Case Sharing|To live up to the "Tuo", Tuoyi treats nasopharyngeal carcinoma with high risk of recurrence and metastasis up to CR!

Tuoyi® (Treprizumab Injection) has been approved by the National Medical Products Administration (NMPA) for the treatment of recurrent/metastatic nasopharyngeal cancer patients who have previously failed second-line and above systemic treatments, becoming a global The first PD-1 monoclonal antibody approved for nasopharyngeal carcinoma indication.

Today, Professor Chen Qiuyan and Dr.
Wen Dongxiang from the Cancer Center of Sun Yat-Sen University brought us a case introduction of a patient with nasopharyngeal carcinoma at high risk of recurrence and metastasis, and provided reference for clinicians.

Case profile Medical history and auxiliary examinations The patient is a 58-year-old female who was admitted to the hospital on May 11, 2020.

Main complaint: repeated tears and blood for more than 3 months.

History of present illness: The patient had no obvious inducement before 3 months, and the patient had nasal discharge, red color, low volume, no other discomfort, and no attention was paid to it.

The symptoms gradually worsened, and he went to the local hospital for further nasopharyngeal biopsy.
The pathology showed: undifferentiated non-keratinizing carcinoma of the nasopharyngeal carcinoma.

Untreated, he went to the Sun Yat-Sen University Cancer Center for treatment.

Physical examination: nodular masses on the parietal posterior wall of both sides of the nasopharynx; several lymph nodes can be palpable in the Ⅱ~Ⅳ areas of the right side of the neck, the largest one is about 2*2.
5cm, with hard texture, clear borders, good mobility, no tenderness.

Auxiliary examination: electronic nasopharyngoscope: nodular masses on the top, posterior, and right side walls of the nasopharynx.

MRI of the head and neck: thickening of the nasopharyngeal apical wall, apical posterior wall, and right side wall, and a mass in the right pharyngeal recess.

The right tensor velocalis muscle, levator velocalis muscle, and the right long head muscle were invaded.

Bone destruction at the base of the skull.

Swollen lymph nodes were seen in the posterior pharyngeal space on both sides, the largest one was about 25*21mm.

There are multiple lymph nodes in the Ⅱ~Ⅳ areas of the double neck, the largest one is about 23mm*16mm.

Figure 1 Head and neck MRI plain scan + enhanced (baseline) results PET/CT: Nasopharyngeal apical wall, apical posterior wall, and right side wall mucosa is thickened and metabolically active, SUVmax is about 20.
1, in line with nasopharyngeal carcinoma, the lesion invades the skull base bone And right rupture hole; after double pharynx, lymph node metabolism is active, SUVmax is about 15.
9, right neck area Ⅱ~Ⅳ and left neck area Ⅱ swollen lymph node metabolism is active, considering metastasis, SUVmax is about 18.
5, the larger one is about 1.
5*2.
6cm.

No distant transfer.

Figure 2 PET/CT (baseline) results clinical diagnosis of undifferentiated non-keratinizing carcinoma of the nasopharyngeal (T3N3M0, stage Ⅳa, AJCC 8th stage).

The first stage of treatment (neoadjuvant therapy, double-blind): On May 12 and May 26, 2020, two courses of teriprizumab/placebo were given.

First re-examination: On June 8, 2020, nasopharyngeal and neck MRI plain scan + enhanced examination.
Tips: nasopharyngeal lesions, bilateral retropharyngeal space lymph nodes and bilateral cervical lymph nodes are all significantly smaller than before; electronic nasopharyngoscope Tip: There is no obvious mass in the nasopharynx, and the mucosa of the parietal posterior wall is slightly raised.

The results of Epstein-Barr virus (EBV) DNA on May 27, 2020 (after 1 course of Teriplizumab) and June 10 (after 2 courses of Teriplizumab) showed that the DNA results were all 0 copy/ml.

The overall curative effect is partial remission (PR), and the nasopharyngeal curative effect is complete remission (CR).

Table 1 Results of the first review (after 2 courses of neoadjuvant therapy with teriprizumab), the second stage (contemporaneous radiotherapy and chemotherapy [CCRT]): From June 8 to July 23, 2020, give intensity-modulated radiotherapy ( IMRT) + Cisplatin 100mg/m2 (Day 1, 22 and 43).

The third stage (adjuvant therapy, double-blind): From July 27 to December 29, 2020, treprisumab 240mg Q3W was given for 8 courses.

Second re-examination: on October 18, 2020, nasopharyngeal and neck MRI scan + enhanced examination.
Tips: Compared with the MR results on June 10, the nasopharyngeal lesions did not change significantly, and the bilateral posterior pharyngeal space lymph nodes and neck Several lymph nodes on both sides are smaller than before. On October 21, 2020, the electronic nasopharyngoscope showed that there was no obvious mass in the nasopharynx.

