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Both OS and PFS have been significantly benefited, making toripalimab + chemotherapy recommended by guidelines!
At present, immunotherapy, i.e., PD-1/L1 inhibitors combined with platinum-doublet chemotherapy, has been the preferred first-line treatment in the systemic drug treatment of patients with extensive-stage small cell lung cancer (SCLC), and a variety of immunotherapy drugs have been approved for indications and put into use in China. However, in the era of evidence-based medicine, the basis for choosing treatment regimens should still return to the efficacy and safety performance in key clinical studies, with the core goal of improving patient prognosis and quality of life, and following scientific principles to make decisions.
On April 26-27, 2024, the CSCO Guidelines Conference jointly sponsored by the Chinese Society of Clinical Oncology (CSCO) and Beijing Heathosco Clinical Oncology Research Foundation was held in JinanThe combination of chemotherapy (etoposide + platinum) has successfully ranked among the recommended regimens, and ES-SCLC patients will welcome a new treatment option!
THIS GUIDELINE RECOMMENDATION IS BASED ON A PHASE III STUDY CALLED EXTENTORCH. The results of this study showed that the first-line treatment of toripalimab + chemotherapy could significantly prolong the progression-free survival (PFS) and overall survival (OS) of patients with extensive-stage SCLC at the same time, becoming the first PD-1 inhibitor to achieve positive results for the dual primary endpoints of PFS and OS in a similar clinical study, and obtained the CSCO "double guideline" for toripalimab + chemotherapy regimen, that is, SCLC diagnosis and treatment guideline level III recommendation (category 1A evidence), The Immune Checkpoint Inhibitors (ICIs) use guideline level II recommendation (category 1A evidence) provides strong evidence. In this regard, the "medical community" specially invited Professor Yu Yan from the Affiliated Cancer Hospital of Harbin Medical University to share his views on the content update.
OS与PFS"两手抓",EXTENTORCH研究多项疗效数据均创最佳
The EXTENTORCH study, which explores toripalimab + chemotherapy for the treatment of extensive-phase SCLC (ES-SCLC), is a randomized, double-blind, placebo-controlled, multicenter Phase III study of 442 patients with histologically or cytologically confirmed ES-SCLC who have not received prior systemic anticancer therapy, have an ECOG PS performance status score of 0-1, and have ≥ 1 measurable tumor lesion according to RECIST v1.1 criteria.
Enrolled patients were randomized 1:1 into toripalimab (n=223) or placebo (n=219) groups, combined with etoposide and platinum-based regimens for 4-6 cycles of induction therapy, after which patients continued to receive toripalimab or placebo maintenance therapy until disease progression or intolerable adverse reactions, and the primary endpoints of the study were investigator-assessed PFS and OS (according to RECIST v 1.1 criteria), secondary endpoints are PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), time to response (TTR), safety, etc., as assessed by a blinded independent review committee (BICR).
Figure 1. EXTENTORCH STUDY DESIGN
IT IS WORTH NOTING THAT IN THE PIVOTAL CLINICAL STUDY OF ES-SCLC IMMUNOTHERAPY, THE EXTENTORCH STUDY IS THE FIRST TO USE PD-1 INHIBITORS AS THE "PROTAGONIST" , and predefined PFS and OS as both primary endpoints (previously only the CASPIAN study with PD-L1 inhibitors had the same preset), which means that it is more difficult for each of the two endpoints to achieve a positive result than the single endpoint (the initial allocation of α is smaller) and statistically demanding, thus evaluating toripalimab + with high standards and stringent requirementsWhether chemotherapy regimens can bring long-term tumor remission and survival benefits to ES-SCLC patients.
THE FINAL RESULTS OF THE PFS AND OS ANALYSES FROM THE EXTENTORCH STUDY WERE OFFICIALLY PRESENTED AT THE 2023 EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY (ESMO) CONGRESS [1]: THE MEDIAN FOLLOW-UP WAS 11.8 MONTHS AT THE CUT-OFF DATE OF THE FINAL PFS ANALYSIS (FEBRUARY 28, 2022), AND TORIPALIMAB PLUS CHEMOTHERAPY SIGNIFICANTLY PROLONGED THE MEDIAN PFS COMPARED WITH PLACEBO (5.8 MONTHS VS. 5.6 MONTHS, HR=0.667, P=0.0002) and a nearly four-fold increase in one-year PFS (18.1% vs. 4.9%).
Figure 2. FINAL ANALYSIS RESULTS OF THE PFS FROM THE EXTENTORCH STUDY
In the final OS analysis (data as of April 20, 2023, median follow-up was 13.7 months), the median OS of patients in the toripalimab group was 14.6 months, which was significantly longer than that of the placebo group at 13.3 months (HR=0.798, P=0.0327), and the 1-year OS rate of patients reached 63.1%, which was not only higher than that of the placebo group (54.9%), but also higher than that of previous PD-1/ L1 inhibitors are the level of pivotal clinical studies in the first-line treatment of ES-SCLC[2].
It is worth noting that the OS benefit of toripalimab + chemotherapy regimen is still based on the higher proportion of patients in the control group (55.2% vs. 69.4%) of late-line anti-tumor therapy, including a higher proportion of ≥ 3rd line therapy (39.5% vs. 59.4%), and a higher proportion of PD-1/L1 inhibitors (13.9% vs. 25.6%).
