The 2022 Chinese Society of Clinical Oncology (CSCO) Guidelines has just come to an end, and at this exciting academic event where big coffee gathers, many experts and scholars in the field of oncology have explained in depth the highlights, main points and difficulties of the guideline update. The clinical use of immune checkpoint inhibitors has always been the focus of clinical attention.
Professor Wang Jun of the Cancer Center of the First Affiliated Hospital of Shandong First Medical University impressed all the experts and scholars attending the meeting with his updated interpretation of the "Guidelines for the Clinical Application of Immune Checkpoint Inhibitors of the Chinese Society of Clinical Oncology (CSCO) 2022".
Professor Wang Jun
The First Affiliated Hospital of Shandong First Medical University
Chief Physician, Ph.D., Doctoral Supervisor
Deputy Director of the Department of Oncology, The First Affiliated Hospital of Shandong First Medical University
Deputy Director of Shandong Lung Cancer Research Institute
Director of the Chinese Society of Clinical Oncology (CSCO).
Vice Chairman and Secretary General of the CSCO Expert Committee on Immunotherapy
Vice Chair of the CSCO Expert Committee on Patient Education
Member of the CSCO Expert Committee on Non-Small Cell Lung Cancer
Author of CSCO Guidelines for the Administration of Toxicity Associated with Immune Checkpoint Inhibitors
Author of CSCO's Guidelines for the Clinical Application of Immune Checkpoint Inhibitors
Visiting Professor, MD Anderson Cancer Center, University of Texas, USA
Communication review expert of the National Natural Science Foundation of China
Associate Editor of Patient Education Manual for Adverse Reactions Related to Tumor Immunotherapy
The current use of immune checkpoint inhibitors (ICI) is expanding rapidly. From 2011 to 2018, the use and efficiency of immune checkpoint inhibitors continued to increase, and according to 2018 data in the United States, nearly 50% of patients with indications for immune checkpoint inhibitors were enrolled. In China, the application range of immune checkpoint inhibitors is also expanding, reaching 20% to 30% in some areas. It is believed that with the continuous development of research work, more and more people will benefit from immune checkpoint inhibitor therapy.
In this year's guideline update, the number of chapters related to the clinical application of immune checkpoint inhibitors has been increased from 17 to 18, and the content of highly microsatellite instability (MSI-H)/mismatch repair defect (dMMR) and tumor mutation burden (TMB-H) solid tumors has been added.
The 18 chapters cover each of the different tumor types, including esophageal cancer, non-small cell lung cancer, breast cancer, advanced hepatocellular carcinoma, advanced kidney cancer, cervical cancer, recurrent ovarian cancer, recurrent/refractory malignant lymphoma, relapsed or metastatic head and neck squamous cell carcinoma, pleural mesothelioma, extensive small cell carcinoma, advanced gastric cancer, advanced colorectal cancer, urothelial carcinoma, recurrent or metastatic endometrial cancer, malignant melanoma, skin cancer (non-malignant melanoma), and the new MSI-H//new MSI-H//MSI dMMR and TMB-H solid tumors. This section involves a total of 11 immune checkpoint inhibitors, covering 41 indications, and strives to provide more comprehensive reference value for clinical work.
This time highlights: recurrent or metastatic head and neck squamous cell carcinoma, esophageal carcinoma, non-small cell carcinoma, extensive small cell carcinoma, pleural mesothelioma, breast cancer, advanced gastric cancer, intermediate and advanced hepatocellular carcinoma.
Recurrent or metastatic head and neck squamous cell carcinoma
Major updates
1. Added "carellizumab or teriplizumab + gemcitabine + cisplatin" as a first-line treatment of nasopharyngeal carcinoma I. recommendation, "tirelizumab + gemcitabine + cisplatin" listed as a level III recommendation.
2. Upgrading "carellizumab" to nasopharyngeal carcinoma second-line or salvage treatment level II. is recommended.
3. Add "paenoprulimab" listed as a second-line or salvage treatment level III recommendation.
Updated interpretation
The median progression-free survival (mPFS) period of the CAPTAIN-1st study assessing carellizumab plus GP (gemcitabine + cisplatin is called the GP regimen) was 10.8 months, which was extended by 6.9 months (P<0.0001) compared with the GP group, reducing the risk of death or disease progression by 49%. The IRC assessed a 1-year progression-free survival (PFS) rate of carellizumab plus GP at 2 times that of GP (45.8% vs. 20.5%) and an 18-month PFS rate of approximately 3 times that of GP (34.8% versus 12.7%). Carrelizumab combined with GP significantly prolongs patient PFS.
The JUPITER-02 study of triprprimumab combined with chemotherapy mPFS was significantly prolonged, from 8.0 months in the placebo group to 11.7 months (P=0.0003).
