*For medical professionals only
Good survival benefit and excellent "cost-effectiveness" are the reasons for choosing toripalimab + chemotherapy in the first-line treatment of ES-SCLC.
According to the 2022 China Malignant Tumor Disease Burden Report [1] released by the National Cancer Center, there are 1,060,600 new cases of lung cancer in mainland China every year, still ranking first in the number of malignant tumors, and about 15% of them are small cell lung cancer (SCLC) with higher malignancy and worse prognosis, and about 70% of SCLC patients are diagnosed with relatively severe extensive disease stage (ES-SCLC). The 5-year survival rate is only about 5%-10%, and at least 100,000 new ES-SCLC patients are added every year, which has become a huge challenge for the diagnosis and treatment of lung cancer in mainland China.
Patients with ES-SCLC in the past can only receive chemotherapy-based drug therapy, and the survival prognosis is poor. However, the combination of immunotherapy and chemotherapy represented by PD-1/L1 inhibitors has successfully broken through the bottleneck of ES-SCLC survival. Recently, there has been a series of good news about domestic immunotherapy drugs, among which the combination of PD-1 inhibitor toripalimab and chemotherapy significantly prolonged the progression-free survival (PFS) and overall survival (OS) of patients in the pivotal phase III clinical study EXTENTORCH, becoming the first PD-1 inhibitor in the world to achieve positive results in the dual primary study endpoints of PFS and OS in the pivotal phase III clinical study of ES-SCLC, and the patient's 1-year OS rate has also reached immunity+A new high of 63.1% for chemotherapy regimens [2]!
With the outstanding performance in the EXTENTORCH study, the indication of toripalimab for the first-line treatment of ES-SCLC has recently been officially approved by the National Medical Products Administration (NMPA) of China, which will provide a new option for the first-line treatment of ES-SCLC in mainland China and bring new hope for improving the prognosis of patients! On this occasion, the "medical community" sincerely invites Professor Hu Yi from the General Hospital of the Chinese People's Liberation Army to deeply interpret the research results of EXTENTORCH, and discuss the important value and application prospects of toripalimab combined with chemotherapy in the first-line treatment of ES-SCLC.
01 Under the stricter requirements, the "double positive" results were obtained, and the toripalimab + chemotherapy regimen was even more extraordinary
THE RESULTS OF THE EXTENTORCH STUDY, IN WHICH TORIPALIMAB + CHEMOTHERAPY WAS APPROVED FOR THE FIRST-LINE TREATMENT OF ES-SCLC, WERE PRESENTED AT THE 2023 EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY (ESMO) ANNUAL MEETING. The study is a typical randomized, double-blind, placebo-controlled, multicenter clinical phase III study, and the study design is shown in Figure 1. NOTABLY, THE EXTENTORCH STUDY SET TWO PRIMARY ENDPOINTS, INVESTIGATOR-ASSESSED PFS AND OS. PFS can more directly evaluate the efficacy of innovative anti-tumor drugs [3], while OS is the "gold standard" of anti-tumor therapy in the traditional sense, with PFS and OS as the primary endpoints, which is also a rare and bold design in the key clinical study of immuno+chemotherapy regimen in ES-SCLC.
Figure 1. EXTENTORCH STUDY DESIGN
FINAL ANALYSIS OF PFS FROM THE EXTENTORCH STUDY [2] SHOWED THAT PATIENTS IN THE TORIPALIMAB COMBINATION GROUP HAD A SIGNIFICANTLY LONGER MEDIAN PFS (HR=0.667, P=0.0002, FIGURE 2) COMPARED WITH THE PLACEBO CONTROL GROUP, ACHIEVING A POSITIVE ENDPOINT AND A NEARLY FOUR-FOLD INCREASE IN THE 1-YEAR PFS RATE (18.1% VS. 4.9%).
Figure 2. FINAL ANALYSIS RESULTS OF THE PFS FROM THE EXTENTORCH STUDY
In the final OS analysis, the median OS of patients in the toripalimab combination group was 14.6 months, which was also significantly longer than 1.3 months in the placebo group (HR=0.798, P=0.0327). Both primary endpoints were positive, and patients in the toripalimab combination group achieved a 1-year OS rate of 63.1 percent, which was higher than all other previous PD-1/L1 inhibitor plus chemotherapy regimens in a pivotal clinical study of the first-line treatment of ES-SCLC (1-year OS rate of 51.7 to 62.9 percent) [2].
IT IS IMPORTANT TO NOTE THAT THE PROPORTION OF PATIENTS IN THE CONTROL GROUP WHO RECEIVED BACK-LINE ANTI-TUMOR THERAPY (55.2% vs. 69.4%) AND THE PROPORTION OF PATIENTS WHO RECEIVED LATE-LINE IMMUNOTHERAPY (I.E., PD-1/L1 INHIBITORS, 13.9% VS. 25.6%) IN THE EXTENTORCH STUDY WERE HIGHER THAN THOSE IN THE COMBINATION THERAPY GROUP WITH TORIPALIMAB, WHICH WOULD HAVE AN IMPACT ON THE STUDY OS DATA. However, even so, toripalimab combined with chemotherapy still achieved a positive OS endpoint result, successfully passed the "gold standard" certification of clinical studies to prolong survival, and the positive PFS endpoint result also confirmed the clear value of toripalimab combined with chemotherapy in delaying the progression of patients and improving clinical symptoms.
