WCLC2020 attacks on the precision treatment of lung cancer, to see what the breakthrough of the popular targets

The World Lung Cancer Congress (WCLC), the world's largest multidisciplinary oncology conference dedicated to lung cancer and other chest malignancies organized by the International Lung Cancer Research Association (IASLC), has been postponed since the outbreak and will be held online virtually from 28 to 31 January 2021.
the second highest incidence of lung cancer, the mortality rate is still the first, lung cancer is the world's highest incidence of malignant tumors.
recently, the World Health Organization's International Agency for Research on Cancer (IARC) released the latest global cancer data, which shows the latest morbidity, mortality and cancer trends for 36 types of cancer in 185 countries around the world.
, the number of new breast cancers (2.26 million) surpassed lung cancer (2.21 million) for the first time, making it the world's largest cancer.
new global cancer cases by 2020 (Photo: WHO), lung cancer will account for 1.8 million of the 9.96 million cancer deaths worldwide by 2020, with lung cancer accounting for 1.8 million more deaths than any other type of cancer.
, lung cancer remains the number one cause of death among new cancers and cancer deaths in men.
is worth noting that China ranks first in the world in terms of both new cancer and cancer deaths.
, lung cancer is still the leading cause of cancer-related deaths in China.
lung cancer is divided into two main types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), of which NSCLC accounts for about 85% of all lung cancer cases and SCLC accounts for 15%.
most lung cancer patients are terminally diagnosed and may die within one to two years without the right precision therapy.
In the field of lung cancer, in recent years, PD-(L)1 mono-resistant immunotherapy has been successful in the field of lung cancer, especially NSCLC, and other types of immunotherapy continue to dominate lung cancer news, including combination therapy.
but for more than a decade, research on targeted treatment for lung cancer has been in full swing, and has successfully developed a model of driven gene therapy that gives different drugs precision therapy based on mutation types.
current clinical practice, the main gene variants in lung cancer include: EGFR, ALK, ROS1, BRAF, MET, RET, KRAS, HER2, etc.
treatment strategies based on these targets have also been widely developed.
the WCLC conference, multiple targeted drugs will bring the latest research data.
RET: There are two RET inhibitors on the market worldwide, and there are three main mechanisms for abnormal activation of the primary cancer gene, including RET gene fusion, RET gene mutation and RET gene over-expression.
ret-activated fusion and mutations are key disease drivers for many cancer types, specifically reT mutations account for up to 65% of patients with advanced thyroid myelin-like cancer (MTC), and RET fusion is found in thyroid papyroid cancer (P) TC) accounts for about 10-20% of NSCLC patients and 1-2% of NSCLC patients, although its share in NSCLC patients may seem small, but because of the large base of this adaptive disorder, such patients are not uncommon in clinical treatment.
, the FDA has approved two RET gene variant targeting drugs, the Selpercatinib (LOXO-292) approved for listing in May 2020 and the Gavreto (pralsetinib, Platini), which was approved for listing in September.
Retevmo (selpercatinib, LOXO-292) was originally developed by precision therapy company Loxo Oncology, which was bought by pharmaceutical giant Eli Lilly for $8 billion in early 2019 and is currently approved for treatment of three types of tumors, RET fusion-positive NSCLC and thyroid cancer, and RET mutant MTC.
Gavreto (pralsetinib, Platinib) was developed by Blueprint Medicines and is currently approved by the FDA for three adaptations for the treatment of RET fusion-positive NSCLC adult patients, advanced or metastatic RET mutation MTC patients over 12 years of age who require systemic treatment, and patients who require systemic treatment with radioactive iodine incurable advanced or metastatic RET fusion-positive thyroid cancer.
addition, in May 2020, the European Medicines Agency (EMA) accepted applications for the listing of Platinib's treatment of NSCLC.
In China, Cornerstone Pharmaceuticals is committed to creating a pipeline of products that support sustainable growth, actively locating new targets, developing the first-of-its-kind, best-in-class cancer treatments, and has obtained exclusive development and commercial licensing of several of its targeted drugs, including Platini, in Greater China, including Chinese mainland, Hong Kong, Macau and Taiwan.
currently, Keystone Pharmaceuticals has submitted a listing application to the National Drug Administration (NMPA) for platini's treatment of RET fusion-positive NSCLC patients with platinum-containing chemotherapy, which was accepted and included in the priority review on September 7, 2020.
approved, it would be the first RET-targeted therapeutic drug to go on sale in China.
note that by the end of September 2020, the drug had taken the lead in landing in Boao Le City, Hainan, China.
it is understood that in 2021, Keystone Pharmaceuticals is expected to promote the approval of four products, including platinib, covering gastrointestinal mesothelioma, lung cancer, acute myeloid leukemia and more than four adaptations.
