Start Your Search
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): Y.J. 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.
Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.