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J. Shih
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MINI 17 - WT EGFR, Angiogenesis and OMD (ID 131)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:R. Feld, R. Dziadziuszko
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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MINI17.01 - Maintenance with Gefitinib/Pemetrexed (G/P) or P After Induction P/Platinum for Stage IV Lung Adenocarcinoma with No Sensitizing EGFR Mutation (ID 608)
16:45 - 18:15 | Author(s): J. Shih
- Abstract
- Presentation
Background:
We have proposed that synergistic epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-chemotherapeutic interaction in lung cancer cells has 3 essentials: no platinum, cells not or no more sensitive to EGFR-TKI, and using a synergistic chemo partner, e.g., pemetrexed (P) (Tsai, et al. Lung Cancer 82:305, 2013).
Methods:
GENIUS study (NCT01579630) was a phase II, multicenter, randomized, open-label prospective trial comparing maintenance G/P versus P in patients with metastatic lung adenocarcinoma (mLADC) harboring no sensitizing EGFR mutations (sEGFRm) detected by high sensitivity methods following a 4-cycle P/Platinum induction therapy in frontline setting. Patients with no disease progression (PD) were 1:1 randomized to receive P (500 mg/m[2], 3-week cycle) ± G (250 mg, daily) until PD or treatment failure, and stratified by study site and response. The primary endpoint was progression free survival (PFS) by both independent radiologist review (IRR) and investigator assessment (IA), secondary endpoints included time to treatment failure (TTF), overall survival (OS), safety and toxicity profile.
Results:
Between 03/2011 and 11/2013, 55 patients were randomized, G/P 26, P 29. Baseline characteristics were balanced between arms (age 57; female 42%; never smoker 55%; ECOG1 91%; ≥2 metastatic sites 38.2%; ALK+ 16%). Median follow-up was 20.4 mo. Median cycle of treatment was G/P 9.5 (range 1-32) and P 4 (2-21). Median PFS was substantially longer for G/P than P, both by IRR (3 deemed as PD at randomization were excluded; n = 25 v 27): 8.4 v 3.8 mo; HR [95% CI] 0.42 [0.23-0.79]; p = 0.0057, and by IA: 8.7 v 2.9 mo; HR 0.38 [0.21-0.70], p = 0.0013. Response with induction therapy, age, and smoker had interactions with treatment for PFS. Median TTF: 7.0 v 2.9 mo; HR 0.46 [0.25-0.83], p = 0.0085. OS was also better for G/P than P by IRR (undefined v 29.3 mo; HR 0.44 [0.20-0.97]; p = 0.037) and IA (undefined v 21.7 mo; HR 0.46 [0.22-0.97]; p = 0.038). There were more treatment-related diarrhea, liver and skin toxicities on G/P v P, but generally mild. Two G/P patients were off-study due to liver toxicity.
Conclusion:
This proof of concept ph 2 study first demonstrated survival benefit of EGFR-TKI plus chemo in the maintenance phase of frontline treatment for patients with mLADC harboring no sEGFRm. This strategy deserves phase III study to confirm.
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MINI17.06 - Subgroup Analysis of East Asian Patients in the Phase III REVEL Trial (ID 729)
16:45 - 18:15 | Author(s): J. Shih
- Abstract
- Presentation
Background:
The REVEL trial demonstrated that second-line treatment with ramucirumab (RAM) plus docetaxel (DOC) significantly improved overall survival (OS) compared to placebo (PBO) plus DOC in the intent-to-treat (ITT) population (N=1253) of patients with stage IV non-small cell lung cancer. The REVEL trial also significantly improved progression-free survival (PFS) and objective response rates (ORRs). Results from the East Asia (EA) subgroup (Taiwan and Korea) analysis are presented.
Methods:
Subgroup analyses were performed in the EA ITT population, which consisted of all patients who were randomized in Taiwan (n=27) and Korea (n=62). Endpoints evaluated in the EA subgroup were OS, PFS, ORR, and safety. OS and PFS were analyzed using the Kaplan-Meier method and Cox proportional hazard model. Response was compared using the Cochran-Mantel-Haenszel test. ClinicalTrials.gov number NCT01168973.
Results:
In the 89 ITT EA patients, median OS was 15.44 months for the RAM plus DOC arm (n=43) and 10.17 months for PBO plus DOC arm (n=46) (HR: 0.762, 95% CI: 0.444–1.307). Median PFS was 4.88 months for the RAM plus DOC arm and 2.79 months for the PBO plus DOC arm (HR: 0.658, 95% CI: 0.408–1.060). The ORRs were 25.6% (95% CI: 13.5–41.2) in the RAM plus DOC arm and 9% (95% CI: 2.4–20.8) in the PBO plus DOC arm. Approximately two years after the enrollment of the first patient, in May 2012, the independent data monitoring committee recommended a reduction in the dose of DOC from 75 mg/m[2] to 60 mg/m[2] for newly enrolled EA patients, based on a higher incidence of neutropenia and febrile neutropenia associated with 75 mg/m[2] in EA patients compared to non-EA patients. This amendment resulted in a reduction in the toxicity associated with the original treatment regimen (Table). Table: Select grade ≥3 treatment-emergent adverse events, regardless of causality, by treatment arm and DOC dose in EA patients
Data are n (%). *Consolidated term.Preferred term RAM plus DOC (75 mg/m[2]) (n = 32) PBO plus DOC (75 mg/m[2]) (n = 33) RAM plus DOC (60 mg/m[2]) (n = 11) PBO plus DOC (60 mg/m[2]) (n = 13) Any 31 (96.9) 26 (78.8) 6 (54.5) 7 (53.8) Neutropenia* 26 (81.3) 24 (72.7) 6 (54.5) 5 (38.5) Febrile neutropenia 14 (43.8) 4 (12.1) 0 1 (7.7)
Conclusion:
Although not statistically powered to demonstrate significant improvement, the improved OS, PFS, and ORR observed in the EA subgroup treated with RAM plus DOC is consistent with the treatment effect observed in the overall ITT population in the REVEL trial. A dose reduction in DOC from 75 mg/m[2] to 60 mg/m[2] was associated with an improved safety profile and a reduction in the incidence of febrile neutropenia in the EA subgroup.
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