Tagrisso-Chemo Combo Reduces Progression Risk in EGFR-Positive NSCLC With Central Nervous System Metastases

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) treated with Tagrisso (osimertinib) plus chemotherapy experienced a reduction in their risk for central nervous system (CNS) progression, recent study findings demonstrated.

Ultimately, patients who received Tagrisso with chemotherapy had an estimated 9% risk of developing a central nervous system lesion at 24 months, whereas those who received Tagrisso alone had an estimated 23% risk, according to findings from the phase 3 FLAURA2 trial presented at the 2023 European Society for Medical Oncology Congress.

Also, compared with Tagrisso alone, adding chemotherapy to the EGFR tyrosine kinase inhibitor contributed to a higher central nervous system objective response rate (ORR; the percentage of patients who had a partial or complete response to treatment) and better complete response (CR; the disappearance of all signs of cancer as a result of treatment) rate with durable responses, all with a tolerable and manageable safety profile.

“These data support the addition of platinum-pemetrexed to (Tagrisso) as a new firstline treatment option for patients with an EGFR mutated, advanced non-small cell lung cancer, including those with brain (metastases),” Dr. David Planchard, thoracic oncologist and head of the thoracic pathology committee at Institut Gustave Roussy in Paris, France, said during the presentation of the findings.

Prior reports have demonstrated that firstline Tagrisso plus chemotherapy significantly improved progression-free survival (PFS; the time during and after treatment when a patient with cancer lives with the disease without worsening) over Tagrisso alone—this was consistent across all subgroups, including those with brain metastases.

In the FLAURA2 trial, researchers enrolled patients with EGFR-mutated, advanced NSCLC who had not undergone previous treatments. Of note, the trial also permitted patients who had asymptomatic central nervous system metastases that either did not require steroids or were stable for at least two weeks after receiving definitive treatment or steroids.

A total of 557 patients were randomly assigned to receive either firstline Tagrisso with chemotherapy (279 patients) or frontline Tagrisso alone (278 patients). Both groups received the assigned treatment until progression or treatment discontinuation.

Brain imaging was performed on all patients at baseline. It was also performed if, and when, disease progression occurred, although patients with central nervous system metastases at baseline underwent additional-to-scheduled assessments until progression.

Central nervous system-related endpoints were assessed and included ORR, PFS, and duration of response (DOR; the time from when a patient first responds to treatment until disease progression or death). Safety was assessed in both groups.

Researchers performed two analysis sets. The first was a central nervous system full analysis set and included patients with one or more measurable or non-measurable lesions; this set included 118 patients receiving Tagrisso plus chemotherapy and 104 patients receiving Tagrisso alone. The second set was a central nervous system evaluable for response set, which included patients with one or more measurable lesions; this set included 40 patients receiving Tagrisso plus chemotherapy and 38 patients receiving Tagrisso alone.

Findings From the Full Analysis (Measurable and Non-Measurable Lesions)

In the central nervous system full analysis set, the ORR was 73% in the Tagrisso plus chemotherapy group and 69% in the Tagrisso monotherapy group. Of note, 59% (70 patients) of patients assigned Tagrisso plus chemotherapy achieved a CR to therapy compared with 43% (45 patients) of those assigned monotherapy.

The median central nervous system DOR in this analysis was not reached (NR) in the Tagrisso plus chemotherapy group compared with 26.2 months in the Tagrisso only group.

Ultimately, the addition of chemotherapy reduced the risk of central nervous system-related disease progression or death by 42% in this population. At 12 months, the rates of PFS were 87% versus 83% between the combination and monotherapy groups, respectively. At 24 months, the rates were 74% versus 54%.

Results Among Those With Measurable Lesions

For the central nervous system evaluable for response set, the CNS ORR was 88% among patients assigned Tagrisso plus chemotherapy and 87% among patients receiving Tagrisso monotherapy. Complete responses were achieved by 48% (19 patients) versus 16% (40 patients) of patients, respectively.

The median central nervous system DOR in this set was not reached in the Tagrisso plus chemotherapy group and 20.9 months in the Tagrisso alone group.

In this population, the addition of chemotherapy reduced the risk of progression or death by 60%. At 12 months, the PFS rates were 89% versus 73%. At 24 months, the rates were 65% versus 37%.

Safety Analysis

According to Planchard, the safety profiles were consistent with what investigators had expected.

Of note, more severe or worse side effects were reported in the dual therapy arm. Blood-related toxicities were the most reported. Regarding interstitial lung disease (scarring of the lungs), nine patients (3%) and 10 patients (4%) reported this event in the combination and monotherapy groups. Toxicities were most frequent and severe during the induction period and were reported to gradually recede over time.

“(Tagrisso) has proven ability to cross the blood-brain barrier and improve outcomes for patients with lung cancer and (central nervous system) metastases, who often face a poorer prognosis than patients whose disease has not spread to the brain,” said in a press release from AstraZeneca, the manufacturer of (Tagrisso). “In FLAURA2, the addition of chemotherapy to (Tagrisso) led to a complete response and the disappearance of these tumors in the brain in more than half of these patients.”

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