370P - Mean overall survival (OS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) of nanoparticle albumin-bound paclitaxel (nab-P) vs con...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Javier Cortes
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors J. Cortes1, X. Ji2, F. Lin3, S. Whiting4, A. Ko5, M. Bravo6, A. Fandi7, M. Botteman2
  • 1Oncology, Vall d'Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 2Outcomes Research, Pharmerit International, Bethesda/US
  • 3Health Economics, Pharmerit International, Bethesda/US
  • 4Health Economics, Celgene, Summit/US
  • 5Biostats, Celgene Corporation, Summit/US
  • 6Biostatistics, Celgene Corporation, Summit/US
  • 7Clinical Research And Development, Celgene Corporation, Summit/US

Abstract

Aim

To compare mean OS and quality-adjusted OS (via Q-TWiST methodology) of nab-P vs sb-P in metastatic breast cancer.

Methods

To estimate quality-adjusted OS, OS observed in a phase III clinical trial (Gradishar et al. J Clin Oncol. 2005) was partitioned into 3 states: time without progression or grade ≥ 3 toxicity (TWiST), time with grade ≥ 3 toxicity (TOX), and time after disease progression (REL). Next, mean quality-adjusted OS (ie, Q-TWiST) was calculated by multiplying the mean time spent in each state by utilities (TWiST = 1.0, TOX = 0.5, and REL = 0.5). In threshold analyses, TOX and REL utilities were varied from 0.0 to 1.0 while maintaining TWiST = 1.0. Comparisons were made for the intent-to-treat (ITT) population and by chemotherapy line, number of metastatic lesions, and baseline age. A relative gain in Q-TWiST (vs mean OS of sb-P) of ≥ 10% was defined as clinically important (Revicki et al. Qual Life Res. 2006).

Results

In the ITT population, nab-P patients (n = 229; vs sb-P, n = 225) experienced non-significant gains of 1.4 months (mo) of mean Q-TWiST (11.6 vs 10.2 mo; 95% CI of difference: −0.03, 2.8) and 1.2 mo of mean OS (17.2 vs 16.0 mo; 95% CI of difference: −0.9, 3.3). In the indicated population of patients receiving > first-line chemotherapy, nab-P has previously shown a significant 2.2 mo median OS benefit (Gradishar et al. J Clin Oncol. 2005). In these patients, nab-P also yielded a significant mean OS benefit of 3.1 mo, which equates to a percentage gain of 23%, [16.4 (n = 132) vs 13.2 mo (n = 136); 95% CI of difference: 0.7, 5.6] and a significant Q-TWiST gain of 2.6