In terms of safety, toripalimab combined with chemotherapy was generally well tolerated, and the adverse reactions were mainly mild to moderate and controllable. The rates of treatment-emergent adverse events (TEAEs), grade ≥3 TEAEs, and TEAEs leading to death were similar in both groups. The most common TEAEs are neutrophils and leukopenia. The incidence of immune-related adverse events (irAEs) in the toripalimab plus chemotherapy arm was 28.8 percent and the incidence of grade 3 irAEs ≥ 9.9 percent, with no unexpected safety events[2].
In addition, the EXTENTORCH study also designed exploratory endpoints for efficacy prediction biomarkers, and whole-exome sequencing (WES) was performed on 300 of these patients, which once again confirmed that tumor mutational burden (TMB) could not be used as a predictor of efficacy in immunotherapy combined with chemotherapy. However, it was found that PFS (4.14 months vs. 4.14 months) in patients without mutations who received toripalimab in combination with chemotherapy compared with patients with integrin-mediated genomic alterations in the focal adhesion complex was found to be 4.14 months vers. 6.24 months) and OS (10.81 versus 16.56 months) were more significant, suggesting that patients without integrin-mediated focal adhesion complex genomic mutations are potential beneficiaries of immunotherapy in ES-SCLC [2].
02With good clinical benefits and excellent cost performance, toripalimab is more "friendly" to Chinese patients
Although "immuno+chemotherapy" regimens such as toripalimab combined with chemotherapy significantly prolonged the survival of patients compared with traditional chemotherapy, the net survival benefit was still limited, and the median OS of patients compared with driver-negative advanced non-small cell lung cancer was also different (12-15.8 months vs. 18-27 months). Therefore, in the process of anti-tumor treatment, it is more cost-effective to choose drugs with lower prices to save patients' treatment costs, which is also of great significance for the rational allocation and use of medical and health resources.
As the world's first innovative biologic drug independently developed and manufactured in China approved by the U.S. Food and Drug Administration (FDA), toripalimab has greatly improved the accessibility of the drug while ensuring high quality and its relatively affordable price strategy. Toripalimab is only 2,438 yuan per treatment cycle, which is only 4%-15% of the price of other approved immune drugs for the same indication.
In the case that a variety of immunotherapy drugs have achieved positive results in key clinical studies of ES-SCLC and the level of evidence-based medicine is similar, the lower treatment cost of toripalimab has undoubtedly lowered the "treatment threshold" of ES-SCLC immunoleast+ chemotherapy regimen, so that more patients can win the opportunity to benefit from treatment, and is expected to strive for more vitality.
brief summary
Based on the high-quality evidence-based medical evidence provided by the "double positive" results of the EXTENTORCH study, the indication of toripalimab ES-SCLC with clear evidence of therapeutic benefit was officially approved, adding a new regimen for the first-line treatment of ES-SCLC patients in mainland China, and the toripalimab combined with chemotherapy regimen has good efficacy, safety and cost-effectiveness, which will become an important "plus" in clinical application, making this regimen a popular treatment choice for clinicians and patients.
Expert Profile
Professor Hu Yi
General Hospital of the Chinese People's Liberation Army
Director of the Department of Oncology of the PLA General Hospital
Director of the Key Laboratory of the Ministry of Education of the People's Republic of China, the Key Laboratory of Beijing Municipality, and the Key Laboratory of Oncology of the People's Republic of China
He is the head of the oncology professional group of the clinical trial pharmacology base of the PLA General Hospital
Director of the Department of Respiratory Oncology and Interventional Endoscopy
Chief physician, professor and doctoral supervisor
Consultation expert of the Central Health Care Commission, advanced individual of central health care
Consultation expert of the Health Care Committee of the Central Military Commission
Young and middle-aged experts who have made outstanding contributions to the national "Millions of Talents Project".
Deputy Editor-in-Chief of the PLA Medical Journal
Member of the editorial board of the Chinese Journal of Oncology
Chairman of the Geriatric Cancer Prevention and Treatment Committee of the Chinese Society of Clinical Oncology (CSCO).
Chairman of the Molecular Oncology and Immunotherapy Professional Committee of the Chinese Association of Research Hospitals
Vice Chairman of the Oncology Branch of Beijing Medical Association
Director of the Chinese Society of Clinical Oncology (CSCO).
He is a member of the Standing Committee of the Non-Small Cell Lung Cancer Committee of the Chinese Society of Clinical Oncology (CSCO).
He is a member of the Standing Committee of the Small Cell Lung Cancer Committee of the Chinese Society of Clinical Oncology (CSCO).
He is a member of the Standing Committee of the Sarcoma and Melanoma Committee of the Chinese Society of Clinical Oncology (CSCO).
Member of the Standing Committee of the Respiratory Endoscopy Association of the World Endoscopy Association
He is a member of the Standing Committee of the Multidisciplinary Diagnosis and Treatment Committee of the Chinese Medical Doctor Association
He is a member of the Oncology Branch of the Chinese Medical Association
Evaluation expert of the National Natural Science Foundation of China
Executive Editor-in-Chief of JCO Chinese Lung Cancer Journal
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Bibliography:
[1] Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. Journal of the National Cancer Center, 2024.
[2] Cheng Y, Liu Y, Zhang W, et al. LBA93 EXTENTORCH: A randomized, phase III trial of toripalimab versus placebo, in combination with chemotherapy as a first-line therapy for patients with extensive stage small cell lung cancer (ES-SCLC)[J]. Annals of Oncology, 2023, 34(Supplement 2): S1334.
[3] Patil S, Agarwal V, Drupad H S. Significance of emerging clinical oncology endpoints in support of overall survival[J]. Indian Journal of Cancer, 2022, 59(Suppl 1): S106-S118.
* This article is only for the purpose of providing scientific information to medical professionals and does not represent the views of this platform