy, the executive director of research at the LUNGevity Foundation. I manage the foundation’s research program and have worked in lung cancer advocacy since 2015.

How has the treatment landscape for NSCLC evolved over the past decade, and which advances have had the greatest impact on clinical pathways and treatment selection?

Dr Basu Roy: The past decade has turned NSCLC from essentially 1 disease treated with platinum chemotherapy into a collection of molecularly defined diseases, each with its own treatment path. In my opinion, 5 noticeable shifts have transformed how lung cancer is managed today.

The first is the expansion of actionable biomarkers. Ten years ago, EGFR and ALK were the main targets. Today, pathways must account for EGFR (including exon 20 insertions), ALK, ROS1, BRAF V600E, KRAS G12C, MET exon 14 skipping, RET, NRG1, NTRK, and HER2, among others. That expansion is what made comprehensive, next-generation sequencing (NGS)–based testing the standard rather than sequential single-gene tests, and it has made the biomarker result the most important branch point in the pathway.

The second big shift has been the introduction of immunotherapy. Checkpoint inhibitors, alone or combined with chemotherapy, became the backbone of first-line therapy for patients whose tumors do not have a targetable driver mutation, with the programmed death-ligand 1 (PD-L1) protein expression guiding selection. Immunotherapy has also forced us to rethink how health care should be delivered. Now, it is important to know the driver mutation status before starting immunotherapy, because giving immunotherapy to a patient with, for example, EGFR-mutated NSCLC can mean less benefit and added toxicity risk when switching to a targeted therapy.

The third, and possibly most important for pathways right now, is the movement of targeted therapy and immunotherapy into early-stage disease. Adjuvant osimertinib for resected EGFR-mutant disease, adjuvant alectinib for resected ALK-positive disease, and adjuvant selpercatinib for resected RET-positive disease, along with neoadjuvant and perioperative chemo-immunotherapy, have all changed the standard of care. The practical consequence is that biomarker testing, including PD-L1, EGFR, ALK, and RET, now needs to happen at diagnosis for early-stage patients. This has necessitated multidisciplinary coordination between surgery, radiation, pathology, and medical oncology from the start.

Fourth is the increasing sophistication of first-line treatment options and treatment sequencing, including intensified first-line strategies in EGFR-mutant disease, bispecific antibodies, and antibody-drug conjugates, as well as the use of liquid biopsy to speed testing and track resistance. This expansion has also added complexity, which is why well-designed pathways matter more than ever.

Lastly, people are now living longer with lung cancer than ever before. Recent data from the phase 3 CROWN trial shows that 55% of patients receiving lorlatinib for ALK-positive lung cancer didn’t have any disease progression after 7 years. Similarly, in the Keynote-010 trial, 11.3% of patients who received immunotherapy were alive after 10 years. This new emerging population of long-term survivors has unique needs, and clinical pathways should incorporate survivorship discussions on how best to serve this emerging community.

Can you explain some of the ongoing research you are overseeing at LUNGevity and how it fits into the broader NSCLC landscape?

Dr Basu Roy: We have taken 2 deliberate and complementary approaches toward supporting research.

The first is funding translational research. Our 2026 grant cycle reflects where we see the greatest unmet need. In partnership with Rising Tide for Clinical Cancer Research, we opened the cycle with 5 research programs, including the RTFCCR-LUNGevity Resistance and Recurrence Award, $1 million over 4 years to address treatment resistance and early detection of recurrence. That focus is deliberate. Targeted therapies and immunotherapy have extended survival dramatically, but nearly all targeted therapy eventually stops working, so understanding and anticipating resistance is now a central question in NSCLC. Funded projects are expected to have a direct impact on early detection and outcomes, or to provide a foundation for future methods of early detection and individualized treatment, including targeted therapy and immunotherapy.

We also invest heavily in the workforce. Programs like our Career Development Award, the Health Equity and Inclusiveness Research Fellow Award, the VA Research Scholar Award, and the ASTRO-LUNGevity seed grant for radiation oncology trainees are about making sure the field has researchers ready to carry this work forward. Since 2002, LUNGevity has invested more than $59 million into translational research.

The second level is implementation and patient-focused research, which is where we fill a gap that few other organizations address. Through our Patient-Focused Research Center founded in 2016, we have been studying how people at high risk of developing lung cancer access lung cancer screening and how people are living with lung cancer. Our studies have enabled us to understand implementation gaps in screening, access to precision medicine, and access to clinical trials.

Through our work, we connect patient voice with health care professionals, regulators, policymakers, and drug developers, generating evidence directly from patients and caregivers about how they access care and experience a lung cancer diagnosis. In addition to the studies conducted through our Patient-Focused Research Center, our Precision Medicine team has done a lot of work on getting biomarker testing into the diagnostic workflow, including tissue acquisition.

Taken together, this work reflects a simple reality in NSCLC today: science is outpacing how health care is delivered. A new targeted therapy only helps a patient whose tumor was tested, whose results came back in time, and whose care team had a therapy option for them. Our portfolio is designed to address both halves of that equation.