Executive Summary
Best of Lung Cancer Science at 2025 ASCO
The STS 2025 Best of Lung Cancer Science special edition podcast series offers members direct access to the most relevant and practice-changing science in lung cancer, curated and interpreted by thoracic surgeons for thoracic surgeons.
This executive summary breaks down the key takeaways on pivotal research and emerging themes from top studies presented at the 2025 American Society of Clinical Oncologists (ASCO) Annual Meeting.
Gain unique insights into new science that is redefining the surgical management and multidisciplinary care of lung cancer, as shared by Erin Gillaspie, MD, Chief of Thoracic Surgery, CHI Health, and podcast host, and Brendon Stiles, MD, chief, Division of Thoracic Surgery and Surgical Oncology, Montefiore-Einstein Comprehensive Cancer Center.
1. Neoadjuvant Immunotherapy and CheckMate 816: A Landmark in Lung Cancer Care
Dr. Stiles discussed the long-awaited 5-year survival results from the CheckMate 816 trial, the first phase III study testing neoadjuvant nivolumab plus chemotherapy versus chemotherapy alone in resectable stage IB-IIIA NSCLC.
• Overall survival: 65% for the nivolumab group vs. 55% for chemotherapy alone.
• Pathologic complete response (pCR): Strongly correlated with long-term benefit; patients achieving pCR had a 95% 5-year survival, with no lung cancer–related deaths in that subgroup.
• These findings confirm that delivering immunotherapy before surgery can induce durable cures in a subset of patients and that pCR is a reliable surrogate for survival outcomes.
Dr. Stiles emphasized that the field’s next major goal is to increase pCR rates through tailored neoadjuvant strategies and better predictive tools, including circulating tumor DNA (ctDNA) monitoring.
2. Escalation vs. De-escalation: Refining Perioperative Therapy
With perioperative immunotherapy trials such as CheckMate 77T, AEGEAN, and KEYNOTE-671, a major question has emerged: Do patients with complete pathologic response still need adjuvant therapy?
- While some oncologists favor continuing immunotherapy in higher-risk (e.g., stage III) patients, Dr. Stiles noted that it’s “hard to improve on 95% survival.”
- ctDNA clearance may soon guide escalation or de-escalation, identifying which patients can safely avoid additional therapy and which require intensified treatment.
- Importantly, patients with unfavorable mutations (STK11, KEAP1) still benefited from chemo-immunotherapy, underscoring that these regimens remain broadly advantageous.
Dr. Stiles and Dr. Gillaspie both noted that de-escalation strategies, whether reducing systemic therapy or limiting the extent of surgery, will be crucial for optimizing long-term quality of life and preserving future treatment options. Gillaspie likened this to “keeping cards in our back pocket” to use later if recurrence occurs.
3. Timing Matters: Circadian Influence on Immunotherapy Efficacy
A surprising ASCO highlight came from a Chinese randomized trial evaluating time-of-day effects on immunotherapy outcomes.
• Patients receiving chemo-immunotherapy before 3 PM had double the progression-free survival (13.2 vs. 6.5 months) compared to those treated later in the day.
• This validates earlier retrospective findings suggesting that circadian rhythm influences immune response, a field now termed circadian immunobiology.
• The results have generated widespread interest, prompting institutions to review their own treatment timing data.
4. The Neoadjuvant Osimertinib Era: NEOS (NeoADAURA) Trial
Following the success of ADAURA, which established adjuvant osimertinib as standard care for resected EGFR-mutant NSCLC, the NEOADAURA trial is testing whether neoadjuvant osimertinib, with or without chemotherapy, can further improve outcomes for patients with EGFR exon 19 deletion or L858R mutations.
This trial reflects a broader shift toward introducing targeted therapies earlier in the disease course and aligning surgical planning with biomarker-driven treatment decisions.
5. Expanding Surgical Boundaries and the Role of Biomarkers
In reflecting on the year’s trends, Dr. Stiles emphasized that the pendulum has clearly swung toward the neoadjuvant space, with surgery increasingly integrated into complex, multidisciplinary care for more advanced disease.
- Routine biomarker testing must become as standard as imaging, ensuring every patient is evaluated for actionable targets before therapy begins.
- New systemic agents are allowing surgeons to convert previously unresectable tumors into operable cases, expanding curative potential.
- Dr. Stiles also reaffirmed his belief that surgical local control remains superior to radiation therapy, especially when paired with optimal systemic treatment.
Main Points:
• Neoadjuvant therapy is now the dominant paradigm in resectable lung cancer, supported by long-term survival data.
• Comprehensive biomarker testing is essential for guiding both surgical and systemic strategies.
• De-escalation and escalation of both systemic and surgical treatments will increasingly be guided by ctDNA and response data.
• New drugs and novel combinations continue to expand treatment possibilities and challenge traditional staging boundaries.
• The integration of surgery and systemic therapy is creating opportunities to make “unresectable resectable.”
Bottomline:
Drs. Gillaspie and Stiles concluded that lung cancer care is entering an era defined by precision, flexibility, and collaboration. Surgeons will play a central role in multidisciplinary teams, leveraging biomarkers, liquid biopsy tools, and neoadjuvant innovations to personalize care, expand operability, and ultimately, improve cure rates.
As Dr. Stiles noted, “These are super exciting times. Our challenge now is to keep up with the science and stay in the space where we can offer patients their best systemic and local therapies.”