Multigene expression profile for predicting efficacy of cisplatin and vinorelbine in non-small cell lung cancer
Research output: Contribution to journal › Conference abstract in journal › Research › peer-review
Background: There is a need for biomarkers to predict efficacy of adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC). Presented is a combined cisplatin and vinorelbine marker from a previously validated model system [1] tested in two cohorts.
Methods: The profiles consist of correlated in vitro cytotoxicity of cisplatin and vinorelbine and mRNA expressions. Then each profile is correlated to mRNA expression of 3500 tumors. The cohorts are 1) a publically available dataset with 133 completely resected stage Ib-II NSCLC patients, 71 of whom received adjuvant cisplatin and vinorelbine (ACT) and 62 patients who had no adjuvant treatment (OBS) [2] and 2) 95 stage Ib-IIIb completely resected NSCLC patients who all received adjuvant cisplatin and vinorelbine [3]. Endpoint is cancer specific survival.
Results: The combined cisplatin and vinorelbine profiles scored as a continuous covariate showed 1) a Hazard Ratio (HR) of 0.265 ((95% CI:0.079-0.889), p = 0.032) in the ACT cohort (sensitive versus resistant), and no significant discrimination in the OBS cohort (HR = 1.328 (95% CI:0.46-3.835), p = 0.60). A multivariate model adjusted for stage demonstrated significance for ACT (HR = 0.284 (95% CI:0.086-0.944), p = 0.040) but not for OBS (HR = 1.702 (95% CI: 0.575-5.036), p = 0.34). The combined profiles resulted in 2) a significant prediction for up to 3 years from surgery (HR = 0.143 (95% CI:0.038-0.542), p = 0.004, scored as a continuous covariate). A multivariate model adjusting for stage showed that the predictor remained significant (HR = 0.123 (95% CI:0.030-0.512), p = 0.004). A pooled analysis of the two treated cohorts resulted in a significant prediction (HR = 0.187, (95% CI:0.069-0.508), p = 0.001) up to 3 years from surgery using a random effects model.
Conclusions: The combined profiles demonstrate that NSCLC patients who benefit from cisplatin and vinorelbine can be identified. The profiles did not discriminate patients in the untreated arm. This holds promise for a predictive effect of the profiles and it is currently being validated in a prospective study [4]. [1] PLoS ONE 2016, 11(2): e0148070. [2] Zhu et al JCO 2010;28:4417-4424. [3] ASCO 2016 abstract e20007. [4] AACR 2016 Abstract CT154.
Methods: The profiles consist of correlated in vitro cytotoxicity of cisplatin and vinorelbine and mRNA expressions. Then each profile is correlated to mRNA expression of 3500 tumors. The cohorts are 1) a publically available dataset with 133 completely resected stage Ib-II NSCLC patients, 71 of whom received adjuvant cisplatin and vinorelbine (ACT) and 62 patients who had no adjuvant treatment (OBS) [2] and 2) 95 stage Ib-IIIb completely resected NSCLC patients who all received adjuvant cisplatin and vinorelbine [3]. Endpoint is cancer specific survival.
Results: The combined cisplatin and vinorelbine profiles scored as a continuous covariate showed 1) a Hazard Ratio (HR) of 0.265 ((95% CI:0.079-0.889), p = 0.032) in the ACT cohort (sensitive versus resistant), and no significant discrimination in the OBS cohort (HR = 1.328 (95% CI:0.46-3.835), p = 0.60). A multivariate model adjusted for stage demonstrated significance for ACT (HR = 0.284 (95% CI:0.086-0.944), p = 0.040) but not for OBS (HR = 1.702 (95% CI: 0.575-5.036), p = 0.34). The combined profiles resulted in 2) a significant prediction for up to 3 years from surgery (HR = 0.143 (95% CI:0.038-0.542), p = 0.004, scored as a continuous covariate). A multivariate model adjusting for stage showed that the predictor remained significant (HR = 0.123 (95% CI:0.030-0.512), p = 0.004). A pooled analysis of the two treated cohorts resulted in a significant prediction (HR = 0.187, (95% CI:0.069-0.508), p = 0.001) up to 3 years from surgery using a random effects model.
Conclusions: The combined profiles demonstrate that NSCLC patients who benefit from cisplatin and vinorelbine can be identified. The profiles did not discriminate patients in the untreated arm. This holds promise for a predictive effect of the profiles and it is currently being validated in a prospective study [4]. [1] PLoS ONE 2016, 11(2): e0148070. [2] Zhu et al JCO 2010;28:4417-4424. [3] ASCO 2016 abstract e20007. [4] AACR 2016 Abstract CT154.
Original language | English |
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Article number | 1187P |
Journal | Annals of Oncology |
Volume | 27 |
Issue number | S6 |
Number of pages | 1 |
ISSN | 0923-7534 |
DOIs | |
Publication status | Published - 1 Oct 2016 |
Event | ESMO Congress - Copenhagen, Denmark Duration: 7 Oct 2016 → 11 Oct 2016 Conference number: 41 |
Conference
Conference | ESMO Congress |
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Number | 41 |
Country | Denmark |
City | Copenhagen |
Period | 07/10/2016 → 11/10/2016 |
ID: 174038058