Shifting Paradigms in Lung Cancer Care: Insights From ASCO 2025
Transitions in lung cancer treatment drove the discussion at an Oncology Brothers Advancements in Oncology event held alongside the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Narjust Florez, MD, of Dana-Farber Cancer Institute, and Sandip Patel, MD, of UC San Diego Health, joined Rahul Gosain, MD, MBA, and Rohit Gosain, MD, to focus on precision medicine and patient-centered care. These leading oncologists emphasized the importance of individualized care, multidisciplinary decision-making, and the emerging role of circulating tumor DNA (ctDNA) in guiding therapy from stage I resectable tumors to advanced molecularly driven disease.
Early-Stage NSCLC: Nuance in Resectability and the Rise of Neoadjuvant Immunotherapy
Dr. Florez started the conversation by dissecting treatment options in stage I lung cancer, stressing that stages 1A and 1B should not be conflated. Tumor size, particularly a 4-cm threshold, guides whether adjuvant therapy is considered. Although surgery remains standard and uniquely provides valuable nodal staging, stereotactic body radiation therapy may be appropriate for medically inoperable patients.
Dr. Patel highlighted the underused power of low-dose CT screening to detect early-stage disease, especially in eligible patients. Advocating for novel diagnostics, such as blood-based assays, Dr. Florez called attention to nonsmoking populations who, like her own mother, fall outside current screening criteria. Dr. Florez is working on a study addressing this unmet need.
For stages II and III, the consensus leaned toward perioperative immunotherapy. The 3-cycle neoadjuvant chemotherapy plus nivolumab regimen from CheckMate 816 was praised for its simplicity and potential for pathologic complete response. For patients at higher risk or with positive nodes, however, studies like KEYNOTE-671, AEGEAN, and CheckMate 77T suggest a benefit from adjuvant immunotherapy. Social determinants (eg, distance to care centers) and patient preference emerged as essential when deciding between short-course and extended immunotherapy regimens.
Next-Generation Sequencing Before PD-L1: A Caution Against Premature Immunotherapy
The panel unanimously emphasized that PD-L1 results alone should not guide upfront treatment decisions. Dr. Patel noted that PD-L1 expression can be misleading: Although 40% to 60% of EGFR/ALK-positive tumors also show high PD-L1, these patients derive minimal benefit from immunotherapy and are better served with targeted agents.
Metastatic EGFR-Positive Disease: A Debate of Strategy and Tolerability
As new data emerge on osimertinib combinations and amivantamab-lazertinib (ami-laz), the optimal frontline regimen for EGFR-mutant non–small cell lung cancer (NSCLC) remains uncertain. Dr. Florez highlighted the importance of interpreting promising progression-free survival curves in the absence of overall survival data (eg, FLAURA2). She also pointed out that skin toxicity from dual-targeted therapy with ami-laz is an important consideration, especially with young patients seeking normalcy in their personal lives.
The discussion of sequencing also revealed strategic trade-offs: Using pemetrexed-based chemotherapy up front may limit future access to novel agents like patritumab deruxtecan (HER3-DXd) or MET-targeted therapies. Tissue-based rebiopsy at progression was deemed essential, particularly to identify small cell transformation or MET/HER2 overexpression not detectable via liquid biopsy.
ALK-Positive Disease and the “Ferrari” of Tyrosine Kinase Inhibitors
When polled on their preferred first-line ALK tyrosine kinase inhibitor (TKI), both Dr. Patel and Dr. Florez leaned toward lorlatinib, especially for patients with brain metastases. Although lorlatinib is more potent, its toxicity profile demands careful management. Dr. Florez described it “like learning to drive a Ferrari.” However, for patients seeking long-term disease control, the survival advantage justifies the learning curve.
Dual Immunotherapy and Uncommon Mutations
In PD-L1-negative, STK11, or KEAP1-mutant tumors, dual checkpoint blockade (eg, nivolumab-ipilimumab) is considered, particularly in young patients or those with squamous histology or brain metastases. While benefits are modest, responders can achieve long-term survival. Dr. Patel highlighted data showing that mild immune-related adverse events may correlate with better outcomes.
Small Cell Lung Cancer: Renaissance Era
In limited-stage small cell lung cancer (SCLC), the ADRIATIC trial introduced durvalumab as the post-chemoradiotherapy standard for 2 years, doubling the duration seen in PACIFIC for NSCLC. Prophylactic cranial irradiation remains debated. Because of concerns about long-term neurotoxicity, Dana-Farber Cancer Institute has trended toward MRI surveillance.
In extensive-stage SCLC, the IMforte study (if approved) may bring a new chemo-IO backbone. Dr. Patel framed it as repurposing already available ingredients to achieve incremental gains in survival. With agents like tarlatamab on the horizon, SCLC may finally be entering its own era of precision therapy.
Tarlatamab and Equity in Innovation
Although tarlatamab holds promise, Dr. Florez cautioned that its complexity and resource demands could widen disparities, especially for rural and community oncologists. She urged academic centers and developers to ensure training and infrastructure support to avoid “dropping fancy drugs into unprepared clinics.”
A Patient-Centered Future: Circulating Tumor DNA and Adaptive Therapy
The final moments of the panel centered on a moving question from patient advocate Jill Feldman: Could ctDNA eventually enable adaptive therapy and treatment holidays? Dr. Florez affirmed the idea, citing examples of patients pausing therapy to pursue fertility or other life goals. While ctDNA isn’t ready for prime time, it may soon help determine when patients can consolidate, stop, or switch therapies.
Conclusion:
The panel highlighted a dynamic shift toward precision medicine and patient-centered care. As new agents reshape the therapeutic landscape, oncologists must balance molecular complexity, treatment tolerability, and patients’ lived experiences to deliver optimal outcomes.