Baiguo's approximately "immune +" program, break the traditional treatment pattern of advanced lung cancer

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Baiguo's approximately "immune +" program, break the traditional treatment pattern of advanced lung cancer

2022-01-15 12:07:26 6 ℃

Lung cancer is one of the most common malignancies, morbidity and mortality of cancer ranks first. Emergence of immunotherapy, gradually improve the treatment outcome in patients with lung cancer during the traditional chemotherapy. Natalizumab for Reilly is currently the only one in the Fc segment for a special genetically engineered PD-1 monoclonal antibody, is currently the world's second, the first comprehensive domestic first-line squamous and non-squamous non-small cell lung cancer (NSCLC) ⅲ clinical study of successful registration of PD-1 antibody, while studies in small cell lung cancer (SCLC) field also achieved initial results, showing a good prospect. Recently re-transmission of good news for Raleigh daclizumab, following the beginning of this year into the health insurance drug list, which also successfully supplement lung cancer indications to enter the new national medical insurance catalog, the future will make more lung cancer patients enjoy the innovations brought about by the national health bonus , high-quality long-lived! This issue will share one cases of advanced squamous cell carcinoma and one patient with advanced small cell lung cancer treatment after first-line therapy are used "immune +" treatment, and are harvested good effect. (Cases a country to share and comment Professor Watson, Case II share and comment Professor Lin Xinqing).

Case

To Professor Imperial

MD, deputy director of oncology physician

First Affiliated Hospital of Guangzhou Medical University

Chinese Anti-Cancer Association, Guangdong Province Anti-Cancer Association members

Member of the Guangdong Provincial Institute of Chest Disease Professional Committee of lung cancer MDT

Guangdong Provincial Institute of Chest Disease tumor Intensive Professional Committee of the Standing Committee

Guangdong Provincial Institute of lung cancer precision medical applications branch members

Professional Committee tumor support and rehabilitation Guangzhou Anti-Cancer Association

Professional Committee of the World Federation of Chinese Medicine Societies palliative care for cancer research

A basic case information

General information: male patient, 76 years old, in 2020, July 1 treatment.

Chief complaint: recurrent cough, sputum more than 1 year.

Past medical history: chronic obstructive pulmonary disease and a history of 20 years.

Personal history: who metallurgical factory workers; smoking history of 50 years, 20-40 cigarettes / day, treatment to quit smoking before March; long-term drinking, wine about 100-150g / day.

Family history: father because of "consumption" died.

ECOG PS score: 1 point, NRS score: 0.

Whole body PET-CT (July 2020): soft tissue leaf basal segment of the left lower lobe mass, glucose metabolism was significantly higher, consider lung cancer involving the left oblique fissure pleura, perifocal a little obstructive inflammation, left hilar lymph nodes slightly increased glucose metabolism slightly elevated, not excluding the transfer. Figure 1-1.

Figure 1-1 treatment baseline PET / CT

Bronchoscope biopsy: lung compliance nonkeratinizing squamous cell carcinoma. Immunohistochemistry: CK (+), CgA (-), Syn (-), TTF1 (weak +), CD56 (-), Ki67 (hot spot about 60% +), NapsinA (-), P40 (+), P63 (+), PDL-1 (22C3) (-), PDL-1 (Neg) (-). As shown in Figure 1-2.

FIG bronchoscope biopsy 1-2

Genetic Testing: No drive common mutation, VEGFR-TKI may be sensitive, TMB-H, immunotherapy may be sensitive.

Pulmonary function: mixed severe pulmonary dysfunction.

Diagnosis: left lung squamous involving a left oblique fissure left hilar lymph node metastases and pleural (cT3N1M0 ⅢA s) 2 3. chronic obstructive pulmonary disease with severe mixed ventilation dysfunction.

After a diagnosis and treatment of patients

Line treatment: immune anti-angiogenic + chemotherapy + radiotherapy +

Treatment: Patients from 7 August 2020 to 12 October 2020 applications for Raleigh trastuzumab + paclitaxel albumin + platinum + Nida recombinant human endostatin treatment for 4 cycles. 2020 December 14 to January 26, 2021 chest lesions radical radiotherapy (SBRT) 65Gy / 33F. Since January 27, 2021 start giving patients for Raleigh natalizumab + recombinant human endostatin therapy, has completed 13 cycles.

Treatment: Patients from 7 August 2020 to 12 October 2020 applications for Raleigh trastuzumab + paclitaxel albumin + platinum + Nida recombinant human endostatin treatment for 4 cycles. 2020 December 14 to January 26, 2021 chest lesions radical radiotherapy (SBRT) 65Gy / 33F. Since January 27, 2021 start giving patients for Raleigh natalizumab + recombinant human endostatin therapy, has completed 13 cycles.

