Laura tini's first-line treatment of ALC-NSCLC reduced the risk of disease progress or death by 72%.

ALK fusion is an important therapeutic target for advanced non-small cell lung cancer (NSCLC), known as "diamond mutation".
Since the FDA approved the first generation of ALK-TKI cytocininib, the second generation of ALK-TKI altinib, Ceredigioni, bugtinib and three generations of ALK-TKI Lauratinib have enriched the pattern of sequential drug use, ALK fusion positive patients with a significantly longer total survival period (OS), and gradually entered the "slow disease" management era.
new problems followed, blooming APK inhibitors, the first-line battleground, who is fighting? On the first day of the 2020 ESMO Conference, the Phase III CROWN Crown Study of the Third Generation ALK-TKI Lara Tini-Pyktinib First-Line Treatment of Late ALK-Positive NSCLC was announced, or will bring new thinking, which is the world's most high-profile study after Pfizer announced in August that it had reached the end of its major research period of no progress (PFS).
In 2018, the FDA approved loratinib for treatment with progression-positive ALK-positive metastasis NSCLC after treatment with cytocininib and at least one other ALK inhibitor;
based on excellent tumor objective remission rate and remission duration, the adaptive disorder was approved at an accelerated rate.
CROWN is a validation study that translates into full approval.
Pfizer announced in August that the Lorraine III CROWN study for late-stage ALK-positive NSCLC had reached its main end, and that the drug had been shown to significantly extend the patient's PFS compared to closinib.
safety information is consistent with past clinical trials.
(Source: ESMO 2020, same as 1) 1, Research Design CROWN is a randomized open two-arm parallel PHASE III study conducted in 23 countries, 104 medical centers, including 296 first-time patients with PHASE IIIb/IV ALC-positive NSCLC.
patients who met the group criteria were treated with 1:1 loratinib (100 mg QD) or cloptotinib (250 mg BID) to study stratization on the basis of race and whether there was CNS transfer.
main endpoint is PFS assessed by the Independent Centre for Blind Law Review Committee (BICR).
secondary endpoints include total lifetime, objective mitigation rate (ORR) based on BICR and researcher evaluation, intracranial objective mitigation rate (IC-ORR), reaction duration, intracranial reaction duration (IC-DOR), and progress time to intracranial lesions (IC-TTP), PFS based on researcher evaluation, and safety.
2, the study results data as of March 20, 2020, the middle follow-up time of the La Trotinie group (n=149) and the kertinist group (n=147) was 18.3 months and 14.8 months, respectively.
based on BIRC assessments, Laroteni significantly extended the mid-PFS, which was not reached and 9.3 months, respectively, reducing the risk of disease progressity or death by 72% (HR-0.28%, 95% CI, 0.191-0.413; P<0.001).
PFS assessed by the researchers was not reached and 9.1 months (HR=0.21, 95% CI, 0.144-0.307), respectively.
subgroup analysis showed that Lauratinist's PFS benefited better than cytosini, regardless of brain metastasis, race, ECOG PS score, gender, age, and smoking status.
the end points of the second secondary study, the two ORRs were 76% and 58% (OR, 2.25; 95% CI, 1.35-3.89), respectively. The intracranial objective remission rate in the Laroteni group was as high as 82%, well above the 23% in the clotinist group (OR, 16.83; 95% CI, 1.95-163.23).
, 71% (12 cases) of patients with measurable brain metastasis lesions were treated with Lara tinib to achieve intracranial complete remission (CR), reflecting Lara tinib's amazing ability to enter the brain.
safety analysis showed that the rates of adverse events in the two groups of level 3 and above were 72.5% and 55.6%, respectively, and resulted in 7% and 9% of patients stopping treatment, respectively.
most common level 3-4 adverse events in the Lauratini group were abnormal laboratory test results, including hypercholesterolemia and hyperglycerideemia.
3. Compared with closinib, the first-line treatment of ALK-positive late NSCLC has brought clinical and statistical benefits to PFS, ORR, IC-ORR and should be considered as a new first-line treatment.
4, Live Guest Review Dr. Christine M. Lovly of Vanderburg University Medical Center in the United States gave the study high praise, and The first-line treatment of ALC-positive late NSCLC demonstrated very promising results.
then, Dr. Christine M. Lovly compared the efficacy and safety of second- and third-generation ALK-TKI with kerptinib - is there an "optimal solution" to the first-line treatment of ALK-positive late NSCLC when clinical practice faces multiple options? What other directions are there to explore in the future? She noted that ALK-positive first-line drug selection needs to take into account biological factors including duration of treatment, range of CNS activity, toxicity maps and long-term adverse events.
current data show that La Otinico is effective against all types of ALC secondary drug-resistant gene mutations, and has strong CNS permeability.
ALK gene testing is critical to screening suitable therapeutic populations, and researchers are conducting more ALC-positive NSCLC clinical trials on a broader scale, including first-line combination therapy (e.g., combined immunosuppressants, VEGFR inhibitors, other rare target therapies, chemotherapy, etc.), second-line and above combination therapy, monitoring ALC-TKI efficacy through circulating tumor DNA (ctDNA), and consideration of co-mutations (e.g. TP53).
In addition to ALK-TKI, potential ALK targeted treatments include variant inhibitors, protein degradation target chimosa technology (PROTACS) and cancer vaccines;
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