What’s Next for Lung Cancer Treatment?
Article Summary
- A nuanced understanding of tumor biology and the development of new therapies have resulted in better outcomes for many lung cancer patients.
- Sylvester researchers are calling for a concerted effort to ensure all lung cancer patients benefit fully from everything science and medicine have to offer.
- Targeted therapies and immunotherapies that boost the immune response to tumors have driven remarkable improvements in lung cancer patient survival.
Lung cancer is a serious, often fatal disease. But thanks to a more nuanced understanding of tumor biology and the development of new therapies, many patients fare significantly better than those diagnosed in past decades.
Within the next five to 10 years, faculty at the Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, foresee the field doubling down on some of the advancements, notably targeted therapies, that have driven this progress. Meanwhile, they call for a concerted effort to ensure all patients — regardless of their tumor type, race, ethnicity and other complicating factors — benefit fully from everything science and medicine have to offer.
Expanding Targeted Cancer Therapies
The U.S. Centers for Disease Control projects that in 2024, lung cancer will take the lives of 611,720 Americans, more than any other cancer. Even so, new treatments and therapeutic strategies are chipping away at its toll.
Earlier this year, a study in the Journal of Clinical Oncology described an exceptional example of this progress. It reported that 60% of non-small cell lung cancer patients who received lorlatinib, a drug that targets mutations in the ALK gene, had not seen their disease worsen five years after treatment. By comparison, a study in 2002 found that only 33% of patients with similar disease survived at least a year after receiving chemotherapy.
Lorlatinib is one of the medications the FDA has approved to kill cancer cells by exploiting specific abnormalities within them. These targeted therapies, along with immunotherapies that boost the immune response to tumors, have driven remarkable improvements in survival, according to Estelamari Rodriguez, M.D., M.P.H., co-lead of the Thoracic Site Disease Group at Sylvester and its associate director of outreach.
Oncologists now have reliable ways to fight many non-small cell tumors, which account for most lung cancers. However, options have remained much more limited for small-cell malignancies.
But that may be changing. In May, the FDA approved the first targeted therapy, tarlatamab, for small-cell tumors, which account for about 15% of lung tumors. This drug targets the DLL3 protein found on most small-cell tumors, while simultaneously directing the immune system to destroy these marked cells. Trials are now testing other small-cell-targeting compounds, some in combination with chemotherapy.
“That’s where the promise is for lung cancer, that we will keep making progress with molecular understanding and really tailoring drugs to people’s individual mutations,” Dr. Rodriguez said.
She also predicts that more incremental improvements, such as a better understanding of treatment resistance and avoidance of chemotherapy’s toxic effects, will benefit patients.
Better Screening for Earlier Lung Cancer Diagnosis
Sylvester’s oncologists say the field must focus on an opportunity it has so far missed: catching tumors early, when they are more treatable, perhaps even curable.
“Even though we’ve made great strides in lung cancer treatment, it is most often diagnosed at an advanced stage, so survival rates are poor,” said Coral Olazagasti, M.D., a Sylvester assistant professor of clinical medical oncology.
Identifying more early-stage tumors will require a few developments, including — but not limited to — changes in the screening guidelines. Currently, they call for screening smokers and former smokers between 50 and 80 years old who have a 20-pack-year or more history. (A pack year is equal to smoking one pack of cigarettes per day per year. The more heavily someone smokes, the faster they meet this criterion.) Those who qualify receive a scan known as low-dose computed tomography (LDCT).
Not only is the pack-year calculation prohibitively complicated, Dr. Olazagasti pointed out, but the guidelines miss many who may be at elevated risk. Oncologists report they are seeing more young patients with lung cancer, perhaps reflecting a wider increase in early-onset cancers. Meanwhile, research indicates that lung cancer diagnoses are rising among those who have never smoked. To better anticipate such cases, researchers need to understand the factors driving these trends.
What’s more, risk can vary with race and ethnicity. The guidelines, which were originally developed based on data collected nearly exclusively from white participants, do not account for these differences, Dr. Olazagasti said.
“It is not one size fits all,” she said. “What is considered a high-risk tobacco history for non-Hispanic whites may not be the same for non-Hispanic Blacks, or for Latinos or Hispanics.”
Given their inadequacies, Dr. Olazagasti expects to see the screening guidelines changed in the coming years. She hopes that the next iteration considers factors such as family history, race, ethnicity and education level to more comprehensively assess risk and tailor screening.
Better screening will also require new technology. Dr. Olazagasti said she anticipates a blood-based test, which could be used to determine who should receive LDCT, could become available within the next few years.
Better Lung Cancer Outcomes for All
Addressing disparities should be a major focus for the field over the near future, according to Dr. Rodriguez. Not only do oncologists need to ensure clinical trials enroll participants from diverse backgrounds, but they must also pay attention to the barriers that interfere with care, particularly for more vulnerable groups.
“The biggest take-home message is that advances in lung cancer research are bringing new treatments, but we still have a lot of work to do,” she said.
Tags: cancer research, cancer screening, Dr. Coral Olazagasti, Dr. Estelamari Rodriguez, immunotherapy, lung cancer, Sylverster Comprehensive Cancer Center, targeted chemotherapy, USNWR Oncology