Prof. Jun Ma: Interpreting the updated key points of the guidelines for nasopharyngeal cancer, looking forward to the progress and prospects of antivascular therapy

*Only for medical professionals to read for reference.
Anti-angiogenic drugs combined with chemotherapy are included in the latest nasopharyngeal cancer guidelines, providing more choices for patients.

The 2021 Chinese Society of Clinical Oncology (CSCO) Guidelines Conference was grandly held on April 23-24.
Experts and scholars from various oncology fields across the country gathered to exchange academic research results, discuss industry development trends, and witness multiple guidelines updates.

The nasopharyngeal cancer guidelines are no exception, and many updates have been made in the field of treatment.

The "medical community" sincerely invites Professor Ma Jun from Sun Yat-sen University Cancer Hospital to interpret the updated points of the guidelines for diagnosis and treatment of nasopharyngeal carcinoma for clinicians and express their professional opinions.

The 2021 CSCO guideline adds anti-vascular + chemotherapy first-line treatment recommendations.
Nasopharyngeal carcinoma is one of the high-incidence tumors in my country, and the main incidence area is concentrated in southern China.

At present, the main treatment for nasopharyngeal carcinoma is comprehensive treatment based on radiotherapy, but a large proportion of patients will have local recurrence or distant metastasis; while the treatment for recurrence or metastasis of nasopharyngeal carcinoma is currently very limited and the prognosis is poor.

2021 Nasopharyngeal Carcinoma Diagnosis and Treatment Guidelines for the first-line treatment of recurrent/metastatic nasopharyngeal carcinoma I recommend new grade I: cisplatin + 5-fluorouracil (5-FU) + local radiotherapy; grade III recommended new: cisplatin + gemcitabine + endurance (Recombinant human endostatin); Second-line and above treatment level I recommendation is newly added: Encourage patients to participate in clinical trials; level III recommendation is new teriprizumab; third-line and above treatment level I is recommended to add teripril Monoclonal antibodies, carrelizumab, encourage patients to participate in clinical trials (Table 1).

Table 1.
2021 Updates on recommendations for the treatment of recurrent/metastatic nasopharyngeal carcinoma, Professor Ma Jun said: “The guidelines for this update mainly focus on two aspects: First, a number of domestically developed immunotherapeutic drugs PD-1 inhibition have been added.
It enriches the options for immunotherapy of recurrent/metastatic nasopharyngeal carcinoma.Second, use recombinant human endostatin combined with chemotherapy as an option for first-line treatment, and bring recommendations for new combination programs for patients with nasopharyngeal cancer.

"Recombinant human endostatin + chemotherapy was included in the first-line treatment recommendation mainly based on the results of a phase II clinical study of recombinant human endostatin combined with cisplatin and gemcitabine in the first-line treatment of metastatic nasopharyngeal carcinoma.

A total of 28 were included in the study .
The results showed that the median progression-free survival (PFS) was 19.
4 months, the 1-year PFS rate was 69.
8%, and the 1-year overall survival (OS) rate reached 90.
2% (Figure 1).
), the objective response rate (ORR) was as high as 85.
7%, and the complete response (CR) rate was as high as 50% [1].

Subsequently, the study expanded the sample to 72 cases, and the updated data showed that the ORR was 77.
8% and the median PFS was 12 Month, the median OS was 19.
5 months (Figure 2) [2].

  Figure 1.
PFS and OS in the case of 28 patients Figure 2.
PFS and OS in the case of patients The median PFS of nasopharyngeal cancer patients receiving gemcitabine + platinum chemotherapy is about 10 months, and the ORR is 42.
7%-73%.
In an indirect comparison, recombinant human endostatin + chemotherapy can increase PFS and ORR; In addition, chemotherapy + anti-vascular therapy is safe and can improve the quality of life.
For example, the phase II study of chemotherapy combined with recombinant human endostatin in the treatment of recurrent and metastatic nasopharyngeal carcinoma showed that patients are well tolerated and the adverse reactions are mainly It is nausea and vomiting associated with chemotherapy.

Recombinant human endostatin combined with chemotherapy has brought new treatment options for patients with nasopharyngeal carcinoma.

