2026 Cancer Updates GI and Lung Denver: Lung Cancer Updates and Panel Discussion
Presenter:
Tejas Patil, MD, University of Colorado
Discussion Panelists:
Tejas Patil, MD, University of Colorado (Moderator)
Urs Weber, MD, University of Colorado
Kyle Concannon, MD, University of Colorado
Eric Bernicker, MD, FASCO, CommonSpirit Health
Overview
At the 2026 Cancer Updates GI and Lung dinner program in Denver Colorado, Dr Tejas Patil’s presentation highlighted several of the most rapidly evolving areas in thoracic oncology, with a focus on perioperative immunotherapy and integration of circulating tumor DNA (ctDNA) strategies, HER2-altered non–small cell lung cancer (NSCLC), and relapsed/refractory small cell lung cancer (SCLC). Across these domains, Dr Patil’s discussion emphasized not only some of the most recent clinical trial data, but also the increasingly complex decision-making required to integrate new therapies into practice.
A consistent theme throughout both the presentation and subsequent panel discussion was the shift toward adaptive and biomarker-informed treatment strategies, particularly the emerging role of ctDNA in guiding escalation and de-escalation decisions. At the same time, Dr Patil and the panel underscored the practical realities of implementation, including access disparities, toxicity management, and gaps in prospective data.
Advances in Perioperative Therapy and ctDNA Monitoring
Dr Patil began by revisiting the evolution of treatment for resectable NSCLC, noting how the field has rapidly transitioned from a relatively simple paradigm of surgery followed by adjuvant chemotherapy to a far more nuanced approach incorporating neoadjuvant and perioperative immunotherapy. He noted trials such as CheckMate 816 which have fundamentally reshaped the treatment landscape, demonstrating that the addition of immune checkpoint inhibition (ICI) to chemotherapy in the neoadjuvant setting significantly improves outcomes.
One of the most striking shifts he noted has been the emergence of pathologic complete response (pCR) as a meaningful clinical endpoint. Historically, pCR rates with neoadjuvant chemotherapy alone were low, often in the range of 2% to 12%, and were not widely considered a reliable surrogate for long-term outcomes. The integration of immunotherapy, however, has dramatically increased pCR rates, with CheckMate 816 for example demonstrating a pCR rate of approximately 24% compared with just over 2% with chemotherapy alone. As such, Dr Patil emphasized that pCR is no longer simply a descriptive metric but one that may have prognostic significance. Data from CheckMate 816 and subsequent perioperative trials suggest that patients who achieve a pCR experience substantially improved event-free survival, raising the possibility that pCR could be used to guide downstream treatment decisions.
This discussion led to one of the more forward-looking components of Dr Patil’s presentation – the emerging role of ctDNA as a dynamic biomarker. He noted early data, including analyses from perioperative trials such as AEGEAN, which suggest that ctDNA clearance prior to surgery correlates with both pCR and improved outcomes, positioning ctDNA as a potential tool for real-time treatment adaptation. Dr Patil framed this as an emerging paradigm shift with the question “What is the relationship between ctDNA clearance and how do we integrate that into making decisions in an adaptive way… in the adjuvant setting?”
The subsequent panel discussion expanded on this concept, focusing on the potential for ctDNA to enable treatment de-escalation in low-risk patients and escalation in high-risk patients. One panelist described this as opening a “Pandora’s box,” of sorts, reflecting both the promise and uncertainty of integrating highly sensitive molecular monitoring into clinical workflows. At the same time, the panel emphasized important caveats. ctDNA positivity in the absence of radiographic disease progression, for example, introduces significant clinical ambiguity and patient anxiety, particularly given the lack of standardized management strategies. As one panelist noted, the field is still grappling with whether early detection of a molecular recurrence translates into actual improved outcomes or simply the possibility for earlier intervention without survival benefit.
Advances in First-Line HER2-Altered NSCLC
The second major focus of Dr Patil’s presentation was the rapidly evolving treatment landscape for HER2-altered NSCLC, a relatively rare but increasingly actionable subset of lung cancer. He noted HER2 alterations, including exon 20 insertion mutations, gene amplification, and protein overexpression, as collectively accounting for approximately 3% to 4% of NSCLC cases. Dr Patil also highlighted the complexity of this space, noting that different forms of HER2 alteration may not behave identically or respond uniformly to targeted therapies. He reviewed the therapeutic landscape, which now includes both antibody-drug conjugates (ADCs) and small-molecule tyrosine kinase inhibitors (TKIs), creating new challenges around treatment selection and sequencing.
Dr Patil noted trastuzumab deruxtecan (T-DXd), evaluated in the DESTINY-Lung02 trial, which has been established as an effective option in previously treated HER2-mutant NSCLC, demonstrating an objective response rate (ORR) of approximately 49% and a disease control rate exceeding 90%. He emphasized, however, the importance of toxicity considerations, particularly interstitial lung disease (ILD), which appears to contribute to treatment discontinuation and may influence progression-free survival (PFS) interpretations.
Dr Patil’s discussion then turned to HER2-targeted TKIs, particularly zongertinib, which has generated significant enthusiasm based on early-phase data. In the Beamion LUNG-1 study, zongertinib demonstrated an ORR of approximately 70%, along with meaningful intracranial activity, which is an important consideration in NSCLC. Dr Patil noted that this level of efficacy has led to rapid regulatory movement, including approval in the frontline setting, marking a significant shift in how HER2-mutant NSCLC may be treated. Importantly, Dr Patil noted that toxicity profiles differ substantially between ADCs and TKIs, with zongertinib showing a more typical TKI-associated profile dominated by diarrhea and rash, and relatively low discontinuation rates.
