In China, the annual number of patients suffering from lung cancer is up to 784,000 and the incidence and mortality rate of lung cancer account for 20.03% and 26.99% of all malignant tumors respectively, causing lung cancer to be No. 1 among malignant tumors. This makes the scientific research achievements in the treatment of lung cancer attract public attention.
Yilong Wu, Tenured Director of Guangdong Provincial People’s Hospital and Guangdong Lung Cancer Institute, has worked on a study with the teams of 284 global and domestic centers for up to five years, and found that as for the patients suffering from early- and middle-stage lung cancer and with driver gene mutation from stage IB to stage IIIA, if adjuvant therapy with the third-generation targeted drugs is provided for them after early surgical resection, their tumor recurrence risk will decline by 83%.
In the early morning of September 20, Beijing time, the latest top medical journal, The New England Journal of Medicine, published this research finding, which demonstrated the innovation and leadership of Guangdong and China in the international lung cancer treatment field.
This was the first large study on the use of the third-generation EGFR targeted drugs for adjuvant therapy, with 682 enrolled patients from 284 centers across the world’s five continents, making it really an international research and the results more universal.
It is worth mentioning that Chinese researchers have played a core role in the study. Researchers from more than 30 hospitals and over 150 patients have participated in it. The first author of the paper is Professor Yilong Wu, a big shot in the lung cancer field, while famous Academician Jie He and Professor Shun Lu are also important authors.
"This is a high level outcome produced by discovering clinical difficulties from a large number of clinical cases and tremendous work, then condensing them into scientific issues and finally studying them by using a rigorous design scheme," said President Xueqing Yu at the press conference. He further pointed out that such study strategy has brought truly meaningful changes to clinical practice and benefits to patients. He said that big rewards will be given to the research and medical teams of Guangdong Provincial People’s Hospital that have made breakthroughs in major academic fields.
According to different typing of lung cancer, 85% of the lung cancer patients in China are non-small-cell lung cancer (NSCLC) patients, and the patients with the probability of positive EGFR mutation and ALK fusion or rearrangement account for about 50%. Another statistics shows that among the lung cancer patients in China, 1/3 of them are those who suffer from early- and middle-stage lung cancer between stage IB and stage IIIA.
Operation is the main treatment method for early- and middle-stage lung cancer and about 1/3 patients are eligible for operation at the time of diagnosis. "Except for stage 1A ground-glass lung adenocarcinoma that can be completely cured through surgery, with 100% 5-year survival rate, other solid invasive lung cancers have low cure rate and high recurrence rate, and are easy to develop into advanced lung cancer," said Professor Wenzhao Zhong, Pneumosurgery Expert of Guangdong Provincial People's Hospital and Deputy Director of Guangdong Lung Cancer Institute. He further pointed out that in order to solve the problem of the recurrence of lung cancer, relevant clinical studies have been carried out for nearly 30 years.
“Except for patients with stage IA NSCLC, the cure rate of the patients at stage IB-III is not optimistic. The 5-year recurrence rate at stages IB/II/IIIA is 45%, 62% and 76% respectively,” said Professor Wenzhao Zhong. How to solve high recurrence of patients with early- and middle-stage lung cancer is a key part of lung cancer treatment.
The Lung Cancer Institute of Guangdong Provincial People’s Hospital, led by Yilong Wu, has also been exploring how to address the problem of high recurrence rate of patients with early- and middle-stage lung cancer and initiated the Chinese ADAURA study since 2015.
The study is a randomized controlled Phase Ⅲ clinical study, which has explored the benefits brought for the NSCLC patients with EGFR mutation at stagesⅠB-ⅢA who have accepted complete tumor resection by using the third-generation EGFR-TKI targeted drugs as adjuvant treatment. This has brought a disruptive effect. The biggest highlight of the research finding published in the NEJM is that great clinical benefits brought for patients with early- and middle-stage lung cancer by the third-generation postoperative targeted adjuvant treatment selected based on the precise molecular typing of the resected tumor specimens have been observed, with the postoperative recurrence risk decreased by 83%.
Just based on this, Yilong Wu introduced that the clinical data originally planned to be released in 2022 was released in advance for ethical considerations, in order to let the whole world know this clinical data as soon as possible and bring more hope of survival for lung cancer patients.
“In the past, adjuvant therapy studies on other drugs showed that the recurrence rate decreased by 30%. It would be surprising to have 40% or even 60% reduction in disease recurrence rate, but actually our study showed 83% decline, which was really amazing and incredible". In other words, this means that for patients using the third-generation EGFR-TKI targeted drugs as adjuvant therapy, their recurrence rate will decline by 83%, so the risk of disease recurrence is postponed.
