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The Best Science Presented at the 2026 American Society of Clinical Oncology Annual Meeting  

The STS 2026 Best of Lung Cancer Science special edition podcast series provides members with direct access to the most clinically relevant and practice-informing advances in lung cancer, curated and interpreted by thoracic surgeons for thoracic surgeons.

This executive summary focuses on key takeaways from the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, where groundbreaking targeted therapies, artificial intelligence (AI) in pathology, and adaptive, response-driven trial models dominated the lung cancer track.

Join host Erin Gillaspie, MD, MPH, Associate Professor with Tenure, CHI Health, and Jonathan Villena-Vargas, MD, Assistant Professor of Cardiothoracic Surgery at New York Presbyterian/Weill Cornell Medical Center, as they analyze immediate practice-changing discoveries, the expanding boundaries of resectability, and the imperative for multidisciplinary thoracic oncology. 

1. Adjuvant Targeted Therapy in RET Fusion-Positive NSCLC

  • The ASCO 2026 plenary session featured the first major readout from the LIBRETTO-432 trial.
  • Evaluating the efficacy of selpercatinib, a highly selective, brain-penetrant, potent RET inhibitor as adjuvant therapy in early to locally advanced RET fusion-positive NSCLC.
  • The trial demonstrated a strong event-free survival benefit, reflecting a substantial reduction in recurrence and death events in the selpercatinib arm compared with observation.
  • While acknowledging that this further contributes and supports the use of targeted agents in the adjuvant space, investigators emphasized ongoing careful consideration of toxicity and long-term tolerability.
  • Treatment-limiting adverse events, particularly hepatotoxicity, raised concerns regarding discontinuation rates and overall tolerability in curative-intent use.
  • Outcomes were influenced by a biologically enriched population, including adenocarcinoma histology and never-smokers.
  • Overall, the results of LIBRETTO-432 has practice-changing potential in a curative-intent setting and emphasizes the ongoing need for comprehensive genomic testing for early stage NSCLC.

2. Dual-Pathway Immunotherapy in Squamous NSCLC

  • Across ASCO 2026, increasing attention was given to the HARMONY-6 Phase 3 trial evaluating a bispecific antibody targeting immune checkpoint and VEGF pathways in advanced squamous NSCLC.
  • The study reflects growing momentum toward dual-mechanism immunotherapy approaches in historically difficult-to-treat disease.
  • HARMONY-6 demonstrated improved survival over PD-1 monotherapy with consistent benefit across biomarker subgroups, supporting VEGF inhibition as a potential immunotherapy enhancer to overcome immune heterogeneity that leads to lesser response in some patients.
  • Geographically concentrated enrollment and subgroup variability, including age-related differences, limit generalizability of this trial at this time.

3. AI in Thoracic Oncology

  • A dominant theme emerging from ASCO 2026 was the rapid expansion of artificial intelligence and machine learning into the clinical realm - reflecting a shift from conceptual tools to clinically deployable systems in pathology and diagnostics.
  • The Da Vinci study was highlighted as an example of deep learning integration into histopathologic workflows, built and validated on large-scale tissue datasets.
  • Da Vinci demonstrated strong diagnostic performance with near-immediate turnaround times, supporting use in time-sensitive intraoperative and procedural settings.
  • Investigators emphasized that the system is intended as an adjunct to, not a replacement for, pathologists.
  • Proposed applications include improving diagnostic efficiency, reducing inter-observer variability, and supporting rapid decision-making in settings without on-site pathology support.

4. Neoadjuvant Targeted Therapy in ALK-Positive NSCLC

  • ASCO 2026 featured robust discussion of the Phase 2 LORIN trial evaluating the use of Alectinib in the neoadjuvant setting for locally advanced ALK-positive NSCLC, highlighting its potential to expand surgical eligibility.
  • The study demonstrated substantial tumor downstaging prior to surgery, allowing for high rates of resection for borderline resection candidates while maintaining high rates of complete resection, often via minimally invasive approach.
  • Strong pathologic responses were observed at surgery, with consistent nodal downstaging, reinforcing the marked biologic sensitivity of ALK-driven tumors to targeted therapy in the neoadjuvant setting.
  • Limited regional recurrence was observed, primarily among patients who did not receive post-operative targeted therapy, raising questions regarding optimal perioperative sequencing and treatment duration.

5. Adaptive Oncology: Escalation and De-escalation Guided by Tumor Biology

  • The concept of adaptive oncology was a prominent topic across all cancer types at ASCO 2026, reflecting a shift toward real-time, biology-driven treatment optimization and response-guided decision-making.
  • The emphasis is moving away from traditional static treatment algorithms to dynamic strategies in which therapy is continuously adjusted based on early tumor response and biologic signals.
  • Pathologic response is maintaining its place as a key surrogate endpoint, with depth of response at surgery increasingly used to inform prognosis and guide downstream treatment decisions, reinforcing the role of tissue-based endpoints in modern trial design.
  • Patients with deep responses may be candidates for treatment de-escalation to reduce toxicity while maintaining disease control, supporting more individualized treatment duration.
  • Poor responders are increasingly identified as a high-risk group for treatment escalation or alternative strategies, aiming to avoid ineffective therapy and accelerate transition to novel approaches.

Main Points

  • Missing actionable alterations like EGFR, ALK, and now RET (via Libretto-432) deprives surgical patients of definitive survival advantages.
  • Potent pre-operative targeted agents (like lorlatinib in the LORIN trial) are consistently enhancing operability of locally advanced, borderline resectable tumors, allowing for minimally invasive, R0 resections.
  • Computational platforms like Da Vinci can analyze whole slide pathology imagery with pinpoint diagnostic accuracy in seconds, optimizing triage workflows.
  • The future belongs to response-guided therapies—using pathological residual tumor metrics to systematically escalate failing therapies or stop toxic treatments early.

Bottom Line

Findings from 2026 ASCO represent an era where the thoracic surgeon must act fundamentally as a thoracic oncologist. Surgical boundaries are no longer rigid anatomical limits; they are fluid metrics dictated by real-time biological data, multi-specific combinations, and pre-operative downstaging tools.

Ensuring flawless, early collaboration across multi-disciplinary clinic spaces is paramount to safely carrying high-risk mutational cohorts from systemic induction to the operating room and beyond.

“We are no longer simply looking at if we can operate, but how we creatively utilize team communication, tumor response data, and groundbreaking molecular tools to craft an adaptive pathway tailored specifically for that patient,” concluded Dr. Villena-Vargas.