Esophageal carcinoma
Major updates
1. Add "triprimumab + cisplatin + paclitaxel, sindilisumab + cisplatin + paclitaxel / 5-fluorouracil (5-FU), navulisumab + cisplatin + 5-FU, navulisumab + ipilimumab, cariblizumab + cisplatin + paclitaxel" as the first-line treatment of Grade I recommendation"
2. Second-line treatment added "terelizumab" level I recommendation.
Non-small cell lung cancer (NSCLC) (non-squamous NSCLC without driver gene mutations)
Major updates
1. Upgrade "atenizizumab [programmed death ligand 1 (PD-L1) tumor cells (TC) ≥50% or tumor-infiltrated immune cells (IC) ≥10%] (class 1A), terelizumab combined with pemetrexed and platinum (class 1A)" to stage IV. driverless gene, non-scaly NSCLC first-line treatment level I recommendation.
2. "Atenizumab plus pemetrexed + carboplatin (class 1A), suglimab combined with pemetrexed and platinum (class 1A)" was listed as a stage IV. driverless gene, non-squamous NSCLC first-line treatment first-line treatment recommendation, and "treprilizumab combined with pemetrexed and platinum (class 1A)" was listed as a stage IV. driverless gene, non-scale NSCLC first-line treatment level II recommendation.
3. Upgrading "tirelizumab (class 1A)" to a second-line treatment of advanced non-scaly NSCLC is recommended for level I.
4. "Use of sugliltimab (class 1A) after simultaneous or sequential chemoradiotherapy" as a locally advanced non-squamous NSCLC consolidation therapy level III recommendation.
5. "Maintenance therapy with altelizumab after phase II.A-III.A postoperative adjuvant chemotherapy (PD-L1 TC≥1%)" was listed as a non-squamous NSCLC adjuvant therapy level II. recommendation.
6. "Navulilizumab plus platinum-containing chemotherapy (class 1A)" is listed as a non-squamous NSCLC neoadjuvant therapy level III recommendation.
Updated interpretation
IMpower010 is the first study of early-stage NSCLC postoperative adjuvant therapy, and the disease-free survival (DFS) phase of the early NSCLC postoperative adjuvant therapy group with atenolizumab was significantly better than that of the optimal supportive care (BSC) group.
On October 15, 2021, the U.S. Food and Drug Administration (FDA) approved atenizolizumab for adjuvant therapy after phase II.~III.A PD-L1≥1% of NSCLC after platinum chemotherapy.
CHECKMATE 816 study: I.B-III.A stage NSCLC neoadjuvant chemotherapy combined with immunotherapy. Navuliliumab (NIVO) plus chemotherapy versus chemotherapy neoadjuvant therapy significantly improves pCR (24.0% vs. 2.2%) in patients with resectable NSCLC, while the safety is tolerable.
NSCLC (squamous NSCLC without driver gene mutations)
Major updates
1. Upgrade "atenizumab (limited to PD-L1 TC≥50% or IC≥10%) (class 1A), sindilimab plus gemcitabine and platinum (class 1A), carellidizumab plus paclitaxel and platinum (class 1A)" to the advanced squamous NSCLC first-line treatment level I. recommendation.
2. "Sugli maclizumab combined with paclitaxel and platinum (class 1A)" was listed as a first-line treatment recommendation for advanced squamous NSCLC, and "piambromibab plus paclitaxel and platinum (class 1A), tereprimumab combined with pemetrexed and platinum (class 1A)" was listed as a level II recommendation for the first-line treatment of advanced squamous NSCLC.
3. Upgrading "terelizumab (class 1A)" to a second-line treatment of advanced squamous NSCLC is recommended for level I.
4. "Use of suglimab (class A)" after simultaneous or sequential chemoradiotherapy" is listed as a locally advanced squamous Squamous NSCLC consolidation therapy level III recommendation.
5. "Maintenance therapy of atenizumab after phase II.A~III.A postoperative adjuvant chemotherapy (PD-L1 TC≥1%)" was listed as a squamous NSCLC adjuvant therapy level II. recommended.
6. "Navulilizumab plus platinum-containing chemotherapy (class 1A)" is listed as a squamous NSCLC neoadjuvant therapy level III recommendation.
Extensive stage small cell lung cancer
Major updates
Adjusted "duvalliumab + etoposide/carboplatin or cisplatin" to the first-line treatment of wide-stage small cell lung cancer Level I recommendation
Pleural mesothelioma
Major updates
In first-line therapy, grade I recommends no longer distinguishing between non-epithelial and epithelial malignant pleural mesothelioma (MPM); level II recommends adding "duvalliumab plus pemetrexed + cisplatin"; and level III recommends adding "navuliliumab + combined pemetrexed + cisplatin".
