Editor's note: The research on immunotherapy in recurrent small cell lung cancer is still in the exploratory stage, and combination therapy is an important research direction. The 2022 World Conference on Lung Cancer (WCLC) also reported relevant research progress. "Tumor Outlook" invited Professor Cheng Ying of Jilin Provincial Cancer Hospital to comment on an oral report on immune checkpoint inhibitors combined with chemotherapy.
Efficacy of Nivolumab and Temozolomide in Extensive Stage Small Cell Lung Cancer after Chemo-Immunotherapy: A Phase II trial 2 Trial.
Introduction
Patients with extensive-stage small cell lung cancer (ES-SCLC) have limited treatment options after progression on first-line chemoimmunotherapy (CIT). Temozolomide is active in ES-SCLC and has been shown to have immunomodulatory effects in patients with advanced cancer, but there are no data in patients after CIT. The final analysis results of nivolumab and temozolomide as second or third line treatment for ES-SCLC patients after CIT progression will be reported at this WCLC meeting.
Methods
NCT03728361 was a nonrandomized, multi-cohort, single-institution, open-label, phase II study (reported separately) evaluating the efficacy of nivolumab plus temozolomide in patients with ES-SCLC and neuroendocrine tumors . ES-SCLC patients who develop disease progression and brain metastasis after CIT treatment are eligible for inclusion. Subjects received nivolumab 480 mg IV and temozolomide 150 mg/m2 for 5 days, with a 28-day treatment cycle. The primary endpoint was best overall response rate (BOR) as assessed by RECIST v1.1. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method. Grading of adverse events using CTCAE v5.
Results
A total of 27 patients were enrolled in the study, of which 11 (41%) were platinum-resistant and 10 (37%) had brain metastases (mCNS, Table 1); 25 patients with progression after CIT were eligible Primary endpoint analysis was performed.
html Among 625 patients with previous CIT treatment, 7 patients experienced remission (28%, 95% CI: 12-49%), and 8 of 27 patients (30%) experienced remission (Figure 1), meeting the predetermined efficacy criteria. mPFS was 2.4 months (95% CI: 1.9-3.4); mOS was 6.3 months (95% CI: 3.7-9.8, Table 1). OS was not related to the number of lines of treatment or mCNS. mOS for patients with mCNS was 9 months (95% CI: 2.0-11.4). Toxicity is similar to CIT treatment toxicity.
Table 1 Patient characteristics and PFS
Figure 1. Waterfall plot of tumor volume change from baseline
Conclusions Nivolumab combined with temozolomide is indicated for the second- and third-line treatment of patients with ES-SCLC who have progressed after first-line CIT and for the treatment of patients with brain metastases. The efficacy shows promise. Professor Cheng Ying commented Small cell lung cancer Although small cell lung cancer is very sensitive to initial treatment, relapse and drug resistance are almost inevitable. Once small cell lung cancer recurs, the treatment effect is poor and the lack of effective treatment methods is a difficult problem that currently plagues clinical practice. The progress of immunotherapy in extensive-stage small cell lung cancer has also promoted its exploration in recurrent small cell lung cancer. Immunotherapy is used for the treatment of recurrent small cell lung cancer. Immunotherapy has improved survival for a variety of solid tumors. It has also been extensively explored in small cell lung cancer. Immunotherapy has been implemented in the first-line treatment of extensive stage small cell lung cancer. A historic and landmark breakthrough, whether it is an internationally developed drug or an immune-targeted drug with China's independent intellectual property rights. PD-L1 inhibitors and PD-1 inhibitor treatment prolong the overall survival of patients. But the treatment of recurrent small cell lung cancer is not always smooth sailing.Although the initial immune single drugs (including nivolumab and pembrolizumab) could achieve durable immune responses in some small cell lung cancer in the phase 1/2 study, they were compared with standard chemotherapy in the subsequent phase 3 study. In comparison, it did not improve OS in recurrent small cell lung cancer. It is suggested that immune single drug has limited efficacy in unselected recurrent small cell lung cancer, and immune combination therapy is a strategy worth exploring in recurrent small cell lung cancer. In 2021, Dwight H. Owen et al. reported the results of a patient with recurrent small cell lung cancer treated with nivolumab combined with temozolomide. After 2 cycles, the tumor target lesions shrank by 82%, and the response lasted for more than 40 weeks. It was also found that the total MDSC in the patient's peripheral blood decreased significantly, and the proliferation of CD4 and CD8+ T cells increased, especially CD8+ T cells. This case report suggests that some patients with relapsed small cell lung cancer can obtain durable responses from treatment with nivolumab plus temozolomide. Nivolumab combined with temozolomide in the treatment of recurrent small cell lung cancer This year’s World Lung Cancer Congress reported a phase 2 study of temozolomide combined with nivolumab in the treatment of recurrent small cell lung cancer. This study allows patients who have failed first-line treatment with immunotherapy combination chemotherapy to be enrolled. The study included 27 patients, and 7 of 25 evaluable patients achieved response, with an ORR of 28%, which is better than the historical data of immunotherapy monotherapy for relapsed small cell lung cancer, and patients can benefit from this combination regardless of whether they have brain metastases or not. benefit from treatment. In research on colon cancer and glioma, it has been reported that temozolomide can induce mismatch repair defects, increase tumor mutation load, and exert a synergistic effect in combination with immune checkpoint drugs. Whether it also plays the same role in small cell lung cancer requires further research. analysis. At the same time, whether patients who benefited from this phase 2 study also have changes in peripheral blood MDSC also needs to be confirmed. The research on immunotherapy in recurrent small cell lung cancer is still in the exploratory stage, and combination therapy is an important research direction. In the future, we should continue to explore markers that can predict the efficacy of combination therapy to promote breakthrough progress in the treatment of recurrent small cell lung cancer. Professor Cheng Ying
Chief Physician Professor Doctoral Supervisor
First-level Professor, Doctoral Supervisor, Postdoctoral Workstation Supervisor
Enjoy Special Allowance from the State Council, Young and Middle-aged Experts with Outstanding Contributions to the Ministry of Health
Secretary of the Party Committee of Jilin Cancer Hospital
Jilin Cancer Center Director
Director of the Malignant Tumor Clinical Research Integrated Diagnosis and Treatment Center of Jilin Provincial Cancer Hospital
Director of Jilin Provincial Lung Cancer Diagnosis and Treatment Center
Vice Chairman of the Chinese Society of Clinical Oncology (CSCO)
Chairman of the CSCO Small Cell Lung Cancer Professional Committee
CSCO Clinical Research Expert Committee Designated Chairman
Deputy Chairman of the Lung Cancer Professional Committee of the Chinese Anti-Cancer Association
Deputy Chairman of the CSCO Non-Small Cell Lung Cancer Professional Committee
Deputy Chairman of the CSCO Oncology Big Data Expert Committee
Deputy Chairman of the Lung Cancer Special Committee of the Oncology Branch of the Chinese Medical Association
Chinese Medical Doctor Association Tumor Deputy Chairman of the Multidisciplinary Diagnosis and Treatment Committee
Deputy Chairman of the Lung Cancer Training Committee of the Chinese Medical Doctor Association
Deputy Chairman of the National Physician Periodic Assessment Oncology Professional Editorial Committee
National Health and Family Planning CommissionMember of the Expert Group on Standardized Diagnosis and Treatment of Common Tumors
Jilin Chairman of the Oncologist Branch of the Provincial Medical Doctors Association
Chairman of the Cancer Professional Committee of the Jilin Provincial Medical Association
Served as an editorial board member of many magazines such as " Chinese Journal of Oncology "
