Precision Oncology and the New Era of Lung Cancer

The landscape of thoracic oncology has undergone a seismic shift over the last 2 decades. Where once a diagnosis of advanced lung cancer offered few paths forward, the advent of precision medicine has transformed the field into one of the most dynamic areas of modern medicine. Bruna Pellini, MD, chief of Thoracic Medical Oncology at Baptist Health Miami Cancer Institute, specializes in treating uncommon mutations and discussed how to navigate the increasingly complex web of targeted therapies.

“Being a thoracic oncologist in 2026 is far more complex than even in the early 2000s,” Pellini noted in an interview with Targeted Oncology. “It used to be that most people didn’t want to treat lung cancer 20 years ago because we didn’t have many options. And now we have new drug approvals every year.”

Understanding the "Glitches": Fusions vs Mutations

For many patients, especially those who have never smoked, the drivers of their cancer aren’t always traditional mutations. Pellini emphasized the importance of understanding fusions, a distinct genomic event.

“Most of [the uncommon mutations oncologists see] are actually not mutations. They are fusions, which is basically when a gene breaks apart and glues to another one and then starts activating the cancer cells,” she explained.

This distinction is vital for the patient population in South Florida, where Pellini works. She highlighted that a large, young patient population, particularly female and Hispanic patients, shows a higher incidence of these specific genomic alterations. “Hispanic patients have higher incidence of certain genomic alterations in their cancers. So that makes this topic extremely important for our patient population,” she said.

Breaking the Stigma and Expanding Screening

One of the most significant hurdles in lung cancer care remains the social stigma surrounding the disease. Pellini is a vocal advocate for expanding screening beyond the current, often narrow, guidelines.

“We have to stop the stigma,” she says. “The guidelines that we have nowadays, they do not encompass all potential patients that can have lung cancer, which leads a good proportion of them without any ways of detecting this disease in its early stages.” Her message is clear and inclusive: “If you have lungs, you can have lung cancer.”

A Banner Year for Targeted Therapies

The rapid-fire pace of drug approvals is a point of immense optimism for Pellini. In the past year alone, the arsenal for treating rare alterations like HER2, ROS1, and ALK has expanded significantly.

For many years, lung cancer specialists looked at the success of their colleagues in breast cancer with envy regarding HER2-targeted treatments.

“I remember when I started my career... we would always see our breast colleagues with all these therapies that were so effective for breast cancer patients, and we didn’t see the same success for lung cancer. And now we have 3 [HER2-targeted] drugs [for lung cancer],” she said, noting the FDA approvals of trastuzumab deruxtecan (T-DXd; Enhertu),¹ zongertinib (Hernexeos),² and sunvozertinib (Zegfrovy).³

Beyond HER2, the treatment of ROS1-positive non–small cell lung cancer (NSCLC) has seen a breakthrough with taletrectinib (Ibtrozi), approved in June 2025.⁴

“The newer generation of ROS1 inhibitors had a lot of toxicity when it comes to the central nervous system, causing dizziness,” she noted. “This drug does not have that [adverse] effect... being dizzy all the time and having a fear of falling is detrimental to your quality of life.”

The "CROWN” Jewel of ALK Inhibitors

When discussing ALK-positive NSCLC, Pellini points to the CROWN trial (NCT03052608) results for lorlatinib (Lorbrena) as a watershed moment in oncology. Five-year follow-up data were presented at the 2024 ASCO Annual Meeting and showed the longest progression-free survival ever reported in NSCLC.⁵

“I remember being at ASCO and us seeing the Kaplan-Meier curve... showing patients that got this drug, as opposed to the older generation drug, them being so far apart and at 5 years, the median progression-free survival not even being reached. We’re talking about stage IV [NSCLC]. We had never seen these curves before.”

Advice for the Community: "Don't Be Shy"

For oncologists in the community who may not encounter these rare "glitches" daily, Pellini offers straightforward advice: lean on the guidelines and your peers.

“First of all, [oncologists] should look at ASCO guidelines and the NCCN guidelines. We do live guidelines updates, so even when there’s newer approvals, we try to make the newer data available in a summarized fashion,” she said. Furthermore, she encourages a culture of collaboration. “Don’t be shy. Reach out to a colleague that is a specialist... we should always help each other.”

The Horizon: Liquid Biopsies

Looking toward the future, Pellini’s passion lies in liquid biopsies. She envisions a world where blood tests replace or supplement traditional imaging for monitoring disease.

“I believe using blood-based tests to monitor disease response to detect early signs of disease recurrence before radiographic imaging is able to is the future,” she said.

While she acknowledges that there is currently limited clinical utility for liquid biopsies in early-stage NSCLC, she is confident that the ongoing research will soon change the standard of care. “Lung cancer now is a chronic disease, and I’m very happy that that’s the case.”

REFERENCES

1. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer. News release. US FDA. August 16, 2022. Accessed February 6, 2026. https://tinyurl.com/yp2m9j9y

2. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. News release. US FDA. August 8, 2025. Accessed February 6, 2026. https://tinyurl.com/fbakh64s

3. FDA grants accelerated approval to sunvozertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. US FDA. July 2, 2025. Accessed February 6, 2026. https://tinyurl.com/52k2z4z6

4. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. News release. US FDA. June 11, 2025. Accessed February 6, 2026. https://tinyurl.com/4p8pky8w

5. Solomon BJ, Liu G, Felip E, et al. Lorlatinib vs crizotinib in treatment-naïve patients with advanced ALK+ non-small cell lung cancer: 5-year progression-free survival and safety from the CROWN study. J Clin Oncol. 2024;42(suppl 17):LBA8503.