the WCLC conference, the two listed RET inhibitors published NSCLC patient research data in China and East Asia, respectively.
china study data from The Platini Global Phase I/II ARROW Key Study: 37 studies (32 central imaging can be evaluated) from RET fusion-positive late NSCLC patients in 10 centers in China, about half of whom (48.6%) had received ≥3 systematic treatments.
this is the first time that data on the efficacy and safety of PLAT fusion-positive NSCLC Chinese patients have been published after a failed platinum-containing chemotherapy, consistent with data previously reported in the GLOBAL population of the ARROW trial.
effectiveness, Platini showed strong activity against RET fusion-positive NSCLC after platinum-containing chemotherapy, with an objective remission rate (ORR) of 56 percent, a complete remission (CR), 17 partial remission (PR), 2 patients with PR status to be confirmed, and 13 patients with stable tumors and a disease control rate (DCR) of 96.9 percent.
as of the data cut-off date, the mid-mitigation duration (DOR) has not been reached.
safety, Platini has shown good tolerance and controlled safety, and there have been no adverse events associated with Platini that have led to death.
Selpercatinib's Global Multi-Center Phase I/II Clinical Study LIBRETTO-001: The study included 40 RET fusion-positive East Asian NSCLC patients who had previously received systemic therapy, including platinum chemotherapy, multi-kinase inhibitors, and anti-PD-(L)1 therapy.
found that ORR was 60%, with a medium follow-up of 12 months, and not a medium DoR.
good resistance to safety, consistent with previously reported LIBRETTO-001 results, and no new safety signals were found.
EGFR: The new strategy EGFR for classic targets is a cell proliferation and signal conduction of endosperm growth factor (EGF) and is a member of the skin growth factor (HER) family, which includes HER1 (erbB1, EGFR), HER2 (erbB2, NEU), HER3 (erbB3) and 4 (erbB4).
EGFR mutation is the most common mutation type in patients with late NSCLC, accounting for about 50%.
based on this path, scientists have made a lot of contributions, and several targeted drugs based on this target have been approved at home and abroad, and have under been revolutionized for generations.
EGFR gene mutations exist in dozens of subtypes, in addition to the common 19del and 21-L858R, including other rare mutations, which exist between 18 exons and 21 exons.
the WCLC conference, a variety of treatment strategies based on this target will be announced, including targeted drugs and dual-specific antibodies.
Mobocertinib (TAK-788): Small molecule EGFR/HER2 inhibitor study targeting EGFR20ins mutation was included in 96 patients with local late EGFR20ins mutation NSCLC, with a medium treatment time of 6 In .5 months, the ORR was 32%, the medium progression-free lifetime (PFS) was 7.3 months, and in patients pretreated with platinum drugs, the medium treatment time was 7 months, the ORR was 35% and the medium PFS was 7.3 months.
12-month PFS rate was 33%.
Amivantamab (JNJ-6372): EGFR/c-MET dual-specific antibodies were in the pre-treatment queue for platinum chemotherapy, with a medium follow-up time of 6.5 months and ANR of 36%, and all respondents received PR, The clinical benefit rate was 73%, the medium DOR was 6.8 months, 18 of the 29 effective patients had a continuous response (up to 16 months or more), the medium PFS was 8.3 months, and the medium total survival period (OS) was 22.8 months.
ALK: The latest result of the first home-grown ALC inhibitor, the ALC gene, is a very important driver of NSCLC, but this mutation occurs less often, accounting for only 3% to 5% of lung cancer, and is therefore also known as the "diamond mutation".
research on APK mutations has progressed rapidly, with targeted drugs emerging that can inhibit tumors with precision and efficiency, and have grown to three generations.
conference, the results of a subgroup analysis of a new generation of APK inhibitors, Nsatini, were studied in eXalt3.
Nsatinib has been approved for market in China for second-line treatment in patients with localized late stage or metastasis NSCLC who have previously progressed after receiving clostrini treatment or who are resistant to kerthionine.
eXalt3 study included 290 ALK-positive NSCLC patients, with a mid-PFS of 25.8 months in the Ensatinib group vs a 12.7-month PFS in the kerptinib group.
new subgroup analysis showed that patients with a history of chemotherapy were more effective at using nsatinie than those without a history of chemotherapy (mPFS NR vs 25.8).
specific target drugs, the conference also reported on the progress of several studies based on different treatments for specific mutations.
In summary, targeted therapy in the field of lung cancer further consolidates its role in selected patients and is emerging in the field of treatment, both as a single drug and as a joint strategy, which will play an irreplaceable role in the field of lung cancer.
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