NeoADAURA is a phase III clinical trial assessing osimertinib ± Pt-ChT vs Pt-ChT alone in the neoadjuvant setting. Eligible patients must have non-squamous, completely resectable stage II–IIB N2 NSCLC and an EGFR exon 19 deletion or L858R substitution mutation, either alone or in combination with other EGFR mutations.¹ While NCCN guidelines recommend patients with stage IIB NSCLC are evaluated for perioperative therapy, an EGFR exon 19 deletion or exon 21 L858R substitution is considered a contraindication to neoadjuvant PD-1/PD-L1 inhibition.² Subgroup data from the AEGEAN trial showed that patients with an EGFR mutation derived less benefit from perioperative durvalumab than those without EGFR/ALK aberrations.³ CheckMate 816 excluded patients with EGFR/ALK aberrations.⁴ NAUTIKA1 is a phase II clinical trial assessing the efficacy and safety of neoadjuvant alectinib (ALK cohort), entrectinib (ROS 1 and NTRK cohorts), pralsetinib (RET cohort) and atezolizumab (PD-L1 ≥1% cohort) in untreated patients with stage IB–IIIA, or selected IIIB, resectable NSCLC.⁵

Abbreviations
ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; NCCN, National Comprehensive Cancer Network®; NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; PD-1, programmed cell death protein 1; PD-L1, programmed death ligand-1; Pt-ChT, platinum-based chemotherapy; RET, ret proto-oncogene; ROS1, ROS proto-oncogene 1.

References

1. ClinicalTrials.gov. NCT04351555. Available at: https://clinicaltrials.gov/study/NCT04351555 (accessed 20 September 2024).
2. NCCN Clinical Practice Guidelines in Oncology. NSCLC Version 9.2024 — September 9, 2024. Available at: NCCN.org (accessed 13 September 2024).
3. He J, et al. J Thorac Oncol. 2023;18(Suppl.):S72–3.
4. Spicer J, et al. J Clin Oncol. 2024;42(Suppl. 17):LBA8010.
5. ClinicalTrials.gov. NCT04302025. Available at: https://clinicaltrials.gov/study/NCT04302025 (accessed 1 October 2024).

The LAURA trial assessed the efficacy and safety of osimertinib vs placebo in patients with unresectable stage III EGFR-mutant (exon 19 deletion or exon 21 L858R substitution) NSCLC, without disease progression during or after concurrent or sequential platinum-based chemoradiotherapy within 6 weeks before undergoing randomization. Any-grade adverse events grouped as radiation pneumonitis were reported in 68 patients (48%) treated with osimertinib, of which 3 (2%) were grade 3, and 28 patients (38%) who received placebo, all of which were grade 1 or 2. The median PFS was 39.1 months with osimertinib and 5.6 months with placebo (hazard ratio for disease progression or death, 0.16; 95% CI 0.10–0.24; p<0.001).

Abbreviations
CI, confidence interval; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; PFS, progression-free survival.

Reference
Lu S, et al. N Engl J Med. 2024;391:585–97.

Biomarker testing is not well defined in treatment guidelines and currently not routine in all countries or treatment centres.¹ ESMO guidelines state that, for early and locally advanced NSCLC, EGFR mutational status is mandatory and EGFR fusion status is optional; PD-L1 expression is mandatory for unresectable disease and optional for completely resectable disease.² NCCN guidelines state that PD-L1, EGFR mutations and ALK rearrangements should be assessed in stages IB–IIIA and IIIB (T3, N2) prior to neoadjuvant systemic treatment.³ However, despite guideline recommendations, a recent survey showed that 43% of HCPs across 14 disciplines said they sometimes or often treat patients prior to receiving the biomarker results and 29% ranked comprehensive biomarker testing as highly important in early-stage disease (vs 63% in late-stage disease).⁴

Abbreviations
ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; ESMO, European Society for Medical Oncology; HCP, healthcare professionals; NCCN, National Comprehensive Cancer Network®; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1.

References

1. Kato T, et al. Lung Cancer. 2024;187;107144.
2. ESMO. Lung & Chest Cancers Pocket Guideline 2023. Available at: https://bit.ly/3pRPTDp (accessed 1 October 2024);
3. NCCN Clinical Practice Guidelines in Oncology. NSCLC Version 9.2024 — September 9, 2024. Available at: NCCN.org (accessed 13 September 2024).
4. Smeltzer M, et al. Presented at: WCLC 2024. San Diego, CA, USA. 7–10 September 2024. OA03.03.

Due to disease heterogeneity and the multimodality of potential treatments for patients with stage III NSCLC, the MDT, comprising thoracic surgeons, radiation and medical oncologists, pulmonologists, pathologists and others, plays a crucial role in accurate staging, resectability assessment, tumour biomarker testing and tailoring treatment.¹ International guidelines state that disease staging, resectability and treatment choice should be determined upfront by an MDT.^2–4 Neoadjuvant therapy should not be used to attempt to induce resectability in patients who do not already meet criteria for resectability on initial evaluation.⁴

Abbreviations
MDT, multidisciplinary team; NSCLC, non-small cell lung cancer.

References

1. Kato T, et al. Lung Cancer. 2024;184:107414.
2. Park K, et al. Ann Oncol. 2020;31:191–201.
3. Daly ME, et al. J Clin Oncol. 2022;40:1356–84.
4. NCCN Clinical Practice Guidelines in Oncology. NSCLC Version 9.2024 — September 9, 2024. Available at: NCCN.org (accessed 13 September 2024).