Pfizer's Lorviqua wins insurance coverage for 1st-line ALK-positive NSCLC in Korea

Pfizer Korea’s third-generation anaplastic lymphoma kinase (ALK) inhibitor Lorviqua (ingredient: lorlatinib) has received expanded health insurance coverage in Korea as a first-line treatment for ALK-positive metastatic non-small cell lung cancer (NSCLC), potentially transforming the treatment paradigm for this rare but aggressive form of lung cancer.

To mark the milestone, Pfizer Korea held a press conference on Wednesday at the Fairmont Ambassador Seoul, highlighting the clinical significance of the drug and its anticipated impact on patient care.

Lorviqua was first approved in Korea in May 2022 as a first-line therapy for ALK-positive metastatic NSCLC. As of May 1, three years after its initial approval, the drug was included in Korea’s national health insurance program for the first-line setting.

“Lorviqua is a third-generation ALK tyrosine kinase inhibitor (TKI) capable of penetrating the blood-brain barrier (BBB), offering significant efficacy even in patients with brain metastases,” Professor Han Ji-youn of the Center for Lung Cancer at the National Cancer Center said during the press conference. “The drug also targets the G1202R mutation, which frequently emerges in patients previously treated with second-generation ALK TKIs.

About 25 to 30 percent of patients with ALK-positive metastatic NSCLC never receive second-line treatment due to rapid clinical deterioration following disease progression, Han added.

Han stressed that the reimbursement of Lorviqua as a first-line option is a critical step forward in addressing unmet needs and improving access to timely and effective treatment.”

Previously, second-generation ALK inhibitors such as brigatinib and alectinib had set a high bar, with median progression-free survival (PFS) around 35 months and five-year overall survival (OS) rates approaching 60 percent.

However, Lorviqua has now surpassed these benchmarks.

The reimbursement decision was based on the five-year follow-up results from the pivotal phase 3 CROWN trial, which compared Lorviqua to the first-generation ALK inhibitor crizotinib. marketed as Xalkori.

The study enrolled 296 treatment-naïve patients with ALK-positive advanced or metastatic NSCLC.

At five years, 60 percent of patients in the Lorviqua arm were alive without disease progression, compared to only 8 percent in the crizotinib group. Lorviqua reduced the risk of disease progression or death by 81 percent, the longest PFS ever reported in ALK-positive NSCLC to date.

Notably, Lorviqua showed powerful efficacy in preventing brain metastases. At 36 months, 92 percent of patients remained free of intracranial disease progression, regardless of their baseline brain metastasis status.

The objective response rate (ORR) reached 81 percent, outperforming the 63 percent seen with crizotinib.

Lorviqua’s safety profile remained consistent over five years of follow-up, with no new safety signals observed.

Permanent treatment discontinuation due to adverse events was reported in 5 percent of patients in the Lorviqua group and 6 percent in the control group. The most frequently reported adverse events of grade 3 or higher included hypercholesterolemia (21 percent), hypertriglyceridemia (25 percent), and weight gain (23 percent).

These benefits were also consistently observed in Asian subgroups, including Korean patients. In Asian patients, the median PFS for Lorviqua was not reached, while that of crizotinib was 9.2 months.

Lorviqua also reduced the risk of intracranial disease progression or death by 99 percent at five years compared to crizotinib.

“Lorviqua is the only ALK-targeted therapy to demonstrate such durable outcomes with over five years of follow-up,” Han said. “Its efficacy data alone clearly positions it as the dominant first-line treatment, making it unlikely that another therapy will surpass it in the near future.”

The treatment has been endorsed by major global oncology guidelines. The National Comprehensive Cancer Network (NCCN) has recommended Lorviqua as a Category 1 preferred first-line treatment since 2025. Similarly, the American Society of Clinical Oncology (ASCO) in 2024 and the European Society for Medical Oncology (ESMO) in 2023 have each granted it their highest levels of recommendation (Tier I-A).

ALK-positive NSCLC accounts for roughly five percent of all lung cancer cases in Korea, often affecting younger patients with little to no history of smoking. These patients frequently present with brain metastases at diagnosis, making central nervous system (CNS) control a critical treatment goal.

Despite concerns regarding CNS  side effects, such as cognitive and emotional disturbances, observed more frequently with Lorviqua, Han stressed that most cases were manageable, and only two percent of patients discontinued treatment permanently due to CNS-related adverse events.

“While CNS toxicity may initially raise concerns, the overwhelming long-term benefit in controlling both systemic and intracranial disease justifies its frontline use,” Han said. “If necessary, clinicians can monitor patients closely in the early treatment phase and consider switching to second-generation therapies only if intolerable side effects arise.”

Given the durability of disease control, the ability to prevent brain metastases, and its endorsement by international guidelines, Lorviqua should now be considered the standard-of-care first-line treatment for ALK-positive metastatic NSCLC in Korea, she added.