The efficacy and safety of the neoadjuvant therapy of osimertinib are gratifying.
From March 30 to April 2, 2022, the European Lung Cancer Conference (ELCC) was held online. The results of the NEOS study of osimtinib for the resectable neoadjuvant therapy of stage II-IIIB EGFR mutation resectable lung adenocarcinoma carried out by the team of Professor Yang Yue of Peking University Cancer Hospital were published in the form of a mini oral report (81MO), which was shared by Professor Lv Chao of Peking University Cancer Hospital. Studies have shown that the objective response rate (ORR) of neoadjuvant therapy of osimtinib is 71.1%, the resection rate of R0 is 94%, the pathological response rate of 46% of patients is ≥ 50%, and the safety is consistent with the results of previous osimitinib studies.
In this regard, the Medical Oncology Channel invited Professor Lv Chao to share the updated highlights of the research results and their clinical significance, and invited Professor Yang Yue to look forward to the application prospects of new adjuvant targeted therapy.
The largest three-generation EGFR-TKI neoadjuvant treatment data to date: R0 resection rate of up to 94%, greatly improving the efficacy of surgery
NEOS is a prospective, multicenter, single-arm, phase II study to evaluate the efficacy and safety of osimertinib as a neoadjuvant treatment regimen in resectable EGFR mutation (19del/L858R) lung adenocarcinoma. Eligible 18- to 75-year-olds were included in eligible patients with resectable, stage II-IIIB (T3-4N2), EGFR-mutated lung adenocarcinoma who received osimertinib 80 mg once daily for six weeks followed by surgical resection. The primary endpoint was the ORR assessed by the investigators according to RECIST v 1.1. Secondary endpoints included safety, R0 resection rate, quality of life, primary pathological response (MPR) rate, pathological complete response (pCR) rate, and N2 descent rate.
The interim results of the NEOS study, presented at the 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO), initially confirm the benefits of the neoadjuvant therapy with osimtinib, but the data are not yet mature. Professor Lv Chao introduced that compared with the interim analysis, the number of patients included in this analysis is larger, and the tumor remission data such as ORR and MPR rate are updated, and the occurrence of adverse events (AE) such as medication complications and perioperative complications is elaborated.
From October 17, 2018 to June 8, 2021, the study screened a total of 88 patients and finally enrolled 40 patients. Among the 38 patients who completed oxetinib neoadjuvant therapy at 6 weeks, the ORR was 71.1% (27/38), and the disease control rate reached 100%, which meant that no patients had disease progression during neoadjuvant therapy, and 71.1% of patients had significant tumor reduction, creating opportunities for subsequent reduction of surgical resection range, reduction of the difficulty of surgical resection, and improvement of surgical efficacy.
In addition, of the 28 pathologically evaluable patients, 11% achieved MPR, and 1 (4%) of them achieved pCR. Pathological response was 50%≥ in 46% (13 patients), meaning that about half of patients had fewer than 50% of residual tumor cells after neoadjuvant therapy.
Professor Lu Chao said: "From a surgical point of view, we attach great importance to ORR. Because of the higher ORR, it means that neoadjuvant therapy can significantly reduce the tumor volume and improve the R0 resection rate. For patients with stage II-III, surgical resection is a very critical step, and whether R0 resection can be achieved is closely related to prognosis. ”
In the study, 32 patients underwent surgery, of which 50% were video/robot-assisted thoracoscopic surgery, 50% were open surgery, and 94% (30 cases) of patients had R0 resection. "The R0 resection rate after neoadjuvant therapy of the first and second generation EGFR-TKI in the past is about 60%-80%. Neos studies included a large number of patients with heavy tumor load, late disease and other difficult surgery, and the R0 resection rate of osimertinib can still reach 94% after neoadjuvant therapy, which is quite good. ”
This study reports data on neoadjuvant therapy in the largest prospective population to date.
Good safety, does not affect surgery and does not increase perioperative complications
Clinical treatment has always attached equal importance to efficacy and safety. Neos studies have shown that adjuvant therapy with ositinib has good safety and tolerability without significantly increasing perioperative complications.
Professor Lu Chao introduced that the AE of adjuvant therapy for oscitinib in neos research is consistent with previous reports, mainly for rashes, diarrhea and mouth ulcers. Overall, patients tolerated well and did not affect treatment, with no patients taking doses or discontinuing AE. Problems such as adhesions, fibrosis, intraoperative or postoperative bleeding, prolonged hospital stay were not observed.
"Overall, neoadjuvant targeted therapies are relatively safe, especially osimertinib." Professor Lu Chao said.
