Professor Liu Hongxu: Osimertinib adjuvant therapy brings good news to more patients after early NSCLC surgery

*Only for medical professionals to read and refer to the new indications of Osimertinib adjuvant therapy approved, bringing full benefit to patients with early and late NSCLC.

Surgery is still the first choice for the treatment of early stage lung cancer.
Minimally invasive thoracoscopic surgery has the advantages of less bleeding and less trauma and is favored by surgeons.
However, postoperative recurrence and metastasis are still challenges that doctors and patients face.

The comprehensive model of surgical resection combined with postoperative adjuvant targeted therapy has gradually attracted attention.

At present, osimertinib has obtained indications for adjuvant therapy for early stage non-small cell lung cancer (NSCLC) patients in China based on the research results of ADAURA.

In view of this, the "medical community" specially invited Professor Liu Hongxu from Liaoning Cancer Hospital (China Medical University Cancer Hospital) to express his views on related topics.

New surgical techniques for lung cancer emerge with significant advantages.
In recent years, with the emergence of video-assisted thoracoscopy and the rapid development of imaging and imaging technologies, minimally invasive thoracic surgery has entered a rapid development path, and thoracoscopic minimally invasive surgery has increasingly become a thoracic surgery.
The most widely used surgical method in surgery.

Professor Liu Hongxu pointed out: “Currently the new surgical techniques in the field of lung cancer are mainly focused on minimally invasive surgery.
For patients with early stage NSCLC, single-port thoracoscopic surgery can be performed.
The scope of lung resection includes lobectomy, segmental resection, combined segmental resection, and sub-segmental resection.
Lung segment resection, etc.
The use of
thoracoscopy for surgical resection of early NSCLC has been widely accepted, and with the accumulation of experience, the indications of thoracoscopy have expanded to patients with locally advanced NSCLC.
For patients with locally advanced NSCLC
, it can also be used Including thoracoscopic surgery, robot-assisted lung resection.

In addition, for patients with central type lung cancer or locally advanced lung cancer, sleeve lobectomy will be used clinically as much as possible.
This type of operation refers to the removal of the diseased lobe and the connected pulmonary artery or bronchus together, and then reconnect it to the patient.
Preserving the blood vessels or bronchi of the lung lobes can preserve the lung function and lung tissue of the patient to the greatest extent, and reduce the risk of pneumonectomy.
Therefore, the patient is well tolerated, which can significantly improve the postoperative quality of life and prolong the postoperative survival time.

"In short, the advancement of minimally invasive techniques in lung surgery has reduced the morbidity associated with anatomical lung resection and expanded the indications for thoracoscopic resection.

With the improvement of these techniques, patients with higher-stage lung cancer can also safely receive the thoracic cavity.
the mirror cut
Professor Liu Hongxu also stressed: "At present, minimally invasive surgical attention by getting higher and higher, than the traditional open heart surgery, which is less blood loss, less trauma, faster postoperative recovery, fewer complications, for The impact of cardiopulmonary function is small.

For example, in the minimally invasive lung surgery performed by our unit, more than 90% of patients can get out of bed 1 day after surgery, and can be discharged 3-5 days after surgery, even for patients with locally advanced stages or who have undergone sleeve lobectomy.
Being able to be discharged from the hospital within a week will not have a great impact on the patients' normal life and work, and will not cause them a greater psychological burden.

It can be said that, on the basis of pursuing radical resection, minimally invasive surgery pays more attention to the functional protection of patients, which is also a great advantage compared with traditional surgery.

"Targeted drugs have become the preferred auxiliary after resection of early lung cancer.
Surgical resection is the best treatment for patients with NSCLC that can be completely resected.
About 20%-25% of NSCLC patients can receive surgical operations for the purpose of radical resection.
There are still 30%-70% of patients will have recurrence and metastasis, and the prognosis of NSCLC patients is poor, so it is still a huge clinical difficulty to improve the survival and benefit of patients [1-3].

In terms of adjuvant radical postoperative treatment, After decades of basic and clinical research and exploration, the current cisplatin-based adjuvant chemotherapy is the standard treatment after complete resection of stage Ⅱ-ⅢA NSCLC, but the effective rate is low and the adverse reactions are often difficult to tolerate.

How to further improve the radical treatment The survival rate of patients after sexual resection is the common pursuit of all lung cancer-related researchers, including thoracic surgeons.

With the in-depth discussion of molecular biology and the clinical application of molecular targeted drugs, the survival of patients with advanced lung cancer has been improved to a higher level.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is currently the first-line treatment option for advanced NSCLC patients with EGFR-sensitive mutations.
So, can it be further extended to postoperative adjuvant therapy to make radical postoperative EGFR sensitive? Patients with mutations also benefit from it? At present, relevant research results have given answers and are receiving widespread attention.
Adjuvant EGFR-TKI therapy after lung cancer surgery can inhibit the proliferation or metastasis of tumor cells, further improve the efficacy and improve the quality of life of patients.

