2.5 million a year? First 'broad-spectrum' anticancer drug approved in China, proven to treat a variety of cancers

In the world, precision therapy is a major trend in anti-cancer, and the development and introduction of special targeted drugs can fill the gap in the Chinese market.

On April 13, 2022, the official website of the State Drug Administration showed that the " Larottinib Sulfate Capsule Marketing Application " submitted by Bayer has been approved. This means that China has ushered in the first pan-solid tumor targeting drug (TRK inhibitor) larotrectinib for NTRK gene fusion , which is a boon for many Chinese tumor patients.

As early as 2018, larotrectinib was approved by the US FDA under accelerated approval, becoming the first FDA-approved "broad-spectrum" targeted drug .

On May 26, 2021, Larotrectinib Sulfate Capsules obtained the priority review qualification of the State Drug Administration , and it was unexpectedly approved in less than a year, which is of great significance to the Chinese pharmaceutical industry and cancer patients .

1. What is the "magic" of larottinib

Larotrectinib is a targeted drug specifically for the treatment of tumors with NTRK gene fusions .

The NTRK gene can be fused with other genes to produce abnormal proteins (TRK fusion proteins) that promote tumor growth and spread . Taking advantage of this feature, larotrectinib can strike precisely and produce anti-cancer effects.

NTRK gene fusions can be found in a variety of solid tumors , including thyroid cancer, salivary gland cancer, breast cancer, colorectal cancer, lung cancer, pancreatic cancer, etc. Especially in rare cancers such as infantile fibrosarcoma, breast-like secretory carcinoma, and breast-secretory carcinoma, the incidence of NTRK gene fusion is as high as 90%.

Therefore, larotrectinib, as the first oral TRK inhibitor, has broad-spectrum antitumor activity.

2. Filling the gap for domestic precision tumor therapy

Clinical trials are the only way for a drug to be approved, and the three large-scale clinical trials of larottinib have all given gratifying results.

As of July 2020, 218 patients with NTRK gene fusion-positive cancers had been treated with larotrectinib, of whom 206 were evaluable for efficacy, including 21 different tumor types .

The data showed that the overall response rate of larotrectinib was 75% , including 45 patients with complete response , 109 patients with partial response, 33 patients with stable disease, and 13 patients with disease progression to the best response . Among all evaluable patients, the median time to optimal response was 1.8 months , and the median duration of response was 32.9 months .

In the trial, treatment-related adverse events were mainly grade 1-2 , indicating that larotrectinib has excellent efficacy and safety.

Professor Zhou Caicun of Shanghai Pulmonary Hospital Affiliated to Tongji University said that the official approval of larotrectinib in China is of great significance, which not only further improves the efficacy and prognosis of patients with NTRK gene fusion positive tumors, but also fills the gap for precise treatment of patients with NTRK gene fusion tumors. blank.

3. What cancers can larotrectinib be used for?

The latest trial data show that the types of cancers suitable for larotrectinib have increased from 17 to 21 , covering almost all solid tumor types.

Specifically include soft tissue sarcoma, infantile fibrosarcoma, primary central nervous system tumors, thyroid cancer, salivary gland cancer, lung cancer, colorectal cancer, melanoma, colon cancer, breast cancer, gastrointestinal stromal tumor, osteosarcoma, bile duct cancer, pancreatic cancer, congenital mesodermal renal cancer, primary unknown cancer, appendix cancer, liver cancer, prostate cancer and cervical cancer, etc.

At present, the domestically approved indications are:

Adult and pediatric solid tumors harboring an NTRK fusion gene and excluding known acquired resistance mutations;

Locally advanced, metastatic disease, or surgical resection of adult and pediatric solid tumors that may lead to serious complications;

· Adult and pediatric solid tumors without satisfactory alternative therapy or failure of previous therapy .

Fourth, these questions, you may want to know

Q1: Is there any drug resistance?

As a targeted drug, larotrectinib also has drug resistance, which is mainly related to the new mutation of the NTRK gene in patients . For the resistance of larotrectinib, the second-generation TRK-targeted drugs have come out. If new resistance sites are discovered in the future, scientists still need to solve them.

Q2: Do I need genetic testing?

At present, the detection methods of NTRK gene fusion mainly include the following four:

Immunohistochemistry (IHC) : It is widely available, low cost, and can be reimbursed, but its specificity is limited and can only be used as primary screening.

Fluorescence in situ hybridization (FISH) : It has high sensitivity and specificity, uses few samples, and has low requirements for tumor purity, but requires fluorescence microscopy and cannot determine the fusion partner.

Reverse Transcription Polymerase Chain Reaction (RT-PCR) : High sensitivity and specificity, can detect gene fusions expressed at the RNA level with low cost. The disadvantage is that the target sequence must be known, and new fusion partners cannot be detected.

DNA- and RNA-based next-generation sequencing (NGS) : With high sensitivity and specificity, it can detect novel fusion partners and simultaneously detect multiple targetable therapeutic targets. The disadvantage is that it takes a long time (1-3 weeks) and the cost is higher.

Q3: When can it be used? How much does that cost?

Generally speaking, a new drug cannot be directly sold after it is approved for marketing. It is necessary to conduct trial observation and record the trial effect of the drug. Only through the trial and observation stage can merchants conduct mass production and put them on the shelves. It takes about 3-5 months from approval to purchase .

As for the price, larottinib is priced at $32,800 per month in the United States, or about 2.5 million yuan per year . At present, the domestic price has not been determined, and I hope it will not be too expensive, so that more patients can afford it.

The launch of new anti-cancer drugs is great news for cancer patients and their families. I hope more anti-cancer methods will appear in the future to benefit the common people.

References:

[1] "Unlimited tumor type" targeted drug larottinib has been approved in China, and domestic tumor precision treatment will be a new edge! .Medical Oncology Channel, 2022-04-17

[2] The clinical data of larotrectinib in the treatment of lung cancer are eye-catching, filling the gap for the precision treatment of lung cancer. China Medical Tribune, 2022-04-13

[3]Hong DS， Shen L， Van Tilburg CM， et al. Long-term efficacy and safety of larotrectinib in an integrated dataset of patients with TRK fusion cancer. J Clin Oncol. 2021;39(suppl 15)：abstr 3108. doi：10.1200/ JCO.2021.39.15_suppl.3108

Reproduction is prohibited without the author's permission