TAGRISSO 80 mg

cified PFS subgroup based on CNS metastases status (identified by CNS lesion site at

baseline, medical history, and/or prior surgery, and/or prior radiotherapy to CNS metastases) at study

entry was performed in FLAURA and is shown in Figure 8. Irrespective of CNS lesion status at study

entry, patients in the TAGRISSO arm demonstrated an efficacy benefit over those in the EGFR TKI

comparator arm and there were fewer patients with new CNS lesions in the TAGRISSO arm compared

to the EGFR TKI comparator arm (TAGRISSO, 11/279 [3.9%] compared to EGFR TKI comparator,

34/277 [12.3%]). In the subset of patients without CNS lesions at baseline, there were a lower number

of new CNS lesions in the TAGRISSO arm compared to the EGFR TKI comparator arm (7/226

Figure 8. Overall PFS by investigator assessment by CNS metastases status at study entry,

Kaplan-Meier plot (full analysis set) in FLAURA

u Hazard Ratio = 0.46 Hazard Ratio = 0.47

e 95% CI (0.36, 0.59) 95% CI (0.30, 0.74)

o r 1. CNS Metastases at Entry = No: TAGRISSO

2. CNS Metastases at Entry = No: SoC

3. CNS Metastases at Entry = Yes: TAGRISSO

4. CNS Metastases at Entry = Yes: SoC

The values at the base of the figure indicate number of subjects at risk.

Patient-reported symptoms and HRQL were electronically collected using the EORTC QLQ-C30 and

its lung cancer module (EORTC QLQ-LC13). The LC13 was initially administered once a week for

the first 6 weeks, then every 3 weeks before and after progression. The C30 was assessed every 6

weeks before and after progression. At baseline, no differences in patient reported symptoms, function

or HRQL were observed between TAGRISSO and EGFR TKI comparator (gefitinib or erlotinib)

arms. Compliance over the first 9 months was generally high (≥70%) and similar in both arms.

Data collected from baseline up to month 9 showed similar improvements in TAGRISSO and EGFR

TKI comparator groups for the five pre-specified primary PRO symptoms (cough, dyspnoea, chest

pain, fatigue, and appetite loss) with improvement in cough reaching the established clinically relevant

cut-off. Up to month 9 there were no clinically meaningful differences in patient-reported symptoms

between TAGRISSO and EGFR TKI comparator groups (as assessed by a difference of ≥10 points).

HRQL and physical functioning improvement analysis

Both groups reported similar improvements in most functioning domains and global health

status/HRQL, indicating that patients’ overall health status improved. Up to month 9, there were no

clinically meaningful differences between the TAGRISSO and EGFR TKI comparator groups in

The efficacy and safety of TAGRISSO in combination with pemetrexed and platinum-based

chemotherapy for the treatment of patients with EGFR mutation-positive locally advanced or

metastatic NSCLC, who had not received previous systemic treatment for advanced disease, was

demonstrated in a randomised, open-label, active-controlled study (FLAURA2). Patient tumour tissue

samples were required to have one of the two common EGFR mutations known to be associated with

EGFR TKI sensitivity (Ex19del or L858R), as identified by local or central testing.

Patients were randomised (1:1) to one of the following treatment arms:

• TAGRISSO (80 mg) orally once daily with pemetrexed (500 mg/m2) and the investigator’s choice

of cisplatin (75 mg/m2) or carboplatin (AUC5) administered intravenously on Day 1 of every 21-

day cycle for 4 cycles, followed by TAGRISSO (80 mg) orally once daily and pemetrexed

(500 mg/m2) administered intravenously every 3 weeks (n=279)

• TAGRISSO (80 mg) orally once daily (n=278)

Randomisation was stratified by race (Chinese/Asian, non-Chinese/Asian or non-Asian), WHO

performance status (0 or 1), and method for tissue testing (central or local). Patients received study

therapy until intolerance to therapy, or the investigator determined that the patient was no longer

The primary efficacy endpoint was PFS as assessed by investigator per RECIST 1.1 and the key

The baseline demographic and disease characteristics of the overall study population were: median age

61 years (range 26-85 years), ≥75 years old (8%), female (61%), Asian (64%), White (28%), never

smokers (66%). Baseline WHO performance status was 0 (37%) or 1 (63%); 98.7% had

predominantly adenocarcinoma histology. Of the patients who had metastatic disease, 49% had

metastatic bone disease, 53% had extra-thoracic metastases and 20% had liver metastases. Forty-one

percent (41%) of patients had CNS metastases (identified by investigator based on CNS lesion site at

baseline, medical history, and/or prior surgery, and/or prior radiotherapy to CNS metastases). With

regard to tumour EGFR mutation type at randomisation, 60.5% were exon 19 deletions and 38.2%

were exon 21 L858R; 0.7% of patients had tumours with both exon 19 deletions and exon 21 L858R.

TAGRISSO in combination with pemetrexed and platinum-based chemotherapy demonstrated a

statistically significant improvement in PFS compared to TAGRISSO monotherapy. The PFS benefit

was consistent across all subgroups analysed. At the time of the second interim analysis of OS (DCO

08 January 2024), statistical significance was not reached.

Efficacy results from FLAURA2 by investigator assessment are summarised in Table 7, the

Kaplan-Meier curve for PFS is shown in Figure 9 and the Kaplan-Meier curve for OS is shown in

Table 7. Efficacy results from FLAURA2 by investigator assessment

Median PFS, months (95% CI)a 25.5 (24.7, NC) 16.7 (14.1, 21.3)

HR (95% CI); P-value 0.62 (0.49, 0.79); P<0.0001

Median OS, months (95% CI) NC (38.0, NC) 36.7 (33.2, NC)

HR (95% CI); P-value 0.75 (0.57, 0.97); P=0.0280b

HR=Hazard Ratio; CI=Confidence Interval, NC=Not Calculable

PFS based on RECIST investigator assessment.

Median follow-up time for PFS in all patients was 19.5 months in the TAGRISSO with pemetrexed and platinum-based

chemotherapy arm and 16.5 months in the TAGRISSO monotherapy arm.

PFS results are from DCO 03 April 2023 (51% maturity). OS results are from DCO 08 January 2024 (41% maturity).

a PFS results by BICR were consistent with those reported via investigator assessment.

b Based on the second interim analysis (41% maturity) a p-value <0.000001 was required to achieve statistical significance.

Figure 9. Kaplan-Meier curves of progression-free survival as assessed by investigator in

Chemo = Pemetrexed and platinum-based chemotherapy.

The values at the base of the figure indicate number of patients at risk.

Figure 10. Kaplan-Meier Curves of Overall Survival in FLAURA2

Chemo = Pemetrexed and platinum-based chemotherapy.