AstraZeneca’s Tagrisso has become strong enough in early EGFR-mutated lung cancer that Korean doctors say they may have to discuss it after surgery even when patients face the cost without national reimbursement.
The drug, first approved in Korea in 2016 for previously treated EGFR T790M-positive non-small cell lung cancer (NSCLC), has moved far beyond late-stage rescue therapy.
It is now used as first-line treatment, in combination with chemotherapy, as postoperative adjuvant therapy to reduce recurrence after surgery, and as maintenance therapy after concurrent chemoradiotherapy (CCRT) in patients with unresectable stage 3 disease.
That expansion has given AstraZeneca one of the broadest positions in lung cancer. It has also moved the drug into settings where the burden of proof is higher, the patients may still hope to be cured and the cost of delaying access is harder to defend.
Professor Lee Se-hoon of Samsung Medical Center discusses how Tagrisso changed treatment for EGFR-mutated lung cancer patients in Korea over the past decade. (Courtesy of AstraZeneca Korea)
“Explaining non-reimbursed treatment is one of the most painful situations for me,” Lee Se-hoon, professor of hematology-oncology at Samsung Medical Center (SMC), said Tuesday at a press conference marking Tagrisso’s 10th year in Korea. “There is clearly a benefit, but when I have to tell patients that they need to make a choice, I really watch how the eyes of their family members move.”
“One family has to take responsibility for that illness,” he said. “They have to somehow maximize whatever financial resources they have.”
Tagrisso, or osimertinib, has accumulated data across AURA3, FLAURA, FLAURA2, ADAURA and LAURA, trials that have pushed the third-generation EGFR-TKI into nearly every major stage of EGFR-mutated NSCLC.
In ADAURA, the phase 3 trial testing Tagrisso as postoperative adjuvant therapy, Lee said the disease-free survival (DFS) hazard ratio of 0.17 was so striking that doctors initially questioned whether the curve was real.
The later overall survival (OS) benefit, he said, removed most of the remaining debate over the drug’s role after surgery.
“If we do not mention it, or if we fail to bring it up, we could even face legal problems,” Lee said. “It is now an option we must discuss.”
That is a difficult position for Korea’s reimbursement system. The adjuvant use is approved but not reimbursed. AstraZeneca Korea said expanding reimbursement is one of its highest-priority tasks, but gave no timeline.
The company has reason to press the case. Korea has a large EGFR-mutated lung cancer population, and Lee said EGFR-mutated patients can account for 60 to 70 percent of lung cancer patients in his outpatient clinic, partly because they are living longer and staying in care.
Korea also finds more early-stage lung cancers than some Western systems because CT access is relatively high, putting more patients in the adjuvant setting where Tagrisso is approved but still not reimbursed.
The commercial stakes are widening in advanced disease as well. FLAURA2 showed Tagrisso plus platinum-based chemotherapy reached a median OS of 47.5 months, close to four years. The result has moved the field beyond the old question of whether Tagrisso alone can beat earlier EGFR-TKIs.
Lee said first-line EGFR treatment is now becoming a more difficult conversation with patients because doctors must weigh monotherapy against combination therapy, brain metastasis risk, disease burden, tolerability and cost. A single factor is not enough to define high risk, he said.
The combination also changes how doctors think about the brain. EGFR-mutated lung cancer often spreads to the central nervous system (CNS), and Lee said Tagrisso’s brain activity was one of the clearest changes he felt in practice.
Before Tagrisso, he said, doctors sometimes increased doses of older drugs off label to try to reach brain disease.
With Tagrisso-based combinations, he said, CNS responses appear deeper, which could matter in Korean hospitals where brain MRI appointments can take months.
“At large hospitals, brain MRI appointments are not available within four months because there are so many cancer patients,” Lee said. “If we can avoid doing surveillance MRIs as often, that is also a meaningful convenience for patients.”
Lee Ji-yun, AstraZeneca Korea’s oncology medical head, discusses AstraZeneca’s lung cancer strategy after a decade in which Tagrisso reshaped treatment for EGFR-mutated NSCLC in Korea. (Courtesy of AstraZeneca Korea)
AstraZeneca is also working past Tagrisso’s next limit: resistance. Lee Ji-yun, AstraZeneca Korea’s oncology medical head, said the company is studying combinations that keep Tagrisso as a backbone after progression while adding MET-targeted therapies or antibody-drug conjugates.
The same logic is pushing more repeat testing. Professor Lee of SMC said that 10 years ago he rarely told patients they needed another biopsy. Now, repeated tissue biopsy or cell-free DNA testing has become part of advanced EGFR lung cancer care.
“When I start treatment now, I may explain what is available today,” Professor Lee said. “But over the next three or four years, there will likely be more things I can offer.”
Kim Ji-hye
댓글
0