* is for reference only for medical professionals
Immune consolidation treatment after radiotherapy and chemotherapy brings survival benefits to patients with stage III lung cancer.
Non-small cell lung cancer (NSCLC) accounts for more than 80% of the total number of lung cancer patients, and locally advanced NSCLC accounts for about 30% of the total number of NSCLC patients [1]. With the leap of immunology, immunotherapy has brought new treatment options for patients with locally advanced NSCLC. The emergence of immune checkpoint inhibitors has become a major milestone in the treatment of phase III unresectable NSCLC. GEMSTONE-301 study [2] provides new evidence for immune consolidation treatment in patients with stage III-impossible NSCLC. Based on this, suglizumab has been approved in China for the treatment of patients with stage III-impossible NSCLC who have not experienced disease progression after receiving platinum-based synchronous or sequential chemoradiation and chemotherapy.
On July 19, 2022, at the "Immuno Cloud College - 2022 Lung Cancer Immunotherapy MDT Case Seminar" hosted by Pfizer , Professor Yang Fang of Harbin Medical University Affiliated Cancer Hospital shared the immunotherapy process of two phase III NSCLC cases. The "medical community" specially invited Professor Yang Fang to explain his clinical diagnosis and treatment strategies in detail, and Professor Liu Baogang, Affiliated Cancer Hospital of Harbin Medical University, gave wonderful comments.
01 Case of immunoconsolidation treatment for advanced pulmonary squamous cell carcinoma sharing
General information:
patient female, 60 years old, was admitted to the hospital on June 25, 2018. Main complaint: cough html for more than 81 months. Current medical history:
In May 2018, there was no obvious cause of cough, which showed intermittent irritating dry cough, occasional coughing, and white foamy phlegm.
CT examination shows the placeholder of the right middle lobe. Past history: Health, no drug allergy, no surgical trauma history. Personal history: has a history of smoking for 20 years and 20 pills per day, and no drinking history. Family history: Mother suffered from lung cancer, breast cancer . The Eastern United States Oncology Collaborative Group (ECOG) physical strength score: 0 points. Physical examination: Respiration sounds clear in both lungs.
auxiliary examination:
On June 26, 2018, ultrasound examination showed that the right supratoplasty lymph node was swollen, 10*9mm, the corticotomy was unclear, and the blood flow signal can be seen, and fatty liver can be seen. No abnormalities were found next to the liver, gallbladder, pancreas, spleen, and abdominal aorta. On June 27, 2018, CT examination of on the chest and head showed that irregular nodules were seen in the middle lobe of the right lung, about 14*13mm in size, and in the shape of lobes. Swelling lymph nodes were seen in the mediastinal , and no abnormalities were found in the CT scan of the head.
Figure 1. June 27, 2018 CT
On June 28, 2018, bone ECT examination showed that the left shoulder, waist 3-5 vertebrae, left iliac bone, and left knee radioactive and radioactive were unevenly distributed on both sides of the ribs. On June 29, 2018, pathological examination: right-locked hypodifferentiated squamous cell carcinoma.
Clinical diagnosis:
Right lung squamous cell carcinoma (T1bN3M0 Stage IIIB).
Lung Cancer Chemotherapy:
July 16, 2018 and August 7, 2018, docetaxel + carboplatin chemotherapy in the first and second cycles. On August 27, 2018, CT review showed that the lesion of the upper lobe of the right lung decreased, and the lymph node of the right was disappeared, and the efficacy was evaluated as partial remission (PR).
Figure 2. June 27, 2018, CT
August 29, 2018, and September 25, 2018, docetaxel + carboplatin chemotherapy in the third and fourth cycles. On October 11, 2018, CT review showed that the lesion of the upper lobe of the right lung was reduced and the efficacy was evaluated as PR.
Figure 3. August 27 and October 11, 2018 CT
chest radiotherapy for lung cancer:
0 October 16, 2018 to November 27, 2018, chest radiotherapy was performed, with a total dose of 60GY, 200cGY/F, a total of 30 times.