Imaging and Evaluation: periodic review of the treatment period the patient's chest CT, last follow-up time was 21 December 2021, showing left lung lesions continue to shrink (Figure 1-3), to assess the efficacy of sustained partial remission (PR) .

FIG treatment during 1-3 chest CT Dynamic Change

Safety Evaluation: Immune combined chemotherapy and anti-angiogenesis right lower pneumonia patients had occurred after 4 treatment cycles, the anti-infection pneumonia 2 weeks after treatment improved, shown in Figure 1-5. I no obvious adverse reactions.

1-5 dynamic changes during treatment of pneumonia in the lower right of FIG.

A case summary

In this case, the patient is the old man, the main reason for "repeated cough, cough more than 1 year". Combined with symptoms, imaging and biopsy pathology, etc. Since January 27, 2021, immunized anti-angiogenic treatment has been used to complete 13 cycles. During treatment, check chest CT during treatment, the lower left lung lesion continued to shrink, and the efficacy was evaluated as a persistent PR. After 4 cycles of immune combination chemotherapy, patients have had upper right lower pneumonia, and the symptoms are improved after anti-infection treatment, and there is no significant adverse reactions. Expert Expert Review

Squamous carcinoma is one of the common types of NSCLC, which occurs in elderly men, which is closely related to smoking, and more than 70% of patients have been in phase III / IV. As in this case, a diagnosis has been diagnosed with pulmonary squamous carcinoma IIIa, the lesion is tired and the left slope pleura and the left lung gate lymph node metastasis. The patient is poor, considering that it may be mechanical and ventilated after surgery, even if it can smoothly extract the quality of life, surgery is not recommended after comprehensive assessment. Patients with advanced lung squamous cell carcinoid cancer for such can't surgically resection, the current clinical mainly with platinum double drug chemotherapy is a first-line treatment plan, but the effect is not ideal, the median PFS and median OS are only 6.3 months and 12.1 Month [1]. At the same time, due to the low occurrence rate of the drive gene, it is relatively small for targeted therapy in terms of lung adenocarcinoma and pulmonary squamous cell carcinoma [2]. In recent years, the rise of immunological examination points inhibitors have opened up new ideas for advanced pulmonary squamous cell carcinoma treatment.

Keynote 407 studied the door of advanced pulmonary squamous cell carcinoma immunization chemotherapy, established immunotherapy, combined with chemotherapy, in advanced pulmonary squamous cell carcinoma first-line treatment [3]. Rational 206 studies initially verified the effectiveness of my country's independently developed tidarel combined withdrawal treatment of lung squamous cell carcinoma [4]. Subsequent stage III clinical research (Rational 307) [5] Continue to explore the first-line treatment of toldley bead combined with traditional chemotherapy solution (paclitaxel / albumin paclitaxel + carboplatin) Effectiveness and safety. Comparative traditional chemotherapy solution, telleley bead combination chemotherapy can significantly improve the patient without progress (PFS) (7.6 months / 7.6 months vs 5.5 months), improve the objective relief rate (ORR) (72.5%) (72.5%) / 74.8% vs 49.6%), improve the patient's continuous mitigation time (DOR) (8.2 / 8.6 months vs 4.2 months). Regardless of the level of expression of PD-L1, each subgroup is unanimously benefiting and has good safety. Based on the pre-period data of the study, January 12, 2021, the Trighley Baby combined with chemotherapy has also officially obtained the first-line treatment of the National Drug Administration (NMPA) for advanced pulmonary squamous cell carcinoma, and related indications It has recently been added to enter the latest version of the medical insurance drug catalog in my country.

In addition, the study of immune combined anti-angiogenic treatment in the NSCLC field has also progressed. Recombinant human vascular endothelin can promote normalization of tumor blood vessels, improve lane, reduce leakage and tissue gap pressure, improve drug delivery, inhibit tumor cell migration, and improve the sensitivity of radiotherapy. Recombinant human vascular endothelial inhibitors can also reverse the immunosuppressive state of the tumor microenvironment, synergistic immunotherapeutic function [6-9]. The PD-1 inhibitor can activate the effect T cells to further promote normalization of tumor angiogenesis. The two are combined to form a positive feedback loop between blood vessels and immunization, and can achieve a better tumor killing effect [10]. Related animal model experiments have confirmed that recombinant human vascular endothelial inhibitory PD-1 antibodies can significantly inhibit the growth of lung cancer in mice [11].

