EGFR lung cancer care shifts to combo therapies, but reimbursement gaps limit access in Korea

The treatment approach for EGFR-mutated non-small cell lung cancer (NSCLC) is moving toward the use of more combination therapies. However, Korea’s insurance coverage still primarily focuses on single-drug treatments, prompting calls for greater patient access.

In particular, while both Tagrisso (osimertinib) + pemetrexed + platinum-based chemotherapy and Leclaza (lazertinib) + Rybrevant (amivantamab) are recognized as equivalent standard treatment options in global guidelines, only one therapy is widely reimbursed, creating a clear disparity between the two.

US NCCN designates Leclaza combo as ‘preferred regimen’ following Tagrisso

The combination therapy of lazertinib and amivantamab was recently designated as the preferred regimen for first-line treatment of EGFR-mutated metastatic NSCLC in the U.S. National Comprehensive Cancer Network (NCCN) guidelines.

Previously, the preferred regimens included osimertinib monotherapy or osimertinib plus pemetrexed with platinum-based chemotherapy. Now, the lazertinib and amivantamab combination has been added to the recommendations. This has shifted the first-line treatment paradigm for EGFR-mutated NSCLC toward combination therapy.

“Treatment for EGFR-mutated lung cancer is evolving beyond monotherapy. We are now seeing combination therapy with chemotherapy or dual-specific antibodies,” Professor Ahn Myung-ju of Samsung Medical Center said at the IASLC Asia Conference on Lung Cancer (ACLC 2025) in Ho Chi Minh City, Vietnam, from Oct. 9 to 11. “A new treatment paradigm is emerging, centered on the FLAURA2 and MARIPOSA studies.”

In the FLAURA2 study, osimertinib plus pemetrexed showed improved progression-free survival (PFS) of 25.5 months vs. 16.7 months (hazard ratio [HR] 0.62). Overall survival (OS) was 47.5 months vs. 37.6 months (HR 0.77) compared with monotherapy.

The MARIPOSA study showed that lazertinib plus amivantamab achieved a PFS of 23.7 months and an OS of 36.7 months.

Tagrisso combo gets partial coverage, while Leclaza combo coverage remains limited

Despite both combination therapies being established as standards based on robust clinical evidence, Korea’s reimbursement system treats them differently, covering only one and leaving the other largely excluded.

In May, the Health Insurance Review and Assessment Service (HIRA) expanded partial insurance coverage for combination treatments, now covering Tagrisso in combination with pemetrexed and platinum chemotherapy for EGFR-mutated lung cancer. This improved patient access.

Under this revised system, Tagrisso's coverage is maintained while allowing combination with relatively lower-cost chemotherapy drugs, significantly reducing patients' out-of-pocket expenses.

In contrast, coverage for Leclaza + Rybrevant is much more limited because Rybrevant is not reimbursed. While Leclaza is covered for first- and second-line use, high costs without Rybrevant coverage restrict many patients’ access, unlike the broader support for Tagrisso combinations.

Currently, Rybrevant has only received approval from the Cancer Disease Review Committee (CDRC) for one indication — second-line or later treatment of EGFR exon 20 insertion mutation-positive NSCLC. The MARIPOSA clinical trial indication supporting the Leclaza combination was denied coverage.

This results in a pronounced gap in accessibility: Tagrisso combination therapy is accessible thanks to reimbursement, but Leclaza combination therapy — despite similar global evidence — remains out of reach for many due to lack of coverage.

Rybrevant has been approved by the CDRC for only one of its four indications in Korea. The approved use is for monotherapy as a second-line or later treatment for EGFR exon 20 insertion mutation NSCLC, based on results from the CHRYSALIS study.

Other indications were not approved. These include: first-line combination therapy for EGFR exon 20 insertion mutation (carboplatin + pemetrexed); first-line combination therapy for EGFR exon 19 deletion or L858R mutation (with lazertinib); and second-line combination therapy for the same mutation (carboplatin + pemetrexed).

The main issue is the rejection of uses backed by large phase 3 clinical trials — such as MARIPOSA, MARIPOSA-2, and PAPILLON — even though these trials showed clear survival benefits. Only second-line single-drug use, with less evidence, was approved.

Some critics say the decision prioritized financial impact over clinical utility. Others argue this judgment hinders domestic access to the global standard of Leclaza and Rybrevant combination therapy.

Both combos are standard, but reimbursement leans one way

Experts underscore that although both combination therapies are established first-line standards, only one receives reimbursement, making Korea’s system lopsided.

Both the Tagrisso + pemetrexed combination from FLAURA2 and the Leclaza + Rybrevant combination from MARIPOSA showed survival benefits. However, only the former gained patient access through partial reimbursement. The latter remains effectively non-reimbursed.

Thus, although combination therapies are the new norm, Korea’s uneven reimbursement keeps practical access limited to just one, leaving the other out despite evidence.

Professor Ahn also pointed out at the ACLC 2025 conference: “Osimertinib monotherapy, osimertinib plus chemotherapy, and amivantamab plus lazertinib combination therapy all demonstrate survival benefits. Yet, drug access remains limited in the Asia-Pacific region.”

Yuhan and J&J co-promote Rybrevant; will they improve access?

Yuhan Corp. has partnered with Johnson & Johnson to co-promote the combination therapy of Rybrevant and Leclaza in Korea. Through this agreement, Yuhan has expanded beyond its previous focus on Leclaza alone to co-market the combination therapy.

A Janssen Korea representative said, “Rybrevant received approval in September from the Cancer Disease Review Committee for reimbursement as a monotherapy in adult patients with locally advanced or metastatic NSCLC with an EGFR exon 20 insertion mutation whose disease progressed during or after platinum-based chemotherapy.”

The representative added, “This joint promotion agreement is the result of a strategic partnership between Johnson & Johnson and Yuhan. Our goal is to communicate the therapeutic value of the Rybrevant-Leclaza combination as a first-line treatment for EGFR-mutated NSCLC and to enhance patient access.”

The representative continued, “Johnson & Johnson respects and diligently follows procedures set by insurance authorities. Through ongoing communication with stakeholders, we are making efforts to ensure that Rybrevant's indications — including those with Leclaza — are covered by insurance as soon as possible.”