Surgeons, Medical Oncologists, and Radiation Oncologists Debate Current Thresholds for Systemic Therapy in EGFR-Mutated NSCLC

During a recent OncLive® Scientific Interchange and Workshop held at the 2026 ASCO Annual Meeting, a multidisciplinary panel of Latin American thoracic surgeons, medical oncologists, and radiation oncologists worked through several case-based scenarios in EGFR-mutated non–small cell lung cancer (NSCLC) to examine where surgery, the ADAURA (NCT02511106) and NeoADAURA (NCT04351555) frameworks, and the LAURA (NCT03521154) chemoradiation-osimertinib (Tagrisso) pathway each fit as nodal burden increases.¹

The session, moderated by Narjust Florez, MD, FASCO, of Dana-Farber Cancer Institute; Paula Ugalde Figueroa, MD, of Brigham and Women's Hospital; and Francisco Javier Ruiz Lozano, MD, of Instituto Nacional de Cancerología, centered on the practical constraints of Latin American oncology practice, including molecular testing turnaround and access to radiation infrastructure.

Is EGFR-mutated NSCLC one disease across stages, or still stage-specific?

The panel opened by mapping the EGFR-mutated NSCLC treatment continuum across five phase 3 trials:^2-6

• NeoADAURA: neoadjuvant osimertinib plus chemotherapy, then surgery, then adjuvant osimertinib, in resectable stage II to IIIA disease
  • Major pathologic response rate was 26% (95% CI, 18%-34%) in the combination arm (n = 121) vs 2% (95% CI, 0%-6%) with placebo plus chemotherapy (n = 120; OR, 19.28; 99.9% CI, 1.71-217.39; P < .0001);
• ADAURA: adjuvant osimertinib in stage IB to IIIA disease
  • Significant reduction in disease-free survival risk vs placebo in stage II to IIIA disease (overall HR for disease recurrence or death, 0.17; 99.06% CI, 0.11-0.26; P < .001;
• LAURA: osimertinib after chemoradiation in unresectable stage III disease
  • Median progression-free survival (PFS), 39.1 months vs 5.6 months with placebo (HR, 0.16; 95% CI, 0.10- 0.24; P < .001);
• FLAURA (NCT02296125): first-line osimertinib in EGFR exon 19 deletion- or L858R-positive metastatic disease
  • Median PFS, 18.9 months vs 10.2 months with standard EGFR TKIs (HR, 0.46; 95% CI, 0.37-0.57; P < .001); and
• FLAURA2 (NCT04035486): osimertinib plus platinum-doublet chemotherapy in first-line metastatic disease
  • Median PFS, 25.5 months vs 16.7 months with osimertinib alone (HR, 0.62; 95% CI, 0.49-0.79; P < .001).

This question of whether EGFR-mutated NSCLC now functions as one biological entity treated along a continuum, or remains several stage-specific diseases anchored both case discussions that followed.¹

How should single-station N2 disease be sequenced?

The first case centered on a 61-year-old never-smoker with ECOG performance status of 1, a 3.4-cm right upper lobe mass, EBUS-confirmed single-station N2 disease at station 4R, an EGFR exon 19 deletion, and PD-L1 expression level of 90%. Participants agreed that this is one of the most clinically uncertain scenarios in current thoracic oncology, a patient who in 2020 would have gone straight to surgery and adjuvant osimertinib per ADAURA, but for whom evolving data from NeoADAURA now create meaningful alternatives.

Ugalde Figueroa walked the group through ADAURA’s design limitations, noting it enrolled patients predominantly from Asia, used 7th-edition TNM staging, and randomly assigned patients only after surgery, leaving preoperative sequencing unanswered. “[It’s important to read the details of] NeoADAURA. The highest pathological response rate was seen in patients who received osimertinib plus chemotherapy or osimertinib alone. Do you remember the numbers? Twenty-six percent and 25%. Osimertinib is driving the response…chemotherapy alone is not driving the response,” Ugalde Figueroa said.