Based on the above studies, the first-line treatment of this patient adopts the telleley beads + albumin paclitaxel + Nada Platinum + Recombinant human vascular endothelial inhibitory solution. After 4 cyclic treatment, the tumor was significantly retracted, and the efficacy was evaluated as Pr. Subsequent patients received radiotherapy for chest, and the efficacy continued PR. Since then, the patient adopted immunization of anti-angiogenic maintenance, a total of 13 cycles, still maintaining PR curative effect, and the patient remarkably benefited. After 4 cyclancing of immune combination chemotherapy, patients have had pneumonia, and the symptoms have improved after anti-infection treatment, and there is no significant adverse reactions, the overall safety and tolerance of treatment. This "triple treatment" of immunization + chemotherapy + anti-angiogenic treatment provides a new treatment idea for patients with advanced NSCLC. However, the research exploration in this field is still in its infancy, and a large amount of data acquisition and clinical analysis research in the future. Looking forward to the future "triple treatment" solution can be pushed to the front line, making more patients benefit.

Two cases

Forest mood professor

Respiratory and severe medical department

First Affiliated Hospital of Guangzhou Medical University

Guangzhou Respiratory School of Health

National Respiratory Medicine Center

Deputy Chief Physician, Master Tutor

Guangzhou Anti-Cancer Association Cancer Micro Environment Embroidered Committee

Commission on the Pulmonary Rehabilitation Professional Committee of China Disabled Rehabilitation Association

Member of the Tumor Immunization Professional Committee of China and Western Medicine Association

Guangzhou Anti-Cancer Association Lung Cancer Professional Committee

Standing Committee of the Lung Cancer Branch of Guangdong Precision Medical Application Society

Professional Committee of the National Committee of pulmonary nodules minimally invasive tumor minimally invasive treatment of industrial technology innovation and strategic alliances Lung Cancer Prevention Coalition, China Youth Committee

Members of the Youth Committee of the Chinese breathing Cooperative Oncology Group

Case II Basic Information

General information: male patients, aged 51, 2020. February 21 visits.

Chief Complaint: cough, shortness of breath a few months.

History of present illness: The patient a few months ago due to "cough, shortness of breath," treatment, after treatment of anti-infective therapy, after the chest CT, PET-CT and other tests may consider the lower right lung.

Past history and personal history: No special.

Pathology (2020, March 2): small cell lung cancer.

Immunohistochemistry: CK (+), A (+), Sxm (+), TTF1 (+), LCA (-), CD56 (+), Ki67 (90% +), PDL-1 (22C3) (-) , PDL-1 (NE) (-). Figure 2-1.

FIG pathological image 2-1

PET-CT examination (21 February 2020) shows: the lower right lung. Figure 2-2.

Figure 2-2 treatment baseline PET / CT

Diagnosis: small cell lung cancer.

Case II After treatment

Line treatment: chemotherapy, immune +

Treatment: Patients from 2020 March 4 to September 12 line platinum + etoposide + spring for Raleigh natalizumab for 8 cycles. The second line period cycles of treatment chest drainage and injection of recombinant human endostatin in the thoracic cavity. Patients on 17 October 2020 for Reilly began using natalizumab therapy, it has completed a total of 11 cycles.

Treatment: Patients from 2020 March 4 to September 12 line platinum + etoposide + spring for Raleigh natalizumab for 8 cycles. The second line period cycles of treatment chest drainage and injection of recombinant human endostatin in the thoracic cavity. Patients on 17 October 2020 for Reilly began using natalizumab therapy, it has completed a total of 11 cycles.

Imaging and Evaluation: periodic review of the treatment period the patient's chest CT, see right lower lung lesions continue to shrink. Efficacy assessments PR. 2-3 shown in FIG.

Right lower lung lesions dynamic changes during treatment Figure 2-3

Safety Evaluation: appears during treatment in patients with generalized weakness, muscle aches, shortness of breath after the event; I no obvious adverse reactions.

Case II summary

The patients were middle-aged men, with a history of test results, imaging studies, etc., a clear diagnosis of small cell lung cancer. Immunohistochemical first-line treatment in combination with chemotherapy 9 cycles. During the second period to be the treatment of thoracic drainage and injection of recombinant human endostatin in the thoracic cavity. Patients in 2020 October 17 began with a single drug immunotherapy, has completed a total of 11 cycles. During the regular review of the treatment of chest CT see lesions continue to shrink, to assess the efficacy of PR. During treatment the overall good safety.

Case II Experts

Lung cancer is one of the most common malignancies, morbidity and mortality of cancer ranks first. Small cell lung cancer (SCLC) about 15% of all lung cancers, strong an aggressive, rapidly proliferating cancer. SCLC patients with poor prognosis, about two-thirds of newly diagnosed patients with extensive-stage disease has reached, the average 5-year survival rate of less than 1% of these patients [12-13]. Although SCLC sensitive to radiotherapy and chemotherapy, but prone to drug resistance and limited after drug treatment. As turned out to immunotherapy, SCLC treatment ushered in new opportunities.