Professor Liu Hongxu emphasized: “Small-molecule targeted drugs not only have good curative effect, few adverse reactions, but also are convenient to take orally, and patients have high compliance.

If the surgical resection of tumor tissue is based on further use of small molecule drugs as adjuvant therapy, it can be more effective.
Ideal treatment effect.
Therefore, small molecule targeted drugs can also become a very good treatment option for patients with early lung cancer.

"In general, local recurrence or distant metastasis is the main reason for the failure of postoperative treatment of lung cancer.
Selection, especially for NSCLC patients with EGFR-sensitive mutations, the combination of surgical resection and postoperative adjuvant EGFR-TKI will become a very potential treatment model.

Osimertinib escorts the discovery of EGFR sensitive mutations and the verification of the efficacy and safety of EGFR-TKI for the entire treatment of early and advanced NSCLC patients, marking the arrival of the era of precision targeted therapy for NSCLC.

The third-generation EGFR-TKI osimertinib has significant activity against locally advanced or metastatic NSCLC patients with positive EGFR T790M gene mutations, especially for patients with brain metastases or central nervous system metastases, which can further prolong patients And improve the quality of life of patients.

Because of its breakthrough curative effect, in 2015 and early 2016, the United States and Europe successively approved osimertinib for the treatment of EGFR T790M mutation-positive NSCLC patients who have progressed after receiving EGFR-TKI treatment, and formally in March 2017 Approved for listing in China [4].

Osimertinib not only has excellent performance for advanced NSCLC, but also achieved amazing results in the field of early NSCLC treatment.

The disclosure of the results of the ADAURA study [5] means that it is possible to use osimertinib for the adjuvant treatment of early NSCLC after surgery.

This study is a randomized, double-blind phase III study, which aims to evaluate the efficacy and safety of osimertinib for stage ⅠB-ⅢB (T3N2, AJCC8) EGFR mutation-positive patients undergoing adjuvant treatment for NSCLC patients undergoing complete resection (Adjuvant chemotherapy or no adjuvant chemotherapy after surgery).

The results show that osimertinib can bring significant disease-free survival (DFS) benefits to these patients, and the adverse reactions are tolerable.

Based on the results of this research, on November 25, 2020, the National Comprehensive Cancer Network (NCCN) issued "NCCN Clinical Practice Guidelines: NSCLC (2021.
V1)" for the first time recommending osimertinib for stage IB-ⅢB ( T3N2, AJCC8) Adjuvant treatment of NSCLC patients with EGFR mutations after surgery.

At the same time, it is recommended that postoperative surgical tissue/biopsy samples of patients with stage IB-ⅢB (T3N2, AJCC8) NSCLC should be tested for EGFR gene [6].

On December 19 of the same year, the U.
S.
Food and Drug Administration (FDA) formally approved osimertinib for the adjuvant treatment of NSCLC patients with EGFR exon 19 deletion or exon 21 L858R mutation [7].

And this year the indication has been approved for listing in China, bringing good news to more Chinese patients with early-stage NSCLC.

 Expert Profile: Professor Liu Hongxu, Doctor of Medicine, Chief Physician, Professor, Doctoral Supervisor, Vice President of Liaoning Cancer Hospital, Director of Thoracic Surgery, Director of the Chinese Anti-Cancer Association Council Member, International Association for Lung Cancer Research, Staging and Prognosis Committee Member, Liaoning Anti-Cancer Association Lung Cancer Professional Committee Chairman, Liaoning Medical Association Thoracic Surgery Branch, Designated Chairman, Chinese Anti-Cancer Association, Lung Cancer Professional Committee, Chinese Anti-Cancer Association, Mediastinal Tumor Professional Committee, Chinese Medical Doctor Association, Thoracic Surgeons, First Liaoning Young Doctors, Liaoning Province "Xing Liao Talents Plan" "Billions of Engineering Leading Talents Shenyang High-level Leading Talents References: [1] Rami-Porta R, Bolejack V, Crowley J, et al.
The IASLC lung cancer staging project: proposals for the revisions of the T descriptors in the forthcoming eighth edition of the TNM classification for lung cancer.
J Thorac Oncol,2015,10(7): 990-1003.
[2]Takenaka T, Takenoyama M, Yamaguchi M, et al.
Impact of the epidermal growth factor receptor mutation status on the post-recurrence survival of patients with surgically resected non-small-cell lung cancer.
Eur J Cardiothorac Surg,2015, 47 (3): 550－555.
[3]American Cancer Society.
Non-small-cell lung cancer survival rates, by stage［EB /OL］.
［2017-04-05］.
https: / /www.
cancer.