OBJECTIVE: Historically, standard of care for early-stage NSCLC was complete surgical resection, with adjuvant chemotherapy in resected stage II/III and select stage IB NSCLC. However, recurrence rates remained high, increasing with disease stage. Osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is approved as adjuvant therapy in pts with resected stage IB–IIIA EGFR mutated (EGFRm) NSCLC, having shown statistically significant and clinically meaningful disease-free survival (DFS) benefit in the Phase III ADAURA trial. Understanding real-world clinical outcomes in early-stage NSCLC will highlight the unmet needs in this population. We report interim results from a global non-interventional retrospective study of pts with resectable NSCLC using clinical data from medical records.
METHODS: Eligible pts (≥18 yrs) diagnosed with stage IA–IIIA NSCLC between Jan 1, 2014 and Dec 31, 2017 were followed to Dec 31, 2020. All pts had undergone complete resection and had EGFR test results available. Primary outcomes included EGFRm frequency, treatment patterns (including surgical type) and overall survival; DFS was an exploratory endpoint estimated by Kaplan-Meier at predefined landmark timepoints.
RESULTS: Of 463 pts from 6 countries (31% from Taiwan, 21% Canada, 17% US, 13% Austria, 10% South Korea, 9% France), median age was 66 yrs (range: 33–86); 427 pts (92%) had adenocarcinoma histology; 172 (37%) had stage IA NSCLC at initial diagnosis and 291 (63%) had stage IB–IIIA (22% IB, 13% IIA, 10% IIB, 18% IIIA). 213/463 pts (46%) were EGFRm of whom 99/213 (46%) were from Taiwan, 44 (21%) South Korea, 29 (14%) Austria, 18 (8%) Canada, 14 (7%) US, and 9 (4%) France. Stage at diagnosis (IA/IB/IIA/IIB/IIIA) for EGFRm and EGFRwt pts was 35/29/12/6/18% and 39/16/14/14/18%, respectively. Of first resections with margin status specified (n=342), 326 (95%) had R0 status. 49/463 pts (11%) had ≥2 resections; median time from diagnosis to first surgical resection was 0.6 (IQR 0.1–1.5) mo. Overall, lobectomy was the most common first resection procedure (video-assisted thoracoscopic surgery lobectomy, 244/463 [53%] and thoracotomy lobectomy, 144 [31%]); 62 (13%) had non-anatomical wedge resection, and surgical procedures by disease stage at diagnosis and country will be presented. In pts with EGFRm and EGFRwt NSCLC, 84/213 (39%) and 83/250 (33%), respectively, received neoadjuvant and/or adjuvant therapy, the majority of whom (156/167 pts [93%]) had stage IB–IIIA NSCLC. 106/156 pts (68%) had disease recurrence or death from time of surgery with similar proportions in pts with EGFRm (70%) and EGFRwt (66%) NSCLC. Sites of recurrence were also similar, most commonly lung and brain. Landmark DFS probabilities in EGFRm/EGFRwt groups were 72/77% at 12 mo and 29/32% at 60 mo, respectively.
CONCLUSION: In this real-world global study of surgically resected stage IA–IIIA NSCLC in pts who received an EGFR test, nearly half of the study cohort had EGFRm NSCLC, of whom 67% were treated in Taiwan/South Korea. Most resections had R0 margin status. DFS outcomes in pts with stage IB–IIIA NSCLC despite receiving (neo)adjuvant therapy reinforces the need for early diagnosis and EGFR testing to inform optimal treatment.