IMpower133 results showed that first-line treatment in combination with chemotherapy immune extensive stage SCLC can significantly prolong OS and PFS [14]. Immune CASPIAN studies in combination with chemotherapy first-line treatment mode also brings the same benefit for patients with extensive-stage SCLC, OS is a breakthrough 13 months [15]. my country has independently developed for Raleigh natalizumab also showed significant efficacy and safety in the field of SCLC. Research (RATIONALE 206 study) queues Ⅱ lung cancer in combination with chemotherapy for the Rayleigh line natalizumab therapy, 17 SCLC patients receiving daclizumab for Rayleigh + etoposide + cisplatin / carboplatin, 16 lesion reduction was observed in 13 cases (77%) of the evaluation reaches reconfirmed PR, ORR up to 76.5%, median PFS was 6.9 months, the median OS of 15.6 months [16]. Clinical studies (BGB-A317-312 Research) Ⅲ of extensive-stage SCLC line to carry out follow-up treatment has been completed into the group and look forward to the results released early, as natalizumab for the treatment of SCLC Raleigh provide reliable evidence based medicine.

The patients were middle-aged men, with a history of test results, imaging studies, etc., a clear diagnosis of small cell lung cancer. The use of first-line treatment for Raleigh natalizumab in combination with chemotherapy. Studies have shown that immune checkpoint inhibitor able to activate effector T cells, promote the normalization of tumor blood vessels, improve the immune microenvironment also greatly enhance the killing effect of immune cells to the tumor. Therefore, the first-line treatment of patients with immune therapy combined with chemotherapy 9 cycles. And subsequent immune monotherapy using 11 cycles. During the regular review of the treatment of chest CT see lesions continue to shrink, to assess the efficacy of sustained PR. During treatment the overall good safety.

The case was confirmed from the perspective of clinical practice, the huge potential of the treatment of toldlley beads in the treatment of SCLC. At present, the exploration of tutalel-beam combined with SCLC first-line treatment is in full swing, expecting related results to be transformed into clinical, and bring more drug options for lung cancer patients. More exciting

references:

[1] Socinski MA, Bondarenko I, Karaseva NA et al Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer:. Final results of a PHASE III Trial. J. Clin. Oncol. 30 (17), 2055-2062 (2012).

[2] AN SJ, CHEN EN, Su J et al. Identification of Enriched Driver Gene Alterations In Subgroups of Non-Small-Cell Lung Cancer Patients Based On Histology and Smork Status. Plos One 7 (6), E40109 (2012).

[3] Luis Paz-Ares, et al. J Thorac Oncol, 2020, 15 (10): 1657-1669.

[4] WANG Z, ZHAO J, MA Z, ET Al. A Phase 2 Study of Tislelizum IN Combination With Platinum-based Chemotherapy As First-Line Treatment for Advanced Lung Cancer in Chinese Patients [J]. Lung Cancer. 2020, 147 : 259-268.

[5] JIE WANG, SHUN Lu, ET Al. Jama Oncol, 2021, 7 (5): 709-717.

[6] Monitoring the process of endostar-induced Tumor Vascular Normalization by Non-Contrast Intravoxel Incoherent Motion Diffusion-Weight MRI [J]. Front Oncol, 2018, 8: 524.

[7] Effect of recombinant human endostatin on radiosensitivity in patients with non-small-cell lung can Cancer [J]. Int J Radiat Oncol Biol Phys, 2012, 83 (4): 1272-7.

[8] Polarization of Tumor-Associated Macrophage Is Associated with Tumor Vascular Normalization by endostatin [J]. Thracic Cancer, 2013, 4 (3): 295-305.

[9] Endostatin REVERS IMMunosuppression of the Tumor Microenvironment In Lung Carcinoma [J]. Oncology Letters, 2018, 15 (2): 1874-1880.

[10] Improving Immunotherapy Outcomes with anti-angiogenic Treatments and vice versa [j]. Nat Rev Clin Oncol, 2018, 15 (5): 310-24.

[12] Kalemkerian GP, Schneider B J. Advances in Small Cell Lung Cancer [J]. Hematol Clin N AM, 2017, 31 (1): 143-156. [13] Kalemkerian GP, Akerley W, Bogner P, ET ALSMALL Cell Lung Cancer [J]. J NATL COMPR CANC NETW, 2013, 11 (1): 78-98.

[14] Pacheco J, Bunn Pa. Advancements in Small-Cell Lung Cancer: The Changing Landscape Following Impower-133. Clin Lung Cancer. 2019, 20 (3): 148-160.

[15] Paz-Ares L, et al.Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial2019, 394 (10212): 1929-1939.

[16] Liu Sy, Wu Yl. Tislelizumab: An InvestiGational Anti-PD-1 Antibody for the Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC). EXPERT OPIN Investig DRUGS. 2020, 29 (12): 1355-1364.