How Recent Lung Cancer FDA Approvals are Shaping Treatment for Patients

Dr. Brian S. Henick, a medical oncologist at Columbia University Irving Medical Center and director of the phase 1 program and translational research in aerodigestive cancers, outlined in an interview with CURE how recent FDA approvals are shaping treatment for patients with lung cancer.

He emphasized that lung cancer is a group of distinct diseases. Treatment decisions begin with histology, such as adenocarcinoma versus squamous cell carcinoma, followed by molecular testing. In lung adenocarcinoma, newer approvals are targeting mutations like MET overexpression and EGFR. These include antibody-drug conjugates, monoclonal antibodies and combination approaches with tyrosine kinase inhibitors and chemotherapy, which are improving outcomes compared with earlier options.

In contrast, fewer recent advances have emerged for lung squamous cell carcinoma beyond immunotherapy. Some newer combinations are being studied, though not all have shown clear benefit.

Henick also highlighted challenges in managing immune-related side effects from checkpoint inhibitors. As these therapies are used earlier in treatment, side effects may occur sooner and require long-term monitoring. While oncologists are more familiar with these toxicities, it remains difficult to determine when to start steroids or refer patients to specialists. Efforts are ongoing to identify strategies that reduce steroid use while maintaining treatment benefit.

CURE: For patients with lung cancer or other aerodigestive cancers, which recent FDA approvals have most significantly changed first-line treatment, and who is most likely to benefit from them?

Henick: This is a great question. To start, it helps to explain how we think about lung cancer. We tend to think of lung cancer as a group of different cancers rather than a single disease. What I mean by that is lung cancers share certain features, such as a tumor growing in the lung. When you look under the microscope, the cancer may also appear similar across many patients. However, there are still important differences. One of the first things we evaluate is the histology, or the specific subtype, of lung cancer.

That distinction is important because we treat lung adenocarcinoma very differently from lung squamous cell carcinoma.

For lung adenocarcinoma, the next key piece of information is which mutations are present in the cancer. Some of these mutations can be targeted with treatments that have been available for years, while others now have therapies that were approved more recently.

For example, in patients with lung cancer that over-expresses a protein called MET, a new antibody-drug conjugate has been approved for that specific indication. This has made an impact for that subset of patients. MET has long been a target of interest in lung cancer. Certain MET-skipping mutations have been treatable with different drugs for several years, but targeting MET over-expression has only recently become possible with this newer therapy.

Across many of the mutations we see in lung cancer, there have been new approvals in the last few years. For example, in EGFR-mutated lung cancer, monoclonal antibodies and bispecific antibodies have recently been approved for use in combination with tyrosine kinase inhibitors. Tyrosine kinase inhibitors are also now being combined with chemotherapy. These strategies are producing better outcomes than what we previously saw when patients were treated with tyrosine kinase inhibitor pills alone.

For lung squamous cell carcinoma, however, there has been less recent progress compared with adenocarcinoma. Much of the major progress came with the introduction of immunotherapy several years ago. This remains an area where we hope to see more advances soon.

There was recently a randomized study evaluating checkpoint inhibitors combined with antibodies that block factors that help tumors grow blood vessels. This combination was studied as an alternative to chemotherapy after first-line treatment. Unfortunately, the study did not meet its primary endpoint and did not show a clear benefit over existing treatments. However, it did demonstrate a better safety profile, so it may still represent a potential future option.

Overall, there are many reasons to be hopeful. The most effective treatment strategy depends heavily on the specific subtype of lung cancer and the molecular features of the tumor.

With more immunotherapy options now approved, how are doctors managing immune-related side effects differently than in the past, especially for patients who want to avoid long-term steroid use?

This is a major challenge. Increasingly, checkpoint inhibitors are being used not only in advanced metastatic cancer but also in earlier-stage disease, including before surgery. Because of this, the side effects associated with these treatments may appear earlier in a patient’s treatment journey. It also means oncologists need to remain alert for these complications for a long time after a patient has received the therapy.

The risk of side effects is typically higher earlier in the treatment course. The advantage, however, is that these drugs have been used for several years now. Most oncologists are familiar with the range of immune-related side effects that patients can experience.

Even so, it can still be difficult to determine when a patient should begin steroid treatment or when they should be referred to a specialist. At our academic institution, the threshold for referring a patient to a subspecialist is very low. We work closely with physicians who focus specifically on managing these immune-related side effects. Engaging them early allows us to consider alternative medications that may help manage symptoms while potentially reducing the need for long-term steroid use.

Unfortunately, we still do not have a reliable test that can predict which patients will develop severe immune-related side effects or require prolonged steroid treatment. At the moment, we often have to respond to these issues after a patient has already been exposed to the therapy.

We do know that certain groups of patients may face higher risks. For example, patients with a history of autoimmune disease or those who have undergone organ transplantation may be more vulnerable to these side effects. These individuals were often excluded from the original clinical trials that studied checkpoint inhibitors.

Looking ahead, continued use of these treatments will likely increase awareness of these side effects among both doctors and patients. Maintaining a low threshold for specialist referral and expanding research efforts will be important steps in improving management strategies.

One area that may also help advance the field is stronger patient advocacy around immune-related side effects from checkpoint inhibitors. At the moment, broad advocacy efforts focused specifically on these toxicities are limited. Increasing patient engagement in this area could help connect patients with researchers studying these complications and support the development of better treatment strategies.

Transcript has been edited for clarity and conciseness.

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