Professor Zhou Qing: Precise and powerful, long-lasting brain control, loratinib first-line treatment of Asian patients data is remarkable!

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Big coffee shared the results of Crown's study on Asian populations, looking forward to the application prospects of loratinib in ALK-positive NSCLC patients

In recent years, with the in-depth understanding of the molecular characteristics of non-small cell lung cancer (NSCLC), advanced NSCLC is gradually entering the era

The CROWN study showed that loratinib was superior to clezotinib in untreated ALK-positive patients, and the findings supported the use of loratinib for first-line treatment in ALK-positive NSCLC patients with or without baseline brain ^{metastases[2].}

Strong representation——

The CROWN study analyzed data from the Asian population

The CROWN study was an international, ongoing, randomized, Phase III study in

Highly consistent -

The results of the Loratinian population are similar to those of the global population, ushering in the "3+X" era

Professor Zhou Qing said that the efficacy of loratinib in the Asian population and the global population is basically the same, which is reflected in progression-free survival (PFS), objective response rate (ORR) and anti-brain metastases

▎Loratinib has an HR of as low as 0.

In the Asian population, as of September 20, 2021, the median PFS assessed by the Blind Independent Center Assessment (BICR) in the Loratinib and Crizotinib groups were not reached (NR) and 11.
1 months, respectively, and the risk of disease progression or death was significantly reduced by 60% in patients in the loratinib group and 61% and 25% in the two groups at 3 years ^[3].


The median PFS assessed by the investigators was NR and 9.
2 months, respectively, and the risk of disease progression or death was significantly reduced by 76 percent in the loratinib group, and the three-year PFS rates were 63 percent and 12 percent, respectively ^[3].

Figure 1.
A is the median PFS assessed by BICR and B is the median PFS assessed by the investigators

In the global population, PFS follow-up for loratinib and clozotinib lasted 36.
7 months and 29.
3 months as of 20 September
2021.

At this point, although the median PFS in the loratinib group had not yet been achieved, it was significantly longer than that in the crizotinib group, and the median PFS assessed by BICR in both groups was NR and 9.
3 months, respectively; compared with the crizotinib group, the risk of disease progression or death in the loratinib group was significantly reduced by 73%, and the 3-year PFS rates in the loratinib group and the crizotinib group were 63.
5 percent and 18.
9 percent, respectively^[2].

▎The ORR of the Asian population and the global population is 77%-78%:

In the Asian population, 80 percent of patients in the loratinib group and 29 percent of patients in the crizotinib group had a sustained response ≥ 12 months after BICR assessment ^[3
].

The ORRs of the loratinib and crizotinib groups were 78% and 57%, respectively^[3].


In the global population, the ORRs of the loratinib and crizotinib groups were 77.
2 percent and 58.
5 percent, respectively^[2].

▎The intracranial CR rate of the Asian population and the global population is 72%-73%:

In the Asian population, the time to intracranial (IC) disease progression (TTP) in the Loratinib and crizotinib groups was NR and 16.
6 months, respectively, the risk of intracranial progression was significantly reduced by 97%, and the 3-year intracranial no-progression rate was 98% and 42% in both groups ^[3].


Ic-ORRs in the loratinib and crizotinib groups were 73 percent and 20 percent, respectively, for patients with baseline brain metastases, with a complete intracranial response (CR) rate of 73 percent in the loratinib group ^[3].

Figure 2.
BICR-evaluated IC-TTP

In the global population, the three-year intracranial progression rate of loratinib was 72.
8% for patients with baseline brain metastases, and the intracranial CR rate was 72.
2% for first-line treatment, reducing the risk of intracranial progression by 90%^[2].

Safe and reliable——

Adverse reactions are controllable and manageable

Drug safety has always been one of the focal points of clinical concern, Chinese there may be certain differences in pharmacokinetics between east Asian and other races
.

The drug safety data of loratinib in the Asian population have guiding significance
for clinical use in China.

Professor Zhou Qing stressed that the overall incidence of adverse reactions, the incidence of grade ≥ 3 adverse reactions and the toxicity spectrum of loratinib in the Asian population are highly consistent
with the data observed in the global population.

Common adverse events, including hyperlipidemia, edema, weight gain, and central nervous system (CNS) adverse events, are mostly grade 1/2 and are manageable and manageable ^[2,3].


Recently, under the leadership of Professor Wu Yilong, experts in interdisciplinary fields have jointly formulated and issued the "Chinese Expert Consensus on the Management of Loratinib's Special Adverse Reactions^"[4], which states that hyperlipidemia can generally be treated with statin lipid-lowering drugs; Edema can be managed by exercise, salt restriction, compression socks, elevation of the lower extremities, etc.
, and can also be treated with drugs such as diuretics; Weight gain allows for timely dietary adjustments and appropriate physical activity; The vast majority of CNS adverse events can be cured or significantly relieved
with dose adjustment or without clinical intervention.

It's significant —

Loratinib is expected to become the preferred drug for the first-line treatment of ALK in China

The results of the CROWN study confirm that first-line treatment with loratinib has a clear therapeutic benefit compared with clozotinib in both global and Asian populations ^[2,3].


Overall, loratinib is currently the only ALK-TKI with a 3-year PFS rate of more than 60%, the only ALK-TKI that currently has a more than 70% reduction in the risk of disease progression or death in the entire population (total ITT population, baseline and non-transit population), and the only ALK-TKI that currently reduces the risk of intracranial progression in ALK-positive patients by more than 90%^[2
].

At present, ALK-TKI "three generations in the same room", how to do the best platoon deployment, the PFS benefit into the OS benefit, is the future clinical need to pay attention to the problem
.

Professor Zhou Qing said that with the approval of loratinib in China, the three generations of ALK-TKI have become a medical weapon
within reach.

Loratinib can also achieve significant efficacy in the Asian population, and domestic doctors will be more confident to take first-line treatment
with loratinib.

In the future, a new pattern of first-line treatment of ALK-positive NSCLC in China will be opened, and loratinib is expected to become the preferred drug
for first-line treatment of ALK-positive advanced NSCLC in China.

References:

[1] HAO Shuai,HE Yong.
Whole-process management of lung cancer patients with ALK fusion gene positive[J].
Chongqing Medical Science,2017,46(22):3025-3027,3032.

[2] Benjamin J.
Solomon, et al.
Updated Efficacy and Safety From the Phase 3 CROWN Study of First-Line Lorlatinib vs Crizotinib in Advanced Anaplastic Lymphoma Kinase (ALK)–Positive Non-Small Cell Lung Cancer (NSCLC).
AACR2022, Abstract #CT223.

[3] Qing Zhou, Hye Ryun Kim, Ross Soo, et al.
Updated analyses from the CROWN study of first-line lorlatinib vs crizotinib in Asian patients with ALK-positive non-small cell lung cancer.
ESMO2022.
Poster 992P.

[4] Qing Zhou, Shun Lu, Yong Li, Fujun Jia, Guanjun Li, Zhen Hong, U Lu, Yun Fan, Jianying Zhou, Zhe Liu, Juan Li, Yilong Wu, China Thoracic Tumor Research Collaborative Group, Chinese Expert Consensus Working Group on Management of Loratinib Special Adverse Reactions.
Chinese expert consensus on the management of loratinib special adverse reactions[J].
Chinese Journal of Lung Cancer,2022,25(8):555-566.