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C. Huang
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-024 - An ENSURE Extension Study to Evaluate 2<sup>nd</sup> Line Erlotinib and Gemcitabine/Cisplatin Cross-Over Treatment for EGFR-Mutant Chinese NSCLC Patients (ID 1747)
09:30 - 09:30 | Author(s): C. Huang
- Abstract
Background:
ENSURE study shows that 1[st] line treatment with erlotinib provides longer PFS over gemcitabine/cisplatin (GP) for stage IIIB/IV NSCLC patients with EGFR mutations. Cross-over treatments after progression of disease (PD) was allowed in ENSURE study. However, post-study treatments might have significant impact on patient survival or other clinical benefits, which is insufficiently investigated. This trial in an extension of the ENSURE study, intended to evaluate PFS in 2[nd] line progression after cross-over treatments in ENSURE.
Methods:
Chinese patients who had PD after 1[st] line treatment in ENSURE were enrolled. Enrolled patients received cross-over treatment as 2[nd] line treatment after 1[st] line PD. The primary endpoint was PFS, defined as the time of randomization in ENSURE to disease progression or death while on 2[nd] line treatment. For patients who had already progressed after 2[nd] line therapy prior to entering this extension study, relevant information would be collected retrospectively. PFS from 1[st] line PD to 2[nd] line PD was also calculated. The study was approved by IRB and all patients signed informed consent. This study was registered in clinicalgrials.gov (NCT02000531). We also retrospectively analyzed the time to 2[nd] line treatment failure (TTF) defined as the time from randomization to discontinuation of 2[nd] line treatment for any reason.
Results:
Forty-five patients (21 from erlotinib arm and 24 from GP arm) were enrolled in the final analysis in this ENSURE extension study. Limited recruitment was mainly due to later initiation of this study (from January to December of 2014), many deaths at the beginning of this study, or unwillingness to sign informed consent by some patients. Age, sex, and ECOG at baseline in erlotinib group and GP group were balanced. Among 45 enrolled subjects, 33 (73.3%) subjects completed the study. There was no significant difference in median PFS from the date of randomization in ENSURE study to 2[nd] line PD for both arms 26.3 (95%CI: 19.8 , 34.0 ) months vs 23.4 (95%CI: 17.8, 39.0 ) months, HR=1.26 (95%CI: 0.61, 2.62), p=0.529). For 2[nd] line cross-over treatment, ORR in erlotinib and GP arms was 33.3% (7PR/21) and 66.7% (16PR/24) respectively (p=0.0377). In a retrospective analysis of 175 patients from the whole ENSURE study, 63.2% patients in erlotinib arm (n=87) received 2[nd] line chemotherapy and 86.4% patients in GP arm (n=88) received 2[nd] line targeted therapy. The median TTF in erlotinib and GP arm were 29.4 (95%CI: 24.7, 34.2) and 24.7 (95%CI: 21.9, 28.4) months respectively (HR=0.74(95%CI: 0.47, 1.17), p=0.192).The subgroup analysis (mutation type, ECOG performance status, gender) for TTF between erlotinib and GP arm showed similar trend to the primary analysis.
Conclusion:
Despite limitations, both median PFS (in prospective analysis) and TTF (in retrospective analysis) for erlotinib patients were numerically larger than that in GP arm. This first cross-over treatment ENSURE extension study further confirms benefits of erlotinib as standard 1[st] line treatment for EGFR mutant NSCLC. It also supports the importance of 1[st] and 2[nd] line treatment sequence of erlotinib and platinum-based chemotherapy for the treatment of EGFR mutant NSCLC.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-051 - Biomarker Analyses from a Phase II Trial of Nab-Paclitaxel/Carboplatin vs Emcitabine/Carboplatin in Advanced Squamous Cell Lung Cancer (ID 2846)
09:30 - 09:30 | Author(s): C. Huang
- Abstract
Background:
The administration of nab-paclitaxel/carboplatin (nab-PC) as first-line therapy in patients with advanced non-small-cell lung cancer (NSCLC) was efficacious and resulted in a significantly improved objective overall response rate (ORR) versus solvent-based PC in a phase Ⅲ trial. However, our phase Ⅱ trial (NCT01236716; CTONG1002), which compared the efficacy and safety of first-line nab-PC with gemcitabine/carboplatin (GC) in advanced squamous cell carcinoma of the lung, only showed a marginally improved ORR caused by first-line nab-PC. Meanwhile, the matricellular glycoprotein SPARC (secreted protein acidic and rich in cysteine) and caveolin-1 are potential biomarkers for advanced NSCLC patients receiving nab-PC. Therefore, we retrospectively aimed to explore their predictive and prognostic value using immunohistochemistry (IHC).
Methods:
From November 2010 to June 2013, 127 untreated patients with locally advanced and metastatic squamous cell carcinoma of the lung were randomly assigned 1:1 to receive first-line nab-PC (nab-P, 135 mg/m[2], d1, d8, q3w; C, AUC = 5, d1, q3w ) or GC (G, 1,250 mg/m[2], d1, d8, q3w; C, AUC = 5, d1, q3w). There were 110 patients evaluable for ORR (nab-PC, 54; GC, 56), 119 evaluable for survival (nab-PC, 57; GC, 62) respectively. However, there were 72 patients with sufficient tissue for IHC of both SPARC and caveolin-1 proteins. Different cut-off values of IHC scoring systems were used to explore predictive and prognostic role of both biomarkers.
Results:
The last follow-up was on January 16, 2015. Considering treatment, when the maximum rank method was used for cut-off values, median progression-free survival (PFS) was 7.5 (95%CI: 2.4~12.6) months in higher SPARC-expression arm and 4.3 (95%CI: 2.2~6.3) months in lower SPARC-expression arm for patients treated with GC, HR=0.43 (95%CI: 0.19~0.94), p = 0.030; Median overall survival (OS) was 20.0 (95%CI: 14.7~25.3) months in lower SPARC-expression arm and 10.1 (95%CI: 6.2~14.0) months in higher SPARC-expression arm for patients treated with nab-PC, HR=2.41 (95%CI: 1.08~5.40), p = 0.027. When average method was used for cut-off values, median OS was 18.2 (95%CI: 9.6~26.8) months in lower SPARC-expression arm and 8.4 (95%CI: 5.1~11.7) months in higher SPARC-expression arm for patients treated with nab-PC, HR=2.46 (95%CI: 1.07~5.65), p = 0.029. Regardless of treatment, when the maximum rank method was used for cut-off values, median OS was 14.5 (95%CI: 6.8~22.1) months in lower SPARC-expression arm and 8.4 (95%CI: 5.3~11.5) months in higher SPARC-expression arm, HR=0.47 (95%CI: 0.27~0.83), p = 0.007. When average method was used for cut-off values, median OS was 14.4 (95%CI: 9.2~19.5) months in lower SPARC-expression arm and 8.4 (95%CI: 5.4~11.4) months in higher SPARC-expression arm, HR=0.48 (95%CI: 0.27~0.87), p = 0.013. ORR was not correlated with expression of SPARC, p＞0.05. However, there were no significant differences in ORR, PFS and OS between higher and lower caveolin-1 expression arms, p＞0.05.
Conclusion:
SPARC expression could be a negative prognostic factor for OS of patients with advanced squamous cell carcinoma of the lung, but was not a predictive factor for ORR and PFS, except for patients treated with GC. However, caveolin-1 expression had neither predictive nor prognostic value.
