Protecting the source and ensuring a sufficient amount of chemotherapy, traraciclib helps patients achieve excellent results!

Will triracicillide + chemotherapy be the preferred treatment for SCLC?

Lung cancer is the largest cancer in China, according to the 2020 global cancer burden data released by the World Health Organization's International Agency for Research on Cancer (IARC), the number of new lung cancer patients in China reached 820,000 in 2020, posing a serious threat to China's national health ^[1].

Although small cell lung cancer (SCLC) accounts for only about 15% of all lung cancers, this subtype of lung cancer has the characteristics of high malignancy, rapid proliferation, and easy to occur distant metastasis ^[2].

At present, chemotherapy is still the cornerstone of clinical treatment for SCLC, but chemotherapy can also cause adverse reactions such as bone marrow suppression in patients, which will affect the treatment of patients
' tumors.
In this issue of "Case Collection", Dr.
Meng Chong from Hainan Provincial People's Hospital shared the diagnosis and treatment of a case of advanced SCLC, which the editor sorted out in detail for readers
.

• General information

The patient, a 72-year-old female, came to our hospital for treatment with "cough for 2 months
".
On July 18, 2021, he was hospitalized in our department for "cough and sputum production for 2 months", and chest CT showed that "the left lung can be seen as a lumpy soft tissue mass shadow, lobulated, with a maximum section of about 8.
6cm×10.
5cm", and was admitted to the hospital
as "suspected lung cancer".

Anamnesis, family history: no special
.

Physical examination: superficial lymph nodes are not palpable, thoracic cage is not deformed, tactile speech in both lungs is normal, clear sounds on percussion in both lungs, clear breath sounds in both lungs, and no wet and dry rales
are heard.

• Ancillary examination

On July 16, 2021, contrast-enhanced CT showed that the left lung could be seen as a lump-like soft tissue mass shadow, lobulated, with a maximum cross-section of about 8.
6cm×10.
5 cm, multiple swollen lymph node shadows in both hilos and mediastinum, a small number of arc-like watery density shadows in the left chest cavity, some of which were wrapped, and multiple swollen lymph nodes in the hilar area of the liver (Figure 1).

Figure 1 Enhanced CT image of patient on July 16, 2021

Bronchoscopy on July 16, 2021: Mass infiltrates and grows at the distal left main bronchus and partially occludes the lumen (Figure 2).

Figure 2 Bronchoscopic image on July 16, 2021

Pathological testing showed that there were a few small cells
with deep nuclear nuclei between lung tissues.
Immunohistochemical test results showed TIF-1(+), CD56(+), CK(+), Vim (-), Ki-67(+, about 70%), LCA (-).

• Diagnosis: Left lung small cell lung cancer stage IV.
  B cT4N3M1c

  Metastasis of both hilar and mediastinal lymph nodes

  Multiple lymph node metastases in the hilar region of the liver

  Left pleural metastasis

According to the "Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Small Cell Lung Cancer", Dr.
Meng Chong chose the first-line treatment regimen
of etoposide combined with carboplatin for the patient.
Unfortunately, patients develop myelosuppression [white blood cell (WBC) grade II, neutrophil (NE) grade III]
after only one course of chemotherapy.
WBC decreased to 2.
71×10 9/L, absolute NE to 0.
79×10⁹/L, and NE percentage to 29.
2% (Table 1).

At this time, whether the use of granulocyte colony-stimulating factor (G-CSF) for patients or the adjustment of chemotherapy doses, it is bound to affect the patient's further antitumor therapy
.

Table 1 Data of the patient's test report on August 15, 2021

After various considerations, Dr.
Meng Chong included the patient in a real-world study exploring the clinical efficacy and safety of trilacillib, and provided the patient with the treatment regimen of triracillide combined with etoposide and carboplatin in the 2nd to 6th course of first-line chemotherapy, and once brought partial remission (PR) to the patient, and the patient did not experience myelosuppression during the subsequent treatment (Table 2-5).

From left to right: Table 2 Patient's test report data on August 24, 2021, Table 3 Patient's test report data on September 12, 2021, Table 4 Patient's test report data on September 15, 2021, Table 5 Patient's test report data on October 9, 2021

Expert reviews

Cytotoxic chemotherapy drugs are a class of drugs that target growing and proliferating active cells, inhibit the proliferation of tumor cells, and induce apoptosis
.
In addition to tumor cells, the growth of cells of organs or tissues such as bone marrow hematopoietic stem cells, digestive tract mucosa, skin and other organs or tissues in the human body is also more active, and if cytotoxic chemotherapy damages bone marrow hematopoietic stem cells, it will lead to multilineage myelosuppression ^[3].

Myelosuppression is the most common side effect of chemotherapy for tumors and is the dose-limiting toxicity of chemotherapy drugs ^[4].