Lung Cancer Immunotherapy:
In November 2018, the patient screened for GEMSTONE-301 clinical study, and the results of gene detection showed that the epidermal growth factor receptor (EGFR) gene and anaplastic lymphoma kinase (ALK) were negative. Starting from December 26, 2018, the patient received maintenance treatment for suglizumab, once every 21 days. The re-examination was performed every 2 months until June 28, 2019, and the efficacy was evaluated as stable condition (SD).
Figure 4. December 24, 2018, February 22, 2019, April 26, 2019, June 28, 2019 CT
August 30, 2019, and October 31, 2019, the efficacy evaluation was still SD.
Figure 5. August 30, 2019, October 31, 2019 CT
On October 31, 2019, the CT review showed that pneumonia appeared.
Figure 6. October 31, 2019 CT
March 9, 2020, CT review showed that the pneumonia showed a reduction. On April 20, 2020, the CT review showed that the pneumonia had basically disappeared.
Figure 7. March 9, 2020, April 20, 2020 CT
May 13, 2020 to February 16, 2022, the efficacy continues to be SD. From December 26, 2018 to January 25, 2022, the patient received a total of 51 cycles of suglizumab treatment.
Figure 8. May 13, 2020 to February 16, 2022 CT
Cervical cancer treatment:
Due to irregular vaginal bleeding for more than a month. On January 6, 2022, the review showed uterine effusion, solid cervical lump, and abundant blood circulation. January 14, 2022, pathological examination: cervical squamous cell carcinoma . Clinical diagnosis of stage IB2 cervical cancer.
Figure 9. Re-examination results on January 6, 2022
For cervical cancer, the patient was subjected to in vitro radiation therapy, pelvic DT: 4500cGy, intraluminal post-assembly treatment 5 times, DT: 30Gy, and simultaneous sensitization treatment 3 times (Nidaplatin 50mg for injection).
Table 1. tumor marker changes
Adverse reactions:
Table 2. thyroid function changes from December 24, 2018 to April 8, 2019
Table 3. thyroid function changes from April 28, 2019 to October 13, 2019
Table 4. thyroid function changes from November 26, 2019 to June 30, 2020
Table 5. thyroid function changes from July 19, 2020 to January 4, 2021
Table 6. thyroid function changes from January 27, 2021 to August 1, 2021
Table 7. thyroid function changes from August 24, 2021 to February 14, 2022
02 Expert commented on
This case of lung squamous cell carcinoma patient received 51 cycles of suglizumab maintenance treatment after 4 docetaxel + carboplatin chemotherapy and chest radiotherapy, and obtained long-term benefits. Professor Liu Baogang conducted in-depth analysis and discussion on the diagnosis and treatment process of this patient.
Stage III unresectable NSCLC patients have urgent problems that need to be solved in the past
When NSCLC is diagnosed, nearly one-third of the patients are locally advanced NSCLC, and the treatment options for patients in this population are very limited. Most patients have lost the best surgical treatment opportunity when they are diagnosed, and their standardized treatment measures are synchronous chemoradiation and chemotherapy [3]. In clinical practice, patients with NSCLC who have good physical strength scores, good lung function and no significant decline in body mass are usually selected to receive synchronous chemoradiotherapy. However, because synchronous chemoradiotherapy increases the probability of adverse reactions such as radiopneumonia and grade 3 or 4 acute esophageal toxicity in patients, many patients cannot tolerate synchronous chemoradiotherapy [4]. After receiving concurrent chemoradiotherapy, most patients still relapse, with a 5-year survival rate of only 15% to 25% [3].
In recent years, people have been committed to exploring methods for consolidation of treatment after radiotherapy and chemotherapy. PACIFIC study [5] proves that immunotherapy as a consolidation treatment can enable patients who have not progressed after synchronous chemoradiotherapy to obtain survival benefits, but whether this efficacy is also applicable to patients who have received sequential chemoradiotherapy in the past remains to be further verified by clinical trials.
