TAGRISSO (Page 6 of 8)

14.3 Previously Treated EGFR T790M Mutation-Positive Metastatic NSCLC

The efficacy of TAGRISSO was demonstrated in a randomized, multicenter open-label, active-controlled trial in patients with metastatic EGFR T790M mutation-positive NSCLC who had progressed on prior systemic therapy, including an EGFR TKI (AURA3). All patients were required to have EGFR T790M mutation-positive NSCLC identified by the cobas® EGFR Mutation Test performed in a central laboratory prior to randomization.

A total of 419 patients were randomized 2:1 to receive TAGRISSO (n=279) or platinum-based doublet chemotherapy (n=140). Randomization was stratified by ethnicity (Asian vs non-Asian). Patients in the TAGRISSO arm received TAGRISSO 80 mg orally once daily until intolerance to therapy, disease progression, or investigator determination that the patient was no longer benefiting from treatment. Patients in the chemotherapy arm received pemetrexed 500 mg/m2 with carboplatin AUC5 or pemetrexed 500mg/m2 with cisplatin 75 mg/m2 on Day 1 of every 21-day cycle for up to 6 cycles. Patients whose disease had not progressed after four cycles of platinum-based chemotherapy could have received pemetrexed maintenance therapy (pemetrexed 500 mg/m2 on Day 1 of every 21-day cycle).

The major efficacy outcome measure was progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) by investigator assessment. Additional efficacy outcome measures included overall response rate (ORR), duration of response (DoR), and overall survival (OS). Patients randomized to the chemotherapy arm who had radiological progression according to both investigator and blinded independent central review (BICR) were permitted to cross over to receive treatment with TAGRISSO.

The baseline demographic and disease characteristics of the overall trial population were: median age 62 years (range: 20‑90 years), ≥75 years old (15%), female (64%), White (32%), Asian (65%), never smoker (68%), WHO performance status 0 or 1 (100%). Fifty-four percent (54%) of patients had extra-thoracic visceral metastases, including 34% with central nervous system (CNS) metastases (including 11% with measurable CNS metastases) and 23% with liver metastases. Forty-two percent (42%) of patients had metastatic bone disease.

In AURA3, there was a statistically significant improvement in PFS in the patients randomized to TAGRISSO compared to chemotherapy (See Table 11 and Figure 4). No statistically significant difference was observed between the treatment arms at final OS analysis. At the time of the final OS analysis, 99 patients (71%) randomized to chemotherapy had crossed over to TAGRISSO treatment.

Table 11. Efficacy Results According to Investigator Assessment in AURA3
Efficacy Parameter TAGRISSO (N=279) Chemotherapy (N=140)
Without documented radiological disease progression
Stratified by ethnicity (Asian vs non-Asian)
Pike estimator
Stratified log-rank test
Logistic regression analysis

Progression-Free Survival

Number of events (%)

140 (50)

110 (79)

Progressive disease (%)

129 (46)

104 (74)

Death *(%)

11 (4)

6 (4)

Median PFS in months (95% CI)

10.1 (8.3, 12.3)

4.4 (4.2, 5.6)

Hazard Ratio (95% CI)

0.30 (0.23,0.41)

p-value §


Overall Survival

Number of deaths (%)

188 (67)

93 (66)

Median OS in months (95% CI)

26.8 (23.5, 31.5)

22.5 (20.2, 28.8)

Hazard Ratio (95% CI)

0.87 (0.67, 1.12)

p-value §


Overall Response Rate

ORR, % (95% CI)

65 (59, 70)

29 (21, 37)

Complete response, %



Partial response, %



p-value #


Duration of Response (DoR)

Median in months (95% CI)

11.0 (8.6, 12.6)

4.2 (3.0, 5.9)

Figure 4. Kaplan-Meier Curves of PFS by Investigator Assessment in AURA3

(click image for full-size original)

In a supportive analysis of PFS according to blinded independent central review, median PFS was 11 months in the TAGRISSO arm compared to 4.2 months in the chemotherapy arm (HR 0.28; 95% CI: 0.20, 0.38).

Of 419 patients, 205 (49%) had baseline brain scans reviewed by BICR; this included 134 (48%) patients in the TAGRISSO arm and 71 (51%) patients in the chemotherapy arm. Assessment of CNS efficacy by RECIST v1.1 was performed in the subgroup of 46/419 (11%) patients identified by BICR to have measurable CNS lesions on a baseline brain scan. Results are summarized in Table 12.

Table 12. CNS ORR and DoR by BICR in Patients with Measurable CNS Lesions at Baseline in AURA3
According to RECIST v1.1.
Based on confirmed response.
Based on patients with response only; DoR defined as the time from the date of first documented response (complete response or partial response) until progression or death event.





CNS Tumor Response Assessment *

CNS ORR, % (95% CI)

57 (37, 75)

25 (7, 52)

Complete response, %



Duration of CNS Response *

Number of responders



Response Duration ≥ 6 months, %



Response Duration ≥ 9 months, %



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