In the second-line treatment, "navuliliumab" was changed from level III recommendation to level I recommendation; level III recommendation increased "pambolizumab"; "third-line and above treatment" was added; "navulilizumab" was recommended by level I. and "pastolizumab" was recommended by level III.
breast cancer
Major updates
Update/add comments only.
Advanced stomach cancer
Major updates
In the first-line treatment, the new "PD-L1 combined positive score (CPS) ≥5, XELOX combined sindilimab (class 1A evidence)" was recommended as a grade I recommendation; New "PD-L1 CPS navuliyumab (class 1B)" and "PD-L1 CPS sindilizumab (class 1B)" level II recommendation.
In the first-line treatment, the addition of "navulijumab plus ipicumab (class 2B, dMMR/MSI-H), perbolizumab monodrug combined with cisplatin/fluorouracil (class 2B, dMMR/MSI-H), navuliyumab combined with FOLFOX/XELOX (class 2B, dMMR/MSI-H)" was added as a grade III recommendation, and the content of "first-line treatment (HER2 positive)" was added.
Second-line therapy, with new envolizumab (class 2A evidence, dMMR/MSI-H) as a grade I recommendation.
Third-line or posterior therapy, remove the "pambolizumab" level II recommendation.
Updated interpretation
The ORIENT-16 study is the first phase III clinical study in China to confirm that first-line immune therapy significantly prolongs the overall survival of advanced gastric cancer. Sinodilliumab + chemotherapy compared with placebo + chemotherapy, PD-L1 CPS≥5 and the whole population, all showed a significant benefit in overall survival; the total survival (OS) period of sinodiliumab + chemotherapy PD-L1 CPS ≥5 was extended by 5.5 months (18.4 months versus 12.9 months, P=0.0023), the risk of death was reduced by 34%, and the intratopic OS in the whole population was extended by 2.9 months (15.2 months versus 12.3 months, P=0.0090), and the risk of death was reduced by 23%.
Keynote-811 is an exploration of immune-combined protocols in human epidermal growth factor receptor-2 (HER2+) metastatic gastric or gastroesophageal-conjugate carcinoma. Compared with placebo + trastuzumab + chemotherapy, the objective response rate (ORR) increased by 22.7% (74.4% versus 51.9%, P=0.00006), the complete response (CR) increased by 8%, and the sustained response time (DOR) was extended by 1.1 months.
Aaaah
Intermediate and advanced hepatocellular carcinoma
Major updates
The first-line strategy of immunotherapy for advanced hepatocellular carcinoma (HCC) was selected, and "sindilizumab plus bevacizumab analogue (class 1A)" was upgraded to a class I recommendation; "duvalliumab plus tiximumab (class 1A evidence)" was listed as a level I recommendation.
The second-line strategy of immunotherapy in the middle and late HCC was selected, and the "navulilizumab" level I recommendation was deleted, and the "tirelizumab" was listed as an I recommendation.
Updated interpretation
The ORIENT-32 study was the first PD-1 combined phase III study to reach a positive endpoint, with sindili monoclonal antibody versus bevacizumab versus sorafenib, median survival not reached, with significant differences in survival benefit compared with sorafenib (mOS, NE versus 10.4 months, PP
brief summary
1
With the extensive development of clinical trials and the accumulation of evidence, many ICI have added new application recommendations, some recommendations have been upgraded, and a small number of recommendations have been removed.
2
ICIs have been approved for clinical trials, and have "competed for hundreds of boats" in the four major tumor species (NSCLC, esophageal cancer, gastric cancer, and liver cancer), but there are also supplements, enriching the multi-line choice of immunotherapy.
3
Immune combination strategies are constantly enriched, such as immune combined immunity (new esophageal cancer, liver cancer), immune combination anti-angiogenesis, etc.
4
Immunotherapy continues to move forward, and early tumor immunotherapy has been recommended, such as NSCLC, neoadjuvant therapy for esophageal cancer.
Disclaimer: WuXi AppTec's content team focuses on the global biomedical health research process. This article is for informational purposes only and the views expressed herein do not represent the position of WuXi AppTec, nor do they represent WuXi AppTec's support for or opposition to the views expressed herein. This article is also not recommended for treatment options. For guidance on treatment options, please visit a regular hospital.
Share, like, watch, pass on new medical knowledge
![Hengrui Pharmaceutical Carellizumab has added two new indications, and the total number of approved indications has reached 8[fig]](data:image/gif;base64,R0lGODlhAQABAIAAAP///wAAACwAAAAAAQABAAACAkQBADs=)