Future can be expected: Ositinib perioperative full treatment mode to help prolong survival
"A previous retrospective study conducted by us found that for patients with better efficacy of neoadjuvant targeted therapy, patients had a very high recurrence rate if adjuvant chemotherapy was used or if adjuvant therapy was not given after surgery. Therefore, for patients with neoadjuvant targeted therapy, the postoperative treatment model of ADAURA research is often followed, and patients are given adjuvant targeted therapy. Professor Lu Chao said, "Although the intermediate disease-free survival period (DFS) of the osimertinib group in the ADAURA study has not yet been achieved, the patient's DFS should be very long under the perioperative full-course treatment mode of neoadjuvant + adjuvant therapy." ”
Professor Lu Chao said: "At present, in many centers, for local advanced lung cancer, neoadjuvant therapy has gradually become a commonly used method. With the publication of the NEOS study results, neoadjuvant targeted therapy may become a future trend for patients with EGFR mutations. First of all, neoadjuvant targeted therapy is relatively safe, especially single-drug targeted therapy, which can achieve 'chemo free', which is a more acceptable treatment mode for many patients. Second, neoadjuvant targeted therapy has a higher response rate than neoadjuvant chemotherapy. Therefore, in terms of efficacy, it is also more inclined to target drugs. However, there are still many problems that need to be further explored in the future of neoadjuvant targeted therapy, including the appropriate length of neoadjuvant targeted therapy, whether combination chemotherapy is more effective, and how to identify patients who are primaryly resistant.
The Phase III NeoADAURA study is currently underway, comparing osimtinib monotherapy or combination chemotherapy with standard chemotherapy alone for neoadjuvant therapy EGFR mutation NSCLC. It is believed that with the release of the results of the study, some of these questions will be answered, thus bringing better treatment strategies to patients. As surgeons, we hope to be able to achieve the best surgical resection outcome by optimizing perioperative treatment strategies and bring better postoperative survival benefits to patients. ”
Professor Yang Yue of Peking University Cancer Hospital said: "In the NEOS study, the neoadjuvant therapy of osimtinib has shown satisfactory efficacy and safety, and about half of the patients have tumors in the descending phase, suggesting that the neoadjuvant therapy of ositinib is expected to become a new standard treatment regimen for stage II-IIIB EGFR mutations that can resect lung adenocarcinoma."
For a long time, how to maximize the benefits of patients and prolong survival time has been the research direction of perioperative treatment of lung cancer. The ADAURA study confirmed the benefits of DFS in adjuvant therapy with osimtinib and has become an accepted standard of care regimen. Therefore, in the future, patients with resectable early-stage lung cancer with EGFR mutations may try the perioperative full-course treatment model, that is, preoperative osiminib neoadjuvant therapy in neos studies and postoperative osimertinib adjuvant therapy in the NEOS study, in order to maximize the benefit of patients. ”
Expert resumes
Professor Yang Yue
Chief Physician Doctoral Supervisor Enjoys the special government allowance of the State Council
Director of the Chest Cancer Center of Peking University Cancer Hospital
Deputy Director of The Department of Major Surgery and Director of the Second Department of Thoracic Surgery
Deputy Director of the Department of Thoracic Surgery, Peking University
He is the vice chairman of the Thoracic Surgery Society of Beijing Medical Association and the deputy leader of the Lung Cancer Group
He is a member of the Thoracic and Cardiovascular Surgery Society of the Chinese Medical Association and the deputy leader of the Lung Cancer Group
Vice Chairman of Thoracic Surgery Branch of China Association for the Promotion of International Exchanges in Healthcare
He is a director of the China Tobacco Control Association and a vice chairman of the Tobacco Control and Lung Cancer Prevention and Control Committee
Professor Lu Chao
Peking University Cancer Hospital
Doctor of Oncology Surgery, Deputy Chief Physician
Member of the Lung Cancer Group of the Thoracic Surgery Society of beijing Medical Association
He is a young member of the Thoracic Surgery Committee of the Chinese Association for the Promotion of Medicine
He is a young member of the Thoracic Surgery Committee of the Cross-Strait Medical and Health Exchange Association
Postdoctoral Fellow, Keck School of Medicine, University of Southern California
Mainly engaged in the surgical treatment of lung cancer, esophageal cancer and mediastinal tumors, the research direction is mainly non-small cell lung cancer perioperative chemotherapy and targeted therapy and other comprehensive treatment
As the first person to complete the national 12.5 projects, the National Natural Youth Science Foundation and other scientific research projects, the relevant papers were published in Clinical Lung Cancer, World Journal of Surgical Oncology, Oncology Letters, Chinese Medical Journal and other professional journals as the first author.
bibliography:
[1] Osimertinib as neoadjuvant therapy in patients with EGFR mutated resectable stage II-IIIB lung adenocarcinoma (NEOS): Updated results. ELCC 2022,81MO.
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