"Anti-vascular joint immunotherapy has unlimited potential.
In recent years, immunotherapy represented by anti-PD-1 inhibitors has become a hot spot in the field of tumor research.
A number of clinical studies such as the KEYNOTE-028 study and the NCI-9742 study have shown immunotherapy.
It has a good curative effect in nasopharyngeal carcinoma and successfully knocked on the door of the era of immunotherapy for advanced nasopharyngeal carcinoma in China.

Therefore, this guide has added a number of domestically developed PD-1 inhibitors.

However, it should be noted that immunotherapy still has certain limitations, and more clinical treatment options are needed to further improve the prognosis of patients.

 In order to further improve the efficacy of immunotherapy, researchers began to explore different combined treatment options.

Because anti-angiogenic drugs can enhance certain links in the tumor immune cycle, they have a synergistic anti-tumor effect when used in combination with immunotherapy [3], which has become one of the current exploration and research directions.

Basic research shows that compared with PD-1 inhibitor alone, recombinant human endostatin combined with PD-1 inhibitor can significantly inhibit tumor growth rate, reduce tumor volume, reduce tumor mass and significantly inhibit tumor angiogenesis compared with PD-1 inhibitor alone.

At present, recombinant human endostatin combined with immunotherapeutic drugs PD-1/PD-L1 inhibitors has obtained considerable clinical research results in other cancers.

For example, in the field of lung cancer, Enpower research shows that recombinant human endostatin + standard platinum-containing dual-drug chemotherapy (pemetrexed + carboplatin/cisplatin) + PD-1 inhibitor Sintilizumab, the first-line therapy driver gene The ORR of patients with negative advanced non-squamous non-small cell lung cancer (NSCLC) was 72%, and the ORR of the control group (recombinant human endostatin monotherapy) was 66%.

 Immunotherapy combined with anti-angiogenesis therapy is one of the current research directions for recurrent and metastatic nasopharyngeal carcinoma, and it is also a treatment with great potential.
It is believed that it can bring more benefits to patients in the future.

Looking forward to the future, exploring new treatment options and benefiting groups has continued to progress in recent years, and new treatments have emerged in the field of nasopharyngeal carcinoma.
Are there more effective and safe solutions for recurrent and metastatic nasopharyngeal carcinoma? Become clinicians Questions to think about.

 Professor Ma Jun said: “The combination of multiple treatment methods is one of the important exploration directions, including the combination of systemic drugs, such as immunity + chemotherapy, anti-angiogenesis + chemotherapy, immunity + chemotherapy + vascular targeted drugs, etc.
; As well as the combination of local + systemic treatment methods, such as radiotherapy + immunity, radiotherapy + vascular targeted drugs, etc.
, the current small sample research confirms that the CR rate of recombinant human endostatin + radiotherapy for locally advanced recurrent nasopharyngeal carcinoma can reach 90.
9 %, it is also possible to reduce the occurrence of nasopharyngeal mucosal necrosis after radiotherapy [4]. In addition, new treatment methods are also a major direction of exploration, such as translational therapy research, targeted therapy, new immune checkpoint inhibitors (ICI), other immunotherapies (CAR-T, biological therapy), etc.

 In addition to the optimization of the treatment plan, the screening of the benefited population is also an important direction for future exploration.

How to accurately screen the beneficiaries through biomarkers and give individualized treatment to achieve the most ideal curative effect is an urgent problem to be solved.

"Professor Ma Jun, Executive Deputy Director, Executive Vice President, Chief Physician of Sun Yat-Sen University Cancer Hospital, Chairman of CSCO Nasopharyngeal Cancer Expert Committee, Chinese Anti-Cancer Association Nasopharyngeal Cancer Professional Committee, Special Medical Discipline Commentary by the State Council Academic Degree Committee Deputy convener of the group, member of the Standing Committee of the Chinese Society of Radiation Oncology, Chinese Society of Radiation Oncology, Chairman of the Guangdong Branch of the Chinese Society of Radiation Oncology, Reference [1] Jin T, Li B, Chen XZ.
A phase II trial of endostar combined with gemcitabine and cisplatin chemotherapy in patients with metastatic nasopharyngeal carcinoma(Nct01612286)[J].
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Endostar combined with gemcitabine and cisplatin chemotherapy for patients with metastatic nasopharyngeal carcinoma: an update[J].
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The efficacy and safety of Endostar combined with chemoradiotherapy for patients with advanced, locally recurrent nasopharyngeal carcinoma[J] .
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