The overall effect of the patient is complete remission (CR).

Table 2 Results of the second re-examination (after CCRT, in adjuvant treatment with teriprizumab) Case analysis The patient was diagnosed as "nasopharyngeal undifferentiated non-keratinizing carcinoma" (T3N3M0, stage IVa), with an EBV DNA of 1.
84 x104 copy/mL, it belongs to nasopharyngeal carcinoma with high risk of recurrence and metastasis.

In the first stage, he was given 2 courses of induction therapy with teriprizumab, CCRT was given in the second stage, and 8 courses of adjuvant treatment with teriprizumab were given in the third stage.

After a course of induction therapy with teriprizumab in this patient, the EBV DNA was reduced to 0 copy/ml.

According to the latest POLARIS-02 research results published in JCO magazine, EBV titer changes can be used as an effective biomarker for predicting the efficacy of immune checkpoint inhibitors.
After 1 month of immunotherapy, the EBV titer decreased by ≥50% from the baseline.
Of patients, the objective response rate (ORR) is as high as 48.
3%1.

The patient’s reexamination after 2 courses of teriprizumab induction therapy showed that the nasopharyngeal lesions reached CR, and the retropharyngeal lymph nodes and cervical lymph nodes were also significantly smaller than before.
It was further confirmed that the decline in EBV titer is a predictor of anti-tumor therapy, especially immunity Effective indicator of treatment effect.

During the treatment of this patient, the main adverse reactions that occurred were third-degree myelosuppression, first-degree radiation dermatitis, and first-degree radiation oral mucositis, which were mainly related to chemotherapy and radiotherapy.
There were no immune-related adverse reactions, and the overall safety was controllable.

Expert comments: Professor Chen Qiuyan, Chief Physician, Department of Nasopharyngeal, Sun Yat-sen University Cancer Prevention and Treatment Center, Doctoral Supervisor, Member of the Ethics Committee, Director of the Personnel Division, Sun Yat-sen University Cancer Prevention and Treatment Center, Vice Chairman, Guangdong Provincial Society of Clinical Medicine, Nasopharyngeal Carcinoma Precision Therapy Professional Committee, Guangdong Provincial Society for Precision Medicine Applications Vice Chairman of Head and Neck Cancer Branch, Member of the Nasopharyngeal Carcinoma Professional Committee of the Guangdong Anti-Cancer Association, Member of the Standing Committee of the Cancer Biotherapy Professional Committee of the Cancer Prevention and Management Branch of Guangdong Hospital Association, CCRT is the standard treatment for locally advanced (stage Ⅲ~Ⅳa) nasopharyngeal carcinoma, but After receiving CCRT, about 30% of these patients still have recurrence and metastasis2,3.

Studies have shown that the prognosis of patients with plasma EBV DNA ≥1500 copy/ml before treatment is poor4.
Therefore, it is believed that these patients have a higher risk of recurrence and metastasis.
How to improve their survival rate is a clinical problem that needs to be solved urgently.

PD-1 inhibitors are a new type of immunotherapy that relieves tumor cells from escaping the immune system.
Combined with radiotherapy and chemotherapy, they can synergistically kill tumors and show good efficacy in the treatment of nasopharyngeal carcinoma.

The results of the POLARIS-02 study showed that for the treatment of recurrent and metastatic nasopharyngeal carcinoma with teriprizumab, the ORR reached 20.
5%, and the median overall survival (OS) was 17.
4 months1.

In this case, after neoadjuvant treatment with teriprizumab, the curative effect of nasopharyngeal lesions reached CR, and the overall curative effect reached CR after radiotherapy and chemotherapy, indicating that immunotherapy combined with radiotherapy/chemotherapy has a better effect in the initial treatment of locally advanced nasopharyngeal carcinoma.
It has good application prospects, but further research is still needed to verify its efficacy.

It is hoped that further research can achieve positive research results and bring more benefits to patients with nasopharyngeal cancer! References: 1.
Feng-Hua Wang, Xiao-Li Wei, Jifeng Feng, et al.
J Clin Oncol.
2021 Mar 1;39(7):704-712.
2.
Shu-Zhen Lai, Wen-Fei Li, Lei Chen,et al.
nt J Radiat Oncol Biol Phys.
2011 Jul 1;80(3):661-8.
3.
Anne WM Lee,Wai Tong Ng,Lucy LK Chan,et al.
Radiother Oncol.
2014 Mar;110(3 ):377-84.
4.
Jin-Ching Lin, Wen-Yi Wang, Kuang Y Chen, et al.
N Engl J Med.
2004 Jun 10;350(24):2461-70.