A brave NEO world: Neoadjuvant osimertinib in resectable EGFR-mutant NSCLC

In a recent manuscript published in Lung Cancer, Chao et al reported the results of the phase IIb NEOS study [ [1] Lv C. Fang W. Wu N. Jiao W. Xu S. Ma H. Wang J. Wang R. Ji C. Li S. Wang Y. Yan S. Lu F. Pei Y. Liu Y. Yang Y. Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial. Lung Cancer. 2023; 178: 151-156https://doi.org/10.1016/j.lungcan.2023.02.011 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ]. This multicenter open label single arm study evaluated the efficacy of neoadjuvant osimertinib in patients with stage IIA-IIIB (TNM 8th edition) resectable EGFR-mutant non-small cell lung cancer (NSCLC) [ [2] M.B. Amin S.B. Edge F.L. Greene D.R. Byrd R.K. Brookland M.K. Washington J.E. Gershenwald C.C. Compton K.R. Hess D.C. Sullivan J.M. Jessup J.D. Brierley L.E. Gaspar R.L. Schilsky C.M. Balch D.P. Winchester E.A. Asare M. Madera D.M. Gress L.R. Meyer AJCC Cancer Staging Manual 2017 Springer International Publishing Cham. Google Scholar ]. The study demonstrated three key findings. First, of the 88 patients screened and 40 patients enrolled, 38 (95%) completed 6 weeks of planned neoadjuvant treatment with 71% (27/38) achieving an objective response (Fig. 1). Second, the study had favorable surgical outcomes, with 80% (32/40) of patients undergoing surgery of which 94% (30/32) achieved an R0 resection. These findings were supported by 40% of patients who underwent resection achieving nodal downstaging and 11% achieving a major pathologic response (MPR) (<10% viable tumor cells). Lastly, the neoadjuvant approach appeared safe and tolerable, with no adverse events (AEs) compromising time to surgery or surgical outcomes, and only 7.5% of the patients experiencing grade 3–4 AEs [ [3] Soria J.-C. Ohe Y. Vansteenkiste J. Reungwetwattana T. Chewaskulyong B. Lee K.H. Dechaphunkul A. Imamura F. Nogami N. Kurata T. Okamoto I. Zhou C. Cho B.C. Cheng Y. Cho E.K. Voon P.J. Planchard D. Su W.-C. Gray J.E. Lee S.-M. Hodge R. Marotti M. Rukazenkov Y. Ramalingam S.S. FLAURA Investigators, Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2018; 378: 113-125https://doi.org/10.1056/NEJMoa1713137 Crossref PubMed Scopus (2937) Google Scholar ]. NEOS provides an initial experience of neoadjuvant osimertinib in resectable EGFR-mutant NSCLC. These data show that it is a feasible and well-tolerated therapeutic strategy, resulting in favorable ORR and acceptable surgical outcomes. To place these data in context, we recently learned that the phase III ADAURA trial evaluating primary surgery followed by 3 years of adjuvant osimertinib in patients with early stage EGFR-mutant NSCLC, yields both a PFS and OS benefit- solidifying it as a standard of care in this population [ [4] Wu Y.-L. Tsuboi M. He J. John T. Grohe C. Majem M. Goldman J.W. Laktionov K. Kim S.-W. Kato T. Vu H.-V. Lu S. Lee K.-Y. Akewanlop C. Yu C.-J. de Marinis F. Bonanno L. Domine M. Shepherd F.A. Zeng L. Hodge R. Atasoy A. Rukazenkov Y. Herbst R.S. ADAURA Investigators, Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020; 383: 1711-1723https://doi.org/10.1056/NEJMoa2027071 Crossref PubMed Scopus (768) Google Scholar ]. The NEOS study proposes a neoadjuvant approach in the same setting and highlights potential benefits, such as the ability to measure objective response, fewer open surgeries, and other favorable surgical outcomes.