Cases Shenghui | Breaking with traditional treatments, anti-angiogenesis combined with immunity helps drive long-term survival of gene-negative advanced NSCLC

*Only for medical professionals to read for reference.
Recombinant human endostatin + chemotherapy + immunotherapy provides new treatment options for non-small cell lung cancer (NSCLC) patients with negative driver genes.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer.
Approximately 75% of patients are in the middle or advanced stage at the time of diagnosis, and the survival rate is low [1].

In recent years, immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibody have developed rapidly and have become an important treatment method in the field of lung cancer.
However, they still have certain limitations, such as low effective response rate, only a few Patients will eventually benefit from it, etc.
[2].

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

Anti-angiogenic drugs can enhance certain links in the tumor immune cycle and have a synergistic anti-tumor effect when used in combination with immunotherapy [2], which has become a major direction of exploration and research in the field of lung cancer.

In this issue of "case-by-case", a case of advanced NSCLC with multiple lymph node metastasis was shared.
Recombinant human endostatin combined with teriprizumab and chemotherapy were used to obtain a treatment case of stable disease (SD).

Basic information of the patient: A male, 57 years old, was admitted to the hospital on May 19, 2020 because of "the carcinoembryonic antigen was more than 4 months high in the physical examination".

History of present illness: The patient’s physical examination found more than 4 months before admission that carcinoembryonic antigen (CEA)>1040ng/ml, chest CT (January 15, 2020) showed: clusters of nodules in the middle lobe of the right lung, considering infectious lesions Possibly; small ground-glass nodules in the apical segment of the right upper lobe, and a few micro-nodules and miliary nodules in the left upper lobe.

Past history: The patient has a history of diabetes for 8 years, and a complete gastrointestinal endoscopy 10 days ago revealed esophageal polyps and colon polyps.

Personal history: more than 30 years of smoking history, 1 pack/day.

Post-hospital examination: physical examination: a 1cm*0.
6cm lymph node can be palpated on the right clavicle, which is of tough quality and moderate mobility.
The other superficial lymph nodes are not palpable and enlarged, and there is no obvious abnormality.

Whole-body PET-CT examination showed: multiple nodular and slightly higher metabolic foci in the lateral right middle lobe, considering malignant tumors, and multiple lymph node metastases in the mediastinum (groups 1R, 2R, 4R, 6R, 10R, and 10L); There are multiple small nodules in the lung, low metabolism; brain atrophy; postoperative changes in the middle esophagus; changes in the lower right lung; calcification of the left coronary artery; postoperative changes in the ascending colon; degenerative changes in the spine.

Bronchoscopy (May 20, 2019) showed: right middle lobe disease, 4R group lymph node disease.

Figure 1.
Bronchoscopy results of lymph node pathological biopsy (May 22, 2020) showed: (right neck lymph node) lymph node metastatic adenocarcinoma, combined with immunohistochemical results, considering lung origin.

Immunohistochemical results: CK7(+), CK20(-), Villin(-), TTF-1(+), Napsin-A(+), Ki67(40%+), P53 (abnormal expression-), Pax- 8(-), GATA3(-), P40(-), CK5/6(-), CDX-2(-).

Genetic testing: EGFR, ALK, ROS1, KRAS, BRAF were all negative, and PD-L1 TPS expression was negative.

Final diagnosis 1.
Right middle lobe adenocarcinoma (multiple lymph node metastases in both upper lungs, right hilar, mediastinum and right supraclavicular fossa cT4N3M1b IVA stage EGFR-ALK-ROS1-KARS-PD-L1 -); 2.
Diabetes; 3.
Fatty liver; 4.
After esophageal polypectomy; 5.
After colonic polypectomy; 6.
Chronic obstructive pulmonary disease; 7.
Thoracolumbar degeneration.

After treatment on June 19, 2020, July 10, 2020, July 31, 2020, and August 21, 2020, the patient was given recombinant human endostatin + teriprizumab + AC (peimer Trexed + carboplatin), after 2 cycles of treatment, chest CT curative effect was evaluated as SD, and SD persisted after 4 cycles.

Figure 2.
Recombinant human endostatin + teriprizumab maintenance treatment on the patient during the period from September 12, 2020 to March 13, 2021 after chest CT before treatment, after 2 cycles, and after 4 cycles9 cycle.

After 6, 8, 10, and 12 cycles, chest CT was performed to evaluate the curative effect, and the patient's continuous SD state can be seen.

