Author of

• 11692

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  P2.10 - Poster Session 2 - Chemotherapy (ID 207)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11729

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    P2.10-037 - Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after completing at least 4 cycles of pemetrexed plus cisplatin induction treatment: a cross-trial analysis of two phase III trials (ID 2449)

    09:30 - 09:30  |  Author(s): L.G. Paz-Ares
    • Abstract

    Background
    In a phase III trial, JMDB, the subgroup of patients with nonsquamous histology showed a significant improvement in survival after treatment with first-line pemetrexed + cisplatin (pem 500 mg/m[2] + cis 75 mg/m[2] every 21 days for a maximum of 6 cycles). In PARAMOUNT, a double-blind, placebo-controlled, phase III trial, 539 patients with advanced nonsquamous NSCLC and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 were randomized to maintenance pem or placebo after completing 4 cycles of pem+cis without disease progression.

    Methods
    We compared patients from the two randomized arms of PARAMOUNT with a selected homogeneous population from JMDB: 346 patients with advanced nonsquamous NSCLC and an ECOG PS of 0 or 1 who completed at least 4 cycles of pem+cis without disease progression. Efficacy outcomes included overall survival (OS) and progression-free survival (PFS) measured from the start of treatment with pem+cis and analyzed by Kaplan-Meier and Cox methods. Rates of toxicities were calculated without formal statistical comparison.

    Results
    Outcomes for the JMDB homogeneous group were similar to the PARAMOUNT placebo arm (PFS: 6.24 vs 5.59, p=0.117; OS: 14.23 vs 13.96, p=0.979). The PARAMOUNT pem group had statistically superior efficacy compared with the JMDB homogeneous group (PFS: 7.46 vs 6.24 p<0.00001; OS: 16.89 vs 14.23 p=0.003). Patients who received pem maintenance displayed numerically higher incidences of drug-related serious adverse events (SAEs) compared with JMDB patients who received ≥4 cycles of pem+cis (10.6% vs 2.9%); grade 3/4 anemia and fatigue were higher in the pem arm of PARAMOUNT. A comparable number of patients (approximately 2/3) on both arms of PARAMOUNT and on JMDB received post-discontinuation systemic therapy (PDT). Results are summarized in Table 1. Table 1: Summary of survival, post-discontinuation systemic therapy , and selected drug-related adverse events in the PARAMOUNT pem and placebo arms and the JMDB homogeneous group

    	PARAMOUNT pem arm (n=359)	PARAMOUNT placebo arm (n=180)	JMDB homogeneous group (n=346)
    PFS
    Median (95% CI), mos	7.46 (6.90-8.57)	5.59 (5.45-5.95)	6.24 (5.91-6.54)
    Cox unadjusted HR (95% CI)	0.66 (0.56-0.77)*	0.86 (0.72-1.04)**
    Unadjusted log-rank p-value	<0.00001*	0.117**
    OS
    Median (95% CI), mos	16.89 (15.77-18.99)	13.96 (12.88-15.51)	14.23 (12.94-15.05)
    Cox unadjusted HR (95% CI)	0.75 (0.63-0.91)*	1.00 (0.81-1.24)**
    Unadjusted log-rank p-value	0.003*	0.979**
    Received any PDT, n %	231 (64.3)	129 (71.7)	207 (59.8)
    Patients with ≥1 drug-related SAE, n (%)	38 (10.6)	8 (4.4)	10 (2.9)
    Hematologic grade 3/4 toxicities, n (%)
    Anemia Hemoglobin decreased Hemoglobin	16 (4.5) 2 (0.6) 0 (0.0)	2 (1.1) 0 (0.0) 0 (0.0)	0 (0.0) 0 (0.0) 10 (2.9)
    Neutropenia Neutophils/granulocytes	17 (4.7) 0 (0.0)	0 (0.0) 0 (0.0)	0 (0.0) 18 (5.2)
    Nonhematologic grade 3/4 toxicities, n (%)
    Fatigue	11 (3.1)	2 (1.1)	5 (1.4)

    *PARAMOUNT pem arm vs JMDB homogeneous group; **PARAMOUNT placebo arm vs JMDB homogeneous group. Abbreviations: PDT=post-discontinuation systemic therapy; PFS: progression-free survival; OS: overall survival; SAE: serious adverse event

    Conclusion
    The PARAMOUNT placebo arm showed results consistent with the JMDB homogeneous group treated with pem+cis. The addition of pem continuation maintenance treatment results in a statistically significant increase in OS and PFS. Although there was an increase in the incidence of grade 3/4 toxicities with longer exposure to pem+cis or maintenance pem, the overall incidence remains low, underscoring the relative safety of these treatment regimens.