Abstracts 1
1 Comparative effectiveness of 2nd-line targeted therapies for metastatic renal cell carcinoma: analysis of two practice-based chart reviews
J.E. SIGNOROVITCH*, N.J. VOGELZANG† , S.K. PAL‡, P.L. LIN*, D.J. GEORGE§, M.K. WONG¶, Z. LIU**, X. WANG**, K. CULVER**, J.A. SCOTT†† and E. JONASCH‡‡ *Analysis Group, Inc., Boston, MA, USA; †US Oncology Research, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA; ‡City of Hope Comprehensive Cancer Center, Duarte, CA, USA; §GU Oncology, Duke Cancer Institute, Durham, NC, USA; ¶University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; **Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; ††Cardinal Health, Grand Prairie, TX, USA; ‡‡MD Anderson Cancer Center, Houston, TX, USA
Background: Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study aimed to compare practice-based effectiveness of these therapies in a recent chart review, and to compare findings with a previous chart review (Yang et al. 2012. ASCO). Methods: Community-based medical oncologists/hematologists (N = 36) reviewed charts for ≤15 patients each. Included patients were aged ≥18 years, received a 1st-line TKI and initiated 2nd-line targeted therapy in 2010 or later. The primary outcome was time from 2nd-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving 2nd-line everolimus (EVE), temsirolimus (TEM), or TKI as a class (sunitinib, sorafenib, pazopanib or axitinib), using a multivariable Cox proportional hazards model adjusting for characteristics including type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled with previously-reported HRs for progression-free survival (PFS) from a previous chart review in a meta-analysis. Results: A total of 138, 64 and 79 patients received 2nd-line therapy with EVE, TEM or a TKI, respectively. Mean age was 63 years, mean duration of mRCC 13.5 months, and median follow-up 6 months. After adjusting for baseline characteristics, © 2013 The Authors BJUI © 2013 BJU International | 112, Supplement 3, 1–17
EVE was associated with a 28% and 26% reduction in the hazard of TTF compared to TEM and TKI, respectively. Pooling both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (Table). TTF differences between TEM and TKI were not significant. Conclusions: In two retrospective chart reviews EVE was associated with consistently reduced hazards of 2nd-line treatment failure in mRCC compared to TEM and TKIs. Treatments/ Data EVE vs. TEM Previous Current Pooled EVE vs. TKI Previous Current Pooled
HR (95% Confidence Interval) 0.73 (0.54, 0.97) 0.72 (0.45, 1.16) 0.73 (0.57, 0.93) 0.76 (0.55, 1.04) 0.74 (0.48, 1.15) 0.75 (0.58, 0.97)
2 Survival following initiation of everolimus for 2nd-line treatment of metastatic renal cell carcinoma: prognostic factors in clinical practice and comparison to clinical trials
M.K. WONG*, E. JONASCH†, S.K. PAL‡, J.E. SIGNOROVITCH§, P.L. LIN§, Z. LIU¶, X. WANG¶, K. CULVER¶, J.A. SCOTT**, D.J. GEORGE†† and N.J. VOGELZANG‡‡ *University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; †MD Anderson Cancer Center, Houston, TX, USA; ‡City of Hope Comprehensive Cancer Center, Duarte, CA, USA; §Analysis Group, Inc., Boston, MA, USA; ¶ Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; **Cardinal Health, Grand Prairie, TX, USA; ††GU Oncology, Duke Cancer Institute, Durham, NC, USA; ‡‡US Oncology Research, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA
for patients initiating 2nd-line EVE between 2009 and 2011 following a 1st-line tyrosine kinase inhibitor (TKI). OS was defined as time from EVE initiation to death (censored at last follow-up). In the 1st sample of charts (the study sample), prognostic factors were identified via multivariable Cox proportional hazards models with stepwise selection. Prognostic factors considered included age, duration of mRCC and 1st-line treatment, metastatic sites, diabetes, histological subtype, ECOG and KPS score, and progression during 1st-line treatment. Model performance was assessed in the 2nd sample (the validation sample). Kaplan-Meier (KM) estimates for OS were compared between chart data and RECORD-1. Results: The study and validation samples included 220 and 97 patients, respectively. Significant prognostic factors were clear cell histology (hazard ratio (HR) = 2.9), KPS score
