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ORAL 32 - EGFR WT and MT Targeting (ID 144)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:K.J. O'Byrne, D.R. Gandara
- Coordinates: 9/09/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
ORAL32.07 - Randomized Phase II Trial of Sequential Gefitinib and Pemetrexed/Cisplatin Chemotherapy for Stage IIIB/IV Lung Adenocarcinoma in Never Smokers (ID 1332)
16:45 - 18:15 | Author(s): G.K. Lee
While concurrent administration of EGFR-TKI and chemotherapy failed to improve the survival outcome, preclinical and clinical data suggested that sequential administration of EGFR-TKI within a chemotherapy cycle might improve the clinical outcome by avoiding the putative antagonism of TKI-induced G1 arrest of the cell cycle phase-dependent activity of chemotherapy. This study was designed to evaluate this idea with gefitinib and Pemetrexed/Cisplatin (Pem/Cis), the best known regimen for lung adenocarcinoma (ADC), in never-smokers with chemo-naive ADC of the lung.
Eligible patients (pts) were never-smokers with chemo-naive stage IIIB/IV ADC, performance status of 0-2 and adequate organ functions, who were randomized after stratification by the EGFR mutation status (positive vs. negative/unknown) to receive either gefitinib (G) 250 mg/day or placebo (P) on days 5-18 of a 3-weekly cycle of chemotherapy, which consisted of Pem 500 mg/m and cisplatin(Cis) 75mg/m given iv on day 1, every 3 weeks for a maximum of 9 cycles. Responding patients continued to receive either G or P every day until PD or unacceptable toxicity. After documentation of PD, pts who had been on P arm were crossed over to receive G. The primary endpoint was progression-free survival (PFS).
Between 06/2012 and 12/2014, 76 pts (M/F: 9/67) with median age of 58.0 years (range 32-75) were enrolled; 72 pts had stage IV and 4 had IIIB tumors. EGFR mutation was (+) in 29, (-) in 43, and unknown in 4. As of 03/17/2015, while randomization code is not broken yet, 53 pts are off treatment (48 due to PD, 2 deaths, 2 patient’s refusal, and 1 due to intercurrent brain tumor) and 19 pts are known dead (17 due to PD and 2 due to other causes). Overall, more pts with EGFR mt(+) tumor received 6 cycles of therapy than those with EGFR mt(-) tumor [28/29 (97%) vs. 32/43 (73%)] and completed 9 cycles of therapy as planned [19/29 (66%) vs. 14/43 (33%)]. The treatment was well tolerated with less G-associated skin toxicities, due to intermittent administration schedule of G per protocol. The most common G3/4 adverse events were: anemia (17.1%), neutropenia (15.8%), vomiting (5.3%), thrombocytopenia (3.9%), and peripheral neuropathy (3.9%). There was no unexpected safety issue except for more Cis-associated peripheral neuropathy which became more noticeable as the treatment continued beyond 6 cycles of therapy. Median PFS was 8.2 months (mos) for the entire group, and 10.6 mos and 6.6 mos for EGFR mt(+) and mt(-) groups, respectively. Overall median survival has not been reached yet with an estimated 2-year survival rate of 56.3%.
First-line sequential administration of G with Pem/Cis chemotherapy was well tolerated with no undue side effects or any compromise in efficacy parameters. Detailed data will be presented to see whether this strategy warrants further investigation in a certain subset of pts with advanced NSCLC.
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