"This research finding provides an opportunity for patients with early- and middle-stage lung cancer to be cured (survival time of more than 5 years), and even influences or changes the clinical strategy of doctors for the treatment of these patients. In addition, it provides a great opportunity to change the domestic and foreign guidelines concerning the guiding suggestions on the postoperative treatment of lung cancer patients," said Professor Yilong Wu.
It is noteworthy that this targeted drug is not suitable for all lung cancer patients, but only the specific patients with driver gene mutation selected based on tumor biological characteristics and molecular typing.
In the academic world, the New England Journal of Medicine, Lancet, Journal of the American Medical Association, and the British Medical Journal are collectively known as the "Top Four Medical Journals". This time, the fact that Professor Yilong Wu published the breakthrough finding in lung cancer in the international top clinical journal as the first author showed the leading power of Chinese clinical experts in this field and represented the top academic level of Guangdong Provincial People’s Hospital and Guangdong Lung Cancer Institute.
Professor Yilong Wu said that precise treatment can help improve the overall 5-year survival rate of lung cancer patients in China, and help achieve the "Healthy China 2030" goal. He further said that targeted therapy has brought lung cancer into the era of precision treatment which is a milestone in lung cancer treatment in recent years. With the improvement of precise treatment means such as targeted therapy and immunization therapy, the opportune moment for lung cancer diagnosis and treatment has been constantly moved earlier. These measures can bring greater survival benefits to patients.
Professor Yilong Wu said that after the first-generation EGFR-TKI kicked off precise treatment for lung cancer, targeted drugs such as EGFR and ALK have been updated and developed from the first-generation to the third-generation. When exploring better treatment options, value-based medical treatment has become an important clinical choice orientation. The results of another study proved that the first-line use of the third-generation EGFR-TKI targeted drugs can significantly prolong the disease-free survival and overall survival of patients with EGFR mutation–positive NSCLC advanced disease, with median overall survival of 38.6 months over 3 years. All these efforts are made to improve the 5-year survival rate of lung cancer patients.
With the release of ADAURA research progress, the indications of the third-generation targeted drugs for postoperative adjuvant therapy of early- and middle-stage lung cancer with specific driver gene mutation are expected to be approved by the FDAs of the countries including China as well as European and American countries.
In addition to the changes in the overall treatment plan, the third-generation targeted drugs have also made an important contribution to the disruptive effect achieved this time on the treatment of early- and middle-stage lung cancer.
For advanced lung cancer, the overall survival after the use of the third-generation and first-generation drugs is 38 months and 30 months respectively, obviously the third-generation drugs are better than the first-generation drugs. As for tumor evolution, indeed if the first-generation drugs are used first and take effect, the selective pressure will push tumor to evolve constantly, thus reducing the efficacy of the third-generation drugs.
However, a real problem of the third-generation drugs is that they have not yet been covered by the national basic medical insurance programs and about RMB 15,000 drug cost shall be borne by patients themselves each month. “As for whether to choose the first-generation drugs or the third-generation drugs, we will make a treatment plan according to the actual situation of the patient. Sometimes, a medical problem is not just a medical problem, it is interfered by social, humanistic and many other external factors," said Yilong Wu. As a lung cancer research expert, he will work with his colleagues to strive to make the third-generation drugs affordable for more patients. In addition, the third-generation drugs have currently been approved for the use in the first-line treatment, but there are still no approved indications for which the third-generation drugs can be used for their adjuvant therapy.
If the third-generation drugs are used at the very beginning, then will it be the case that no drugs are available for subsequent treatment after drug resistance?
"From my perspective, in these few years, the first-generation and the third-generation drugs will coexist for the postoperative targeted therapy of early- and middle-stage lung cancer," said Yilong Wu. Product update and replacement does not simply mean that the second generation is used when the first generation is not effective at all, and the third generation is used when the second one fails. There are different focuses in clinical applications.Yilong Wu said that, for example, it is not suggested that patients at stage IA take the third-generation drugs, because their postoperative 5-year survival rate exceeds 80% and the recurrence risk is low and within the current clinically acceptable range. In addition, the drugs themselves can cause rash and other toxic effects, and drug abuse does more harm than good.
”Meanwhile, relevant research and development on the fourth-generation targeted drugs has also been started in the whole lung cancer research field. We should be confident that the number of methods to deal with lung cancer will be increasing, rather than decreasing.”