1 Comparative effectiveness of 2nd-line targeted therapies for metastatic renal cell carcinoma: analysis of two practice-based chart reviews
J.E. SIGNOROVITCH*, N.J. VOGELZANG† , S.K. PAL‡, P.L. LIN*, D.J. GEORGE§, M.K. WONG¶, Z. LIU**, X. WANG**, K. CULVER**, J.A. SCOTT†† and E. JONASCH‡‡ *Analysis Group, Inc., Boston, MA, USA; †US Oncology Research, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA; ‡City of Hope Comprehensive Cancer Center, Duarte, CA, USA; §GU Oncology, Duke Cancer Institute, Durham, NC, USA; ¶University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; **Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; ††Cardinal Health, Grand Prairie, TX, USA; ‡‡MD Anderson Cancer Center, Houston, TX, USA
Background: Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study aimed to compare practice-based effectiveness of these therapies in a recent chart review, and to compare findings with a previous chart review (Yang et al. 2012. ASCO). Methods: Community-based medical oncologists/hematologists (N = 36) reviewed charts for ≤15 patients each. Included patients were aged ≥18 years, received a 1st-line TKI and initiated 2nd-line targeted therapy in 2010 or later. The primary outcome was time from 2nd-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving 2nd-line everolimus (EVE), temsirolimus (TEM), or TKI as a class (sunitinib, sorafenib, pazopanib or axitinib), using a multivariable Cox proportional hazards model adjusting for characteristics including type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled with previously-reported HRs for progression-free survival (PFS) from a previous chart review in a meta-analysis. Results: A total of 138, 64 and 79 patients received 2nd-line therapy with EVE, TEM or a TKI, respectively. Mean age was 63 years, mean duration of mRCC 13.5 months, and median follow-up 6 months. After adjusting for baseline characteristics, © 2013 The Authors BJUI © 2013 BJU International | 112, Supplement 3, 1–17
EVE was associated with a 28% and 26% reduction in the hazard of TTF compared to TEM and TKI, respectively. Pooling both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (Table). TTF differences between TEM and TKI were not significant. Conclusions: In two retrospective chart reviews EVE was associated with consistently reduced hazards of 2nd-line treatment failure in mRCC compared to TEM and TKIs. Treatments/ Data EVE vs. TEM Previous Current Pooled EVE vs. TKI Previous Current Pooled
HR (95% Confidence Interval) 0.73 (0.54, 0.97) 0.72 (0.45, 1.16) 0.73 (0.57, 0.93) 0.76 (0.55, 1.04) 0.74 (0.48, 1.15) 0.75 (0.58, 0.97)
2 Survival following initiation of everolimus for 2nd-line treatment of metastatic renal cell carcinoma: prognostic factors in clinical practice and comparison to clinical trials
M.K. WONG*, E. JONASCH†, S.K. PAL‡, J.E. SIGNOROVITCH§, P.L. LIN§, Z. LIU¶, X. WANG¶, K. CULVER¶, J.A. SCOTT**, D.J. GEORGE†† and N.J. VOGELZANG‡‡ *University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; †MD Anderson Cancer Center, Houston, TX, USA; ‡City of Hope Comprehensive Cancer Center, Duarte, CA, USA; §Analysis Group, Inc., Boston, MA, USA; ¶ Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; **Cardinal Health, Grand Prairie, TX, USA; ††GU Oncology, Duke Cancer Institute, Durham, NC, USA; ‡‡US Oncology Research, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA
for patients initiating 2nd-line EVE between 2009 and 2011 following a 1st-line tyrosine kinase inhibitor (TKI). OS was defined as time from EVE initiation to death (censored at last follow-up). In the 1st sample of charts (the study sample), prognostic factors were identified via multivariable Cox proportional hazards models with stepwise selection. Prognostic factors considered included age, duration of mRCC and 1st-line treatment, metastatic sites, diabetes, histological subtype, ECOG and KPS score, and progression during 1st-line treatment. Model performance was assessed in the 2nd sample (the validation sample). Kaplan-Meier (KM) estimates for OS were compared between chart data and RECORD-1. Results: The study and validation samples included 220 and 97 patients, respectively. Significant prognostic factors were clear cell histology (hazard ratio (HR) = 2.9), KPS score
