Improving Response in Lung Cancer With CNS Metastases

Tagrisso (osimertinib) had positive outcomes for patients with T790M-positive non–small cell lung cancer (NSCLC) for central nervous system (CNS) metastases.
BY Wayne Kuznar
PUBLISHED June 12, 2017
According to phase 3 results, Tagrisso (osimertinib) had positive outcomes for patients with T790M-positive non–small cell lung cancer (NSCLC) for central nervous system (CNS) metastases.

Marina Chiara Garassino, M.D., chief of the thoracic oncology unit at the National Cancer Institute of Milan, Italy, presented data from a subset analysis of patients with CNS metastases participating in the AURA3 trial. AURA3 is a randomized, international, open-label trial evaluating Tagrisso in patients with T790M-positive advanced NSCLC who progressed after first-line EGFR-TKI therapy.

“The majority of patients had shrinkage in the brain metastases,” she said. “Despite the small number of patients, you can observe, that in the Tagrisso group, responses are more frequent and deeper compared to chemotherapy.”

In patients with CNS evaluable for response (46 patients), CNS overall response rate (ORR) was 70 percent with Tagrisso compared with 31 percent for patients treated with platinum-based doublet chemotherapy. In the full analysis population (416 patients), CNS progression-free survival (PFS) also favored the Tagrisso group, 11.7 months versus 5.6 months.
 
Median time to response was 6.1 weeks in both treatment groups, but overall duration was significantly greater in the Tagrisso group, 8.9 months versus 5.7 months. Disease control rate was 93 percent in the experimental group compared with 63 percent in the control group.

CNS metastases are common in patients with EGFR-positive NSCLC—Garasinno said up to 40 percent of patients will develop such metastases over the course of their disease. She added that prognosis is poor for these patients, with a median PFS of three months to six months.

In AURA 3, patients were assigned to 80 mg of oral Tagrisso daily or platinum-pemetrexed chemotherapy every 21 days for up to six cycles. In the group of patients with at least one measurable CNS metastasis, termed the CNS evaluable for response set (cEFR), 30 patients received Tagrisso and 16 received chemotherapy.

In what Garassino called the CNS full analysis set (cFAS), 75 patients were assigned to the experimental group and 41 were assigned to chemotherapy. Data cutoff was April 15, 2016.

In the cFAS group, CNS ORR was 40 percent with Tagrisso and 17 percent with chemotherapy.

Among patients in the cFAS population who had radiotherapy to the brain within six months of entering the trial, CNS ORR was 64 percent for patients assigned to Tagrisso (14 patients) compared with 22 percent for patients assigned to chemotherapy (nine patients).

For cFAS patients who did not have radiotherapy or had radiotherapy six months or more months before enrollment, CNS ORR was 34 percent for patients assigned to Tagrisso (61 patients) versus 16 percent for those assigned to chemotherapy (32 patients).

“If we overlap the curves of patients with CNS metastases, you can observe that for chemotherapy, patients with brain metastases fair worse, as expected,” Garassino said. “But you can observe that the curves of patients with brain metastases treated with osimertinib are very similar to those without brain metastases, suggesting that Tagrisso is able to convert the prognosis of patients with brain metastases to similar to patients without brain metastases.”

In 2015, the FDA granted Tagrisso an accelerated approval in this patient population based on data from 411 patients in two single-arm studies.

In the first study, AURA2, ORR was 61 percent for patients with pretreated EGFR T790M-mutant NSCLC assigned to Tagrisso (210 patients). In the second trial, an extension to the AURA study, ORR was 57 percent in 201 patients. In a pooled-analysis of the two studies, the ORR with Tagrisso was 59 percent and duration of response was 12.4-months.

In February 2016, the European Commission (EC) granted a conditional marketing authorization to Tagrisso for patients regardless of prior treatment with EGFR TKI.
 
 
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