In terms of treatment safety, the safety of toripalimab + chemotherapy combination therapy is consistent with previous studies, no new safety signals have been observed, adverse events are manageable and controllable, and safety will also be a major plus for toripalimab + chemotherapy regimen in the whole process of SCLC management.
"Balancing" the benefits and accessibility of treatment,
Helping toripalimab + chemotherapy to benefit more patients
THE EXCELLENT RESULTS OF THE EXTENTORCH STUDY PROVIDE STRONG EVIDENCE FOR THE APPLICATION OF TORIPALIMAB + CHEMOTHERAPY IN THE FIRST-LINE SYSTEMIC TREATMENT OF ES-SCLC, AND ARE ALSO THE MAIN BASIS FOR TORIPALIMAB + CHEMOTHERAPY REGIMEN TO BE RECOMMENDED BY CSCO DOUBLE GUIDELINES. While demonstrating good efficacy and safety, toripalimab also has the high accessibility of domestic innovative anti-tumor drugs, which can make the "China Plan" better benefit a wider group of ES-SCLC patients.
AS WE ALL KNOW, ANTI-CANCER THERAPY IS NOT A "ONE-SHOT DEAL", DRUG TREATMENT REQUIRES A CERTAIN AMOUNT OF CONTINUOUS MEDICATION TIME, TAKING THE EXTENTORCH STUDY AND OTHER ES-SCLC IMMUNOTHERAPY CLINICAL STUDIES AS AN EXAMPLE, PATIENTS NEED TO CONTINUE IMMUNOMAINTENANCE THERAPY UNTIL THE DISEASE PROGRESSES OR IS INTOLERABLE TOXICITY AFTER SEVERAL CYCLES OF IMMUNOTHERAPY + CHEMOTHERAPY COMBINATION THERAPY, SO AS TO ACHIEVE THE GOAL OF PROLONGING SURVIVAL, IT IS NECESSARY TO OPTIMIZE THE COST-EFFECTIVE TREATMENT OF DRUGS, IMPROVE DRUG ACCESSIBILITY TO REDUCE THE ECONOMIC BURDEN OF PATIENT TREATMENT.
At present, the corresponding indication marketing application of toripalimab has been accepted by the National Medical Products Administration (NMPA) and is expected to be successfully approved in the near future, which will greatly improve the accessibility of the first-line immunotherapy + chemotherapy regimen for ES-SCLC, so that more patients can afford the treatment expenses and strive for the chance of long-term survival.
brief summary
Successfully passed the test of "high standards and strict requirements" at the statistical level of the EXTENTORCH study, making toripalimab + chemotherapy regimen the first immunologic + chemotherapy regimen in the first-line treatment of ES-SCLC and significantly prolonging the PFS and OS of patientsChemotherapy regimens are widely used, benefiting the majority of ES-SCLC patients after being approved for marketing, bringing more "hope for life".
Expert Profile
Professor Yu Yan
- Director of the Department of Internal Medicine, Affiliated Cancer Hospital of Harbin Medical University, Doctoral Supervisor
- Director of the Chinese Society of Clinical Oncology (CSCO).
- Executive Director of Heilongjiang Anti-Cancer Association
- Director of Heilongjiang Provincial Medical Development Fund
- Member of the Council of Heilongjiang Provincial Medical Association
- Member of the Standing Committee of the Chemotherapy Professional Committee of the Chinese Anti-Cancer Association, China Clinical
- Member of the Standing Committee of the Cancer Support and Rehabilitation Committee of the Chinese Society of Clinical Oncology
- Member of the Standing Committee of the Tumor Palliative Care Branch of the Chinese Medical Promotion Association
- Member of the Standing Committee of the Lung Oncology Professional Committee of the Chinese Medical Education Association
- Member of the Standing Committee of the Cancer Rehabilitation and Palliative Care Committee of the Chinese Anti-Cancer Association
- He is a member of the Lung Cancer Professional Committee of the Chinese Anti-Cancer Association
- Member of the Standing Committee of the Special Committee on Tumor Heterogeneity and Individualized Therapy of the Chinese Anti-Cancer Association
- Chairman of the Lung Cancer Professional Committee of Heilongjiang Medical Doctor Association
- Chairman of the Cancer Palliative Care Committee of Heilongjiang Medical Association
- Chairman of the Cancer Rehabilitation and Palliative Care Professional Committee of Heilongjiang Anti-Cancer Association
- Chairman-elect of the Tumor Drug Clinical Research Committee of Heilongjiang Anti-Cancer Association
- Member of the editorial board of the Chinese Journal of Metastatic Cancer
- Member of the editorial board of the Chinese Journal of Clinical Oncology and Rehabilitation
Bibliography:
[1] 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.
[2] Gomez-Randulfe I, Leporati R, Gupta B, et al. Recent Advances and Future Strategies in First-Line Treatment of ES-SCLC[J]. European Journal of Cancer, 2024: 113581.
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* This article is only for the purpose of providing scientific information to medical professionals and does not represent the views of this platform