Sugarlizumab provides a new consolidation treatment option for phase III NSCLC after synchronous or sequential chemoradiation
GEMSTONE-301 study [2] is a randomized double-blind, placebo-controlled phase III clinical study of sugarlizumab as consolidation treatment in locally advanced/unresectable (phase III) NSCLC patients who did not develop disease progression after synchronous or sequential chemoradiation chemoradiation chemoradiation . Between October 26, 2018 and December 30, 2020, 381 patients (intention-to-treat population) were randomly assigned to receive suglizumab (n=255) or placebo (n=126). At the end date of the interim analysis data (March 8, 2021), the median follow-up time for patients in the suglizumab and placebo-treated groups was 14.3 months and 13.7 months, respectively.
At the interim analysis deadline, 123 (48%) and 74 (59%) patients in the suglizumab and placebo-treated groups showed disease progression or death, respectively.Compared with the control group, the progression-free survival (PFS) of the patients in the Suglizumab-treated group evaluated by the Blind Independent Center Review Committee (BICR) was significantly extended (9.0 months vs 5.8 months; HR=0.64; P=0.0026). The 12-month PFS rate in the suglizumab and placebo groups was 45.4% vs 25.6%. Subgroup analysis results show that in most subgroups, suglizumab can bring significant PFS benefits to patients compared with placebo.
GEMSTONE-301 study cracked the dilemma of patients with sequential radiotherapy and chemotherapy. The research results provided patients who had received sequential radiotherapy and chemotherapy with immunosuppressant as a practical basis for consolidation treatment. The 2022 Chinese Society of Clinical Oncology (CSCO) lung cancer diagnosis and treatment guidelines list suglizumab as a Level III recommendation, and is used for consolidation treatment of inoperable stage IIIA, IIIB, and IIIC NSCLC synchronously or sequential chemoradiation and chemotherapy [6].
Expert profile
Liu Baogang Professor
Department of Respiratory Internal Medicine Affiliated Cancer Hospital
Department of Respiratory Internal Medicine Chief Physician Professor
Doctor of Medicine, Postdoctoral Doctoral Supervisor
Expert profile
Yang Fang Professor
Department of Respiratory Internal Medicine Affiliated Cancer Hospital
Department of Respiratory Internal Medicine Deputy Chief Physician Doctor of Medicine
Chinese Anti-Cancer Association Oncology Clinical Chemotherapy Professional Committee
Chinese Anti-Cancer Association Tumor Respiratory Diseases Branch
Chinese Anti-Cancer Association Supporting Treatment Professional Committee
Chinese Anti-Cancer Association Lung Cancer Committee
Chinese Medical Education Association Lung Cancer Committee
Heilongjiang Provincial Chronic Disease Lung Cancer Professional Committee
Zejiemei Product Manual
Statement: The cases involved in the article are for educational and communication purposes only, and do not involve consultation and intervention diagnosis and treatment. The relevant diagnosis and treatment decisions are made independently by the doctor based on the patient's condition.
Approval code: PP-CEJ-CHN-0536
Validity period: 2024-11-03
References:
[1] Yu Silai, Ni Jianjiao, Zhu Zhengfei. Treatment of locally advanced non-small cell lung cancer in the era of immunotherapy: current situation and prospects [J]. Chinese Journal of Cancer, 2022, 32(06): 487-498.
[2] Qing Zhou, Ming Chen, Ou Jiang, et al. Sugemalimab versus placebo after concurrent or sequential chemical therapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 ;23(2):209-219.
[3] Yan Lanfang, Wu Yun. Current status and prospects of locally advanced non-small cell lung cancer [J]. Cancer progress, 2021, 19(19):1957-1960+1973.
[4] Li Jiakang, Xu Jingyan, Yang Mingyi, Zhou Qing. Suglizumab provides new and effective consolidation treatment options for patients with stage III non-small-cell lung cancer who cannot be resected after synchronous or sequential chemoradiotherapy [J]. Journal of Practical Oncology, 2022, 37(03):215-220.
[5] Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemistryotherapy in stage III non-small-cell lung cancer[J]. N Engl J Med, 2017, 377(20): 1919-1929.
[6] 2022 Chinese Society of Clinical Oncology (CSCO) Lung Cancer Diagnosis and Treatment Guide.
*This article is only used to provide scientific information to medical personnel and does not represent the views of this platform