The subsequent panel discussion highlighted the growing complexity of treatment decision-making in the HER2-altered space, particularly in the absence of head-to-head comparisons. As such, clinicians are now faced with multiple viable first-line options, including chemotherapy-based regimens, ADCs, and TKIs. As one panelist noted, this represents a “glorious situation” compared with earlier eras of limited options but also introduces much uncertainty in relation to the optimal sequencing of therapies. In this regard, patient preference is expected to play a major role, particularly given the appeal of oral therapies. At the same time, the panel noted that clinicians must weigh factors such as disease burden, CNS involvement, and toxicity profiles. The panel further emphasized that biomarker testing remains a critical bottleneck, with ongoing underutilization of comprehensive genomic profiling in real-world practice, limiting the identification of actionable mutations.
Advances in Relapsed/Refractory Small Cell Lung Cancer
The final section of Dr Patil’s presentation focused on relapsed and refractory SCLC, an area that has historically seen limited therapeutic progress. Dr Patil highlighted two key advances - the IMforte trial, evaluating maintenance lurbinectedin, and the DeLLphi-304 trial evaluating tarlatamab, a DLL3-targeted T-cell engager.
The IMforte study demonstrated an overall survival benefit for the addition of lurbinectedin to maintenance atezolizumab following first-line chemoimmunotherapy, with median survival of 13.2 months versus 10.6 months; however, Dr Patil urged caution in interpreting these results, noting that the study population was highly selected, excluding patients with brain metastases or poor performance status. Additionally, relatively few patients in the control arm had received lurbinectedin at progression, raising questions about whether the observed benefit reflects earlier use of an effective agent rather than a true maintenance effect. This led to a broader discussion about whether IMforte represents maintenance therapy or simply front-loading second-line treatment, an important conceptual distinction for clinical practice.
In contrast, the DeLLphi-304 trial evaluating tarlatamab represents a more definitive advance in the second-line setting. Tarlatamab is a bispecific T-cell engager targeting DLL3, a protein highly expressed in SCLC. The study demonstrated a significant overall survival benefit compared with standard chemotherapy, with a 12-month survival rate of approximately 53% - a notable improvement in a disease where second-line options have historically been limited. Dr Patil emphasized the broader significance of this finding: “This is the first second-line study that has shown anything better than topotecan… we should just pause and reflect at that reality.” While response rates were modestly improved, the durability of response and emerging plateau in survival curves suggest the potential for longer-term benefit in a subset of patients, reminiscent of patterns seen with immunotherapy in NSCLC. Dr Patil also noted that tarlatamab introduces a distinct toxicity profile, including cytokine release syndrome (CRS) and dysgeusia, with the latter likely related to DLL3 expression in taste buds. He noted that these adverse events require specialized management and infrastructure, which has important implications for real-world implementation.
Panel Discussion: Real-World Implementation
The panel discussion provided critical insight into how these advances are being translated into practice. A central theme was the challenge of integrating novel therapies into diverse care settings, particularly given disparities in access. For example, while it was acknowledged that tarlatamab represents a meaningful advance, its administration requires experience in managing CRS and immune-related toxicities, often limiting its availability to larger academic centers. One panelist noted that patients in rural settings may face significant barriers to accessing such therapies, highlighting the need for more equitable distribution of resources.
Similarly, the discussion of ctDNA underscored the tension between technological capability and clinical readiness. While tumor-informed assays offer highly sensitive detection of minimal residual disease, it was noted that a lack of standardized management pathways creates uncertainty for both clinicians and patients. The panel emphasized the importance of shared decision-making, particularly in situations where ctDNA results may influence surveillance intensity or trigger additional interventions without clear evidence of benefit.
Treatment Sequencing and Ongoing Clinical Questions
Across all three domains, several key unanswered questions emerged. In perioperative NSCLC, the optimal duration and necessity of adjuvant immunotherapy in patients achieving pCR remain unclear, particularly as ctDNA-guided strategies are explored. In HER2-altered NSCLC, the lack of comparative data between ADCs and TKIs complicates first-line treatment selection, while sequencing strategies remain undefined.
In SCLC, questions persist regarding the optimal integration of maintenance therapies and the positioning of tarlatamab earlier in the treatment course. Ongoing trials exploring combination approaches and earlier-line use of T-cell engagers are likely to further reshape the landscape.
Conclusions and Clinical Implications
Dr Patil’s lung cancer update highlighted a period of rapid innovation in lung cancer, characterized by the convergence of targeted therapy, immunotherapy, and biomarker-driven decision-making. The integration of perioperative immunotherapy has redefined expectations in early-stage NSCLC, while advances in HER2-targeted therapy are expanding options in a previously underserved molecular subset. In SCLC, the emergence of tarlatamab represents a long-awaited step forward in the relapsed setting.
At the same time, these advances introduce new complexities related to treatment selection, sequencing, and toxicity management. The incorporation of ctDNA into clinical decision-making holds significant promise but will require prospective validation and thoughtful integration into care pathways.
Speaker Disclosure Information: Dr Patil reported the following disclosures for this presentation: Advisory Role (advisory boards or consultations) in last 3 years: Aadi Biosciences, Astrazeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Caris, Cellworks, Daiichi, Erasca, Foundation Medicine, Guardant Health, Gilead, Johnson & Johnson, Jazz Pharmaceuticals, Merus, Natera, Nuvalent, Nuvation, Pfizer, Regeneron, Rigel, Roche/Genentech, Summit Therapeutics, Takeda; DSMB or Scientific Steering Committees: Boehringer Ingelheim, Johnson & Johnson, Eli Lilly; Research Funding: Janssen, Gilead
