Author of

• 10801

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  P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10822

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    P1.11-021 - First-line erlotinib versus cisplatin/gemcitabine (GP) in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC): interim analyses from the phase 3, open-label, ENSURE study (ID 1849)

    09:30 - 09:30  |  Author(s): G. Ladrera
    • Abstract

    Background
    Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor, has proven efficacy in second-/third-line advanced NSCLC, and provides superior first-line efficacy to chemotherapy for patients whose tumors harbor activating EGFR mutations. The phase 3, randomized, open-label ENSURE study evaluated erlotinib vs GP in patients from China, Malaysia and the Philippines with EGFR mutation-positive NSCLC.

    Methods
    Patients ≥18 years with histologically or cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and an ECOG PS of 0–2 were randomized 1:1 to receive either erlotinib (oral; 150mg qd until progression/unacceptable toxicity) or GP (G 1250mg/m[2] iv d1 & 8 q3w; P 75mg/m[2] iv d1 q3w for up to 4 cycles). Patients were stratified by EGFR mutation type, PS, gender, and country). Primary endpoint is progression-free survival (PFS) by investigator, with Independent Review Committee (IRC) assessment for sensitivity analysis; other endpoints include objective response rate (ORR), overall survival (OS), and safety. A pre-planned interim analysis was conducted after 73% of PFS events (cut-off 20 July 2012). An additional exploratory updated analysis (cut-off of 19 November 2012), included all planned PFS events.

    Results
    In total, 217 patients were randomized: 110 to erlotinib and 107 to GP. Baseline characteristics were similar in both groups. Efficacy data by treatment arm for the interim and updated analyses are presented (Table 1). PFS by investigator in EGFR exon 19 deletion and exon 21 L858R mutation subgroups is also presented (Table 1). Erlotinib was better tolerated than GP, with treatment-related serious adverse events (SAEs) occurring in 2.7% vs 10.6% of patients, respectively. The most common grade ≥3 AEs of any cause were neutropenia (25.0%), leukopenia (14.4%) and anemia (12.5%) in the GP arm, and rash in the erlotinib arm (6.4%). At the updated analysis (19 November 2012), erlotinib remained better tolerated than GP, with treatment-related SAEs occurring in 3.6% vs 11.5% of patients, respectively. Median duration of follow-up was 10.3 months and 11.7 months for the GP and erlotinib arms, respectively, at latest cut-off. OS data are not yet mature.

    Efficacy Outcome		Interim analysis (cut-off 20 July 2012)		Updated analysis (cut-off 19 November 2012)
    		E	GP	E	GP
    Investigator-assessed PFS	Events, n	35	66	61	87
    	Median, months	11.0	5.5	11.0	5.5
    	HR (95% CI)	0.34 (0.22–0.51)		0.33 (0.23–0.47)
    	log-rank p-value	<0.0001		<0.0001
    IRC-assessed PFS	Events, n	33	47	51	55
    	Median, months	11.0	5.6	11.1	5.7
    	HR (95% CI)	0.42 (0.27–0.66)		0.43 (0.29–0.64)
    	log-rank p-value	0.0001		<0.0001
    ORR	%	62.7	33.6	68.2	39.3
    	p-value	0.0001		<0.0001
    Disease control rate (DCR)	%	89.1	76.6	91.8	82.2
    	p-value	0.015		0.0354
    EGFR exon 19 deletion subgroup PFS	Median, months	11.1	4.2	11.1	4.3
    	HR (95% CI)	0.20 (0.11–0.37)		0.20 (0.12–0.33)
    EGFR exon 21 L858R subgroup PFS	Median, months	8.3	7.1	8.3	5.8
    	HR (95% CI)	0.57 (0.31–1.05)		0.54 (0.32–0.90)

    p-value significance level: alpha=0.05

    Conclusion
    These analyses demonstrate that erlotinib provides statistically significant and clinically meaningful improvement in both investigator-assessed and IRC-assessed PFS compared with GP in Asian patients with EGFR mutation-positive NSCLC. Primary efficacy results were also supported by secondary endpoints including ORR and DCR.