Erlotinib as Neoadjuvant Therapy in Stage IIIA (N2) EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Prospective, Single-Arm, Phase II Study.

LESSONS LEARNED: The findings of this prospective, single-arm, phase II study showed that neoadjuvant erlotinib was well tolerated and might improve the radical resection rate in patients with stage IIIA-N2 epidermal growth factor receptor mutation-positive non-small cell lung cancer (NSCLC).Erlotinib shows promise as a neoadjuvant therapy option in this patient population.Next-generation sequencing may be useful for predicting outcomes with preoperative tyrosine kinase inhibitors (TKIs) in patients with NSCLC.Large-scale randomized controlled trials investigating the role of TKIs in perioperative therapy, combining neoadjuvant and adjuvant treatments to enhance personalized therapy for patients in this precision medicine era, are warranted. BACKGROUND: Information on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as neoadjuvant therapy in non-small cell lung cancer (NSCLC) is scarce. We evaluated whether neoadjuvant erlotinib improves operability and survival in patients with stage IIIA-N2 EGFR mutation-positive NSCLC. METHODS: We conducted a prospective, single-arm, phase II study. Patients received erlotinib 150 mg per day for 56 days in the neoadjuvant period. The primary endpoint was the radical resection rate. RESULTS: Nineteen patients were included in the final analysis. After erlotinib treatment, 14 patients underwent surgery. The radical resection rate was 68.4% (13/19) with a 21.1% (4/19) rate of pathological downstaging. The objective response rate was 42.1%; 89.5% (17/19) of patients achieved disease control, with a 10.3-month median disease-free survival among patients who underwent surgery. Among all 19 patients who received neoadjuvant therapy, median progression-free survival (PFS) and overall survival were 11.2 and 51.6 months, respectively. Adverse events (AEs) occurred in 36.8% (7/19) of patients, with the most common AE being rash (26.3%); 15.8% experienced grade 3/4 AEs. Quality of life (QoL) improvements were observed after treatment with erlotinib for almost all QoL assessments. Effects of TP53 mutation on prognosis were evaluated in eight patients with adequate tissue samples. Next-generation sequencing revealed that most patients had a TP53 gene mutation (7/8) in addition to an EGFR mutation. No TP53 mutation, or very low abundance, was associated with longer PFS (36 and 38 months, respectively), whereas high abundance was associated with short PFS (8 months). CONCLUSION: Neoadjuvant erlotinib was well tolerated and may improve the radical resection rate in this patient population. Next-generation sequencing may predict outcomes with preoperative TKIs.

Surgical techniques for early-stage thymoma: video-assisted thoracoscopic thymectomy versus transsternal thymectomy.

OBJECTIVE: The present study compared the outcomes between patients who had undergone video-assisted thoracoscopic surgery (VATS) thymectomy and transsternal (TS) thymectomy for Masaoka stage I and II thymoma. METHODS: The outcomes of 262 patients without myasthenia gravis who had undergone surgery for Masaoka stage I and II thymoma from January 2008 to December 2012 at our center were retrospectively evaluated. The study included 125 patients who had undergone unilateral VATS thymectomy (VATS group) and 137 patients who had undergone TS thymectomy (TS group). RESULTS: The VATS group had a shorter operative time than the TS group (170 vs 210 minutes, P < .001). The VATS group also had a smaller intraoperative blood loss (200 vs 450 mL, P < .001), smaller pleural drainage volume in the first 24 hours postoperatively (300 vs 500 mL, P < .0010), shorter postoperative pleural drainage duration (3 vs 5 days, P < .001), and shorter postoperative hospital stay (8 vs 10 days, P < .001). Four patients in the VATS group underwent conversion to open surgery because of injury to the innominate vein. The postoperative complication rate was similar between the 2 groups. One patient in the VATS group developed pleural recurrence, and one in the TS group developed local recurrence. CONCLUSIONS: Unilateral VATS thymectomy for Masaoka stage I and II thymoma is technically feasible and safe and is less invasive than TS thymectomy, with a shorter duration of surgery, less intraoperative blood loss, less postoperative pleural drainage, shorter postoperative pleural drainage duration, and shorter postoperative hospital stay. We have concluded that it is preferable to perform VATS thymectomy, although perhaps under certain circumstances sternotomy might be preferred. The oncologic outcomes were comparable between the 2 procedures. Additional follow-up is required to evaluate the long-term outcomes.