According to relevant statistics, more than 80% of chemotherapy drugs can cause bone marrow suppression, and at the same time, 80% of patients will have myelosuppression during tumor radiotherapy ^{and chemotherapy [5,6].}

According to data, chemotherapy was used for the first anti-tumor treatment regimen for about 9.
8 million cancer patients worldwide in 2018, and this number is expected to reach 15 million by 2040 ^[7].

This shows the importance of chemotherapy in the treatment of tumors and the need
to find a way for patients to reduce the incidence of chemotherapy-induced bone marrow suppression (CIM).
Traracillide is a highly potent, selective, and reversible cell cycle-dependent kinase 4/6 (CDK4/6) inhibitor that can induce temporary arrest of hematopoietic stem/progenitor cells (HSPCs) in the G1 phase, reduce the damage of chemotherapy drugs to bone marrow cells, and thus reduce the incidence of CIM^[3].

Previously, the results of three randomized, double-blind phase II clinical studies G1T28-02, G1T28-05 and G1T28-03 showed that the use of traracillide in patients with extensive-stage small cell lung cancer (ES-SCLC) before receiving chemotherapy can reduce the duration of severe neutropenia (DSN) and the incidence of severe neutropenia (SN) in the first cycle after treatment ^[8-10].

。 The TRACES study led by Professor Cheng Ying of Jilin Cancer Hospital has proved that the pharmacokinetic characteristics, efficacy and safety of triracillide in domestic ES-SCLC patients are similar to those in foreign countries ^[11,12].

In addition, the current clinical treatment for CIM is often to alleviate the condition through therapeutic intervention after the occurrence of CIM, which cannot truly achieve the purpose of "protecting" the bone marrow, and the emergence of triracillide fills this gap
for the clinic.
At the same time, triracillide is also the world's first drug with a full range of bone marrow protective effects, which can provide patients with comprehensive bone marrow protection
.
The patient did not use traraciclib during the first course of chemotherapy and soon developed grade III neutropenia and grade II leukopenia
.
When the patient was given traracillide, the symptoms associated with myelosuppression improved significantly, the relevant indicators returned to normal levels, and the patient did not develop myelosuppression in subsequent treatment (Table 6).

At the same time, triracicillide did not cause the replacement or reduction of chemotherapy drugs in the patient, ensuring that the patient received a sufficient amount of chemotherapy and a full course of chemotherapy, thereby ensuring the efficacy and survival benefit
of the patient's anti-tumor therapy.

Table 6 Comparison of data before and after triracicillide

References

[1] https://gco.
iarc.
fr/

YU Tao, ZHONG Diansheng, Research progress in immunotherapy for small cell lung cancer[J].
Chinese Journal of Lung Cancer,2018,21(12),918-920.
)

[3] Li C, Hart L, Owonikoko TK, et al.
Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer.
Cancer Chemother Pharmacol.
2021, 87(5):689-700.

[4] Epstein RS, Aapro MS, Basu Roy UK, et al.
Patient Burden and Real-World Management of Chemotherapy-Induced Myelosuppression: Results from an Online Survey of Patients with Solid Tumors[J].
Adv Ther.
2020, 37(8):3606-3618.

[5] Expert Committee of Integrated Traditional Chinese and Western Medicine of Chinese Society of Clinical Oncology.
Expert consensus on the diagnosis and treatment of integrative medicine of integrative medicine caused by antitumor drugs caused by bone marrow suppression[J].
Journal of Clinical Oncology,2021,26(11):1020-1027.
)

FAN Kui, DAI Liangmin, WU Zhenfeng, et al.
Research progress on myelosuppression induced by chemoradiotherapy[J].
Chinese Journal of Traditional Chinese Medicine, 2017, 32(1):5.

[7] Wilson BE, Jacob S, Yap ML, et al.
Estimates of global chemotherapy demands and corresponding physician workforce requirements for 2018 and 2040: a population-based study[J].
Lancet Oncol.
2019, 20(6):769-780.

[8] Weiss JM， Csoszi T， Maglakelidze M， et al.
Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial[J].
Ann Oncol.
2019，30（10）:1613-1621.

[9] Daniel D， Kuchava V， Bondarenko I， et al.
Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre， randomised， double-blind， placebo-controlled Phase II trial [J].
Int J Cancer.
2020 ，148（10）:2557–70.

[10] Hart LL， Ferrarotto R， Andric ZG， et al.
Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized， Double-Blind， Placebo-Controlled Phase II Study[J].
Adv Ther.
2021，38（1）:350-365.

[11] Ying Cheng, Lin Wu, DingZhi Huang.
Myeloprotection with Trilaciclib in Chinese Patients with Extensive-Stage Small Cell Lung Cancer Receiving Standard Chemotherapy (TRACES).
2022 WCLC, Abstract EP08.
02-078.

[12] Y Cheng, L Wu, DZ Huang, et al.
Updated data of myeloprotective Effect of Trilaciclib  in Chinese Patients with Extensive-Stage Small Cell Lung Cancer  receiving Chemotherapy(TRACES).
2022 CSCO.