Until recently, limited data were available on the neoadjuvant use of osimertinib in patients with resectable, EGFR-mutated non-small cell lung cancer (NSCLC). As presented at ELCC 2022, the phase II NEOS study demonstrated promising efficacy and tolerability of neoadjuvant osimertinib. Objective response rates and disease control rates with neoadjuvant osimertinib were high, with nearly half of the patients achieving a pathological response of more than 50%.
Recent evidence has demonstrated that the neoadjuvant use of first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) may provide clinically meaningful improvements in EGFR-mutated non-small cell lung cancer (NSCLC) patients. However, limited data were reported on osimertinib in the neoadjuvant setting. The NEOS study is a multicentre, single-arm, phase II study to evaluate the efficacy and safety of osimertinib as neoadjuvant treatment in resectable EGFR-mutated lung adenocarcinoma. Previously, the interim analysis of the NEOS study has demonstrated the promising efficacy and tolerable safety profile of neoadjuvant osimertinib in patients with resectable EGFR-mutated NSCLC. At ELCC 2022, an updated analysis of neoadjuvant osimertinib was presented.
Eligible patients aged 18-75 years with resectable, stage II-IIIB (T3-4N2), EGFR-mutated lung adenocarcinoma were enrolled and treated with osimertinib (80 mg, once daily) for six weeks, followed by surgical resection. The primary endpoint was objective response rate assessed by investigator per RECIST v1.1 criteria. The secondary endpoints included safety, R0 resection rate, quality of life, major pathologic response (MPR) rate, pathological complete response (pCR) rate, and N2 downstaging rate.
Between October 17, 2018 and June 8, 2021, 88 patients were screened and 44 patients were successfully enrolled. Of them, 38 completed the six-week neoadjuvant osimertinib and 32 patients received surgical resection (50% video-/robot-assisted thoracoscopic surgery; 50% open thoracotomy). R0 was achieved in 30 resected patients (94%). Median age of study participants was 63 years, 37.5% were male and 70% were never smokers. Half of the patients had an exon 19 deletion while the other half had an exon 21 L858R mutation. The objective response rate was 71.1% and the disease control rate was 100%. Of the pathological evaluable patients, 11% (3/28) achieved a major pathological response, including one pathological complete response (pCR). Furthermore, thirteen patients (46%) had a pathological response of at least 50%.
During neoadjuvant treatment, treatment-related adverse events (TRAEs) were reported in 75% of patients. The most common events were rash (50%), diarrhoea (30%), oral ulcerations (30%), dry skin (13%), decreased appetite (10%) and fatigue (10%). No adverse event led to neoadjuvant treatment discontinuation. Three patients (7.5%) had TRAES of grade 3, including rash, hypertension and renal disease, respectively. Perioperative complications occurred in three patients, including one patient with fatal respiratory failure and the other two patients with deep vein or pulmonary thrombosis and subcutaneous emphysema, respectively. Both recovered during perioperative care.
The phase II NEOS study demonstrated the promising efficacy and tolerability of neoadjuvant osimertinib. Nearly half of the patients had a pathological response of higher than 50%, including one patient who achieved pCR. The safety profile of osimertinib in the neoadjuvant setting remains generally consistent with the previous reports. No adverse events led to treatment discontinuation. Phase III trials including a larger number of patients are warranted to further validate the benefit of osimertinib in the neoadjuvant setting.
Lyo Chao, et al. Osimertinib as neoadjuvant therapy in patients with EGFR mutated resectable stage II-IIIB lung adenocarcinoma (NEOS): Updated Results. Presented at ELCC 2022; Abstract 81MO.