Japan moved fast to authorize to use lorlatinib, a third-generation targeted therapy, for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), an expert said. In contrast, it is still unclear whether the drug will arrive in the Korean market.

Professor Takashi Seto at Japan’s National Kyushu Cancer Center said Japanese cancer patients already had access to advanced treatment for the disease, compared to Korean cancer patients, in a recent interview with Korea Biomedical Review.

For the treatment of ALK-positive NSCLC, Korea authorized Alecensa (ingredient: alectinib), a second-generation targeted therapy, as the first-line treatment in April last year. It allowed insurance benefits at the end of last year.

Seto said Japan allowed prescription of Alecensa in 2012, six years earlier than Korea.

Seto introduced a massive real-world study in Japan at the Congress of the Korean Academy of Tuberculosis and Respiratory Diseases (KATRD International Conference 2019), in Seoul, Nov. 7-8.

“This study was possible because Japan approved Alecensa as the first-line therapy earlier than other countries,” he said.

The study compared a patient group who used the first-generation targeted therapy Xalkori (ingredient: crizotinib) with another group with second-generation Alecensa for the first-line treatment of ALK-positive NSCLC. The data proved that the sequential treatment using Xalkori and Alecensa was beneficial in Time to Treatment Failure (TTF).

The study analyzed data from patients who were initially treated with Xalkori or Alecensa at 61 institutions in Japan between May 2012 and December 2016.

“Japan recommends three agents for the treatment of ALK-positive NSCLC -- Xalkori, Alecensa, and Zykadia (ingredient: ceritinib). There are no restrictions for permit or reimbursement for sequential treatment,” Seto said.

Even though there is no data, the Japanese treatment guidelines recommend using lorlatinib as the second-line treatment for stage-four ALK-positive NSCLC patients who failed in the first-line Alecensa treatment, he noted. The clinical data of Japan also showed that Japanese doctors prescribed lorlatinib for patients who failed in Alecensa treatment, he added.

Lorlatinib is the third-generation targeted therapy, developed by Pfizer as a follow-up to Xalkori, the first-generation drug. Japan gave the nod for lorlatinib last year, according to the Japanese expert.

“Lorlatinib responds to most patients without the need for analysis or evaluation of resistance mechanisms because the drug itself has extensive anti-cancer activity against mutations,” Seto said. Lorlatinib was developed by the same scientist who created Xalkori and modified Xalkori's structure to improve the efficacy and reduce the toxicity, he added.

In Korea, Pfizer has not even applied for lorlatinib approval. The company obtained conditional approval for the drug in the U.S., Europe, and Japan, based on the results of the phase-2 trials. Pfizer must submit additional data from the post-marketing studies and the results of the CROWN study, which compares lorlatinib with Xalkori in the first-line treatment to the regulatory agencies.

Industry officials expect that Pfizer will be able to seek the lorlatinib permit in Korea after completing the global trials.