A recurring theme was molecular testing turnaround: comprehensive next-generation sequencing [NGS] results take 3 to 5 weeks across most Latin American centers, prompting reliance on smaller targeted panels for EGFR, ALK, ROS1, and PD-L1 by immunohistochemistry, with 7- to 10-day turnaround instead. Lozano Ruiz asked the room directly, “Who among you can get an NGS result in less than 3 weeks?” One participant answered, “No one. In Latin America, no one.” Florez separately cautioned against treating PD-L1 positivity as a trigger for chemoimmunotherapy in this population. “So, the point is, chemotherapy, yes, but don’t give them immunotherapy, because then we’re going to have problems in the end.”

Does increasing nodal burden shift the threshold toward LAURA?

The panel modified the case to nonbulky, three-station biopsy-proven N2 disease that remained technically resectable after multidisciplinary review, and discussion shifted noticeably toward chemoradiation. Asked whether the number of involved N2 stations mattered independent of nodal size, Ugalde Figueroa probed the group: “Who thinks this patient is a candidate for surgery? Is the number of N2 lymph nodes important to you? Not the size of the lymph nodes, but the number. He has 3 positive lymph node stations.” Lozano Ruiz reframed the decision around comparable survival between pathways: “LAURA offers 40 months [of median PFS], which is practically the same for both strategies... but as everyone has said, the 2 strategies haven’t been directly compared. The patient will likely experience a systemic relapse; we agree on that. The key player here is osimertinib.” He added that resource access, not just biology, drove sequencing. “Surgery may sometimes be available in 3 months, while other times we can get it done within a month. The same applies to radiation therapy... so, in addition to the patient’s age, I would also factor in access times and treatment availability.”

Why did the panel reach near-unanimous agreement on N3 disease?

The second case involved a 56-year-old Hispanic woman, never-smoker, with biopsy-confirmed lung adenocarcinoma, 4L EBUS-confirmed N3 disease, an EGFR exon 19 deletion, PD-L1 expression of 10%, and a negative brain MRI. Florez was unequivocal that upfront surgery has no role here, characterizing stage IIIB EGFR-mutated disease as inherently systemic. “What is a stage IIIB tumor? It’s a stage IV tumor that’s 3 weeks away from declaring itself... So, I am a strong advocate of indefinite osimertinib... before PACIFIC [NCT02125461], which is the relevant historical comparison here, [approximately] 75% to 80% of these patients would recur as stage IV disease after chemoradiation. So, for me, it’s osimertinib until something happens.”

On timing of osimertinib initiation after chemoradiation, Lozano Ruiz explained the 6- to 8-week restaging window most panelists favored. “We normally do it 6 to 8 weeks after completing radiation therapy... it allows us to assess response, evaluate the results of treatment, and determine how the patient is doing in terms of toxicity.” He cited radiation pneumonitis as the central toxicity concern when layering osimertinib onto prior thoracic irradiation, advocating for breath-hold delivery and image-guided radiation therapy despite the operational cost. “A treatment that would normally take 5 minutes may now take 20 to 25 minutes when performed with breath-hold... the dose-volume histograms improve substantially.” The 3-year vs indefinite duration of therapy question per LAURA remains debated, compounded by limited Latin American access to circulating tumor DNA/minimal residual disease testing that could help personalize duration.

What are the unmet needs going forward?

The panel converged on 3 priorities: expanding access to timely comprehensive molecular testing in early- and locally advanced-stage disease, accelerating regulatory and formulary pathways for osimertinib across the full stage continuum, and building functioning multidisciplinary tumor boards—inclusive of radiation oncology—at the point of initial patient evaluation. Ugalde Figueroa underscored the entry-point problem motivating this last priority: “First, the surgeon, and that’s a key point. Because if surgeons aren’t part of a multidisciplinary team, no one is going to order the molecular testing.”

References

1. Advancing care in EGFR-mutated NSCLC: a case-based workshop for Latin American oncology practice. An OncLive Scientific Interchange and Workshop. OncLive. May 29, 2026. Accessed June 30, 2026.
2. He J, Tsuboi M, Weder W, et al. Neoadjuvant osimertinib for resectable EGFR-mutated non–small cell lung cancer. J Clin Oncol. 2025;43(26):2875-2887. doi:10.1200/JCO-25-00883
3. Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. doi:10.1056/NEJMoa2027071
4. Lu S, Kato T, Dong X, et al. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597. doi:10.1056/NEJMoa2402614
5. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. doi:10.1056/NEJMoa1713137
6. Planchard D, Janne PA, Cheng Y, et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434