Figure 3.
After 8 cycles, 10 cycles, and 12 cycles of treatment, the tumor marker CEA of chest CT patients continued to decline, as shown in the following figure: Figure 4.
The patient's tumor marker CEA change case provided by Professor Cai Zhiming, chief physician of the Department of Respiratory Medicine, Zhangzhou Hospital, Fujian Medical University Postgraduate tutor, Youth Committee of the National Respiratory Society, Member of the Standing Committee of the Respiratory Branch of the Zhangzhou Medical Association, Fujian Province, Director of the Clinical Oncology Diagnosis and Treatment Branch of the Fujian Strait Medical and Health Exchange Association, Deputy of the Rare Target Group of the Clinical Oncology Diagnosis and Treatment Branch of the Fujian Strait Medical and Health Exchange Association Member of the Standing Committee of the Respiratory Branch of the Hospital Association, Director of the Oncology Clinical Research Collaboration Branch of the Fujian Strait Cancer Prevention and Treatment Technology Exchange Association, Associate Professor of Fujian Medical University, Outstanding Faculty Teacher of Fujian Medical University, Director of the Respiratory Medicine Branch of Fujian Strait Medical and Health Exchange Association The application has increased the 5-year survival rate of advanced lung cancer from less than 5% to 26%, and it plays an increasingly important role in the first-line and second-line treatment of NSCLC.
However, in clinical applications, immunotherapy still has low efficiency and low gains.
The problem of limited beneficial population and lack of accurate markers [3].

In response to these problems of immunotherapy, more new immunotherapy models are constantly being explored and applied [3].

As we all know, angiogenesis is a key link in the growth, recurrence and metastasis of primary tumors.

Preclinical data show that anti-angiogenic drug therapy can increase the infiltration of immune cells into tumors, improve tumor hypoxia and the inhibitory state of tumor immune microenvironment; and the anti-tumor immune response activated by immunotherapy can also normalize blood vessels.
, To build a positive feedback pathway in anti-angiogenesis [4,5].

Therefore, for the treatment of patients with advanced NSCLC, the combined use of anti-angiogenic drugs and immunotherapy may achieve the effect of 1+1>2 [6], and a variety of imported and domestic PD-1/L1 inhibitors have been approved.
Actively carry out relevant research. The Enpower study published in 2020 showed that recombinant human endostatin combined with standard platinum-containing dual-drug chemotherapy (pemetrexed + carboplatin/cisplatin) and sintilizumab for first-line treatment of patients with advanced non-squamous NSCLC with negative driver genes The objective response rate (ORR) was 72%, and the ORR of the control group was 66%.

The study suggests that recombinant human endostatin + chemotherapy + immunotherapy is expected to solve the problem of low objective remission rate of immunotherapy.

The patient in this case is a stage IV driver gene-negative NSCLC patient who was treated with recombinant human endostatin + teriprizumab + AC for 2 cycles and then obtained SD, and continued to use recombinant human endostatin + teripril Anti-maintenance treatment, the patient continues to be in the SD state, and the treatment effect is obvious, confirming the exact effect of recombinant human endostatin combined with immunization and chemotherapy in patients with stage IV driver gene-negative lung cancer.

We also look forward to the further exploration of recombinant human endostatin combined immunization and chemotherapy in the field of NSCLC, which will bring more benefits to patients.

References: [1] Geng Zhenying.
Clinical analysis of 2440 cases of non-small cell lung cancer D].
Nankai University, 2013.
[2] Research progress of anti-angiogenesis therapy combined with immune checkpoint inhibitors in NSCLC[J].
Chinese Journal of Microecology, 2018, 030(011):1350-1353.
[3] Wu Fengying, Zhou Caicun.
Lung Cancer Immunity Current status and future prospects of treatment[J].
Chinese Journal of Oncology Surgery, 2020, Volume 12, Issue 3, Pages 185-187, CA, 2020.
[4] Tian L, Goldstein A, Wang H, et al.
Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming[J].
Nature, 2017, 544(7649): 250-254.
[5]Huang Y, Kim BYS, Chan CK, et al.
Improving immune–vascular crosstalk for cancer immunotherapy[J].
Nature Reviews Immunology, 2018, 18(3): 195-203.
[6]Manegold C, Dingemans AMC, Gray JE, et al.
The potential of combined immunotherapy and antiangiogenesis for the synergistic treatment of advanced NSCLC[J].
Journal of Thoracic Oncology , 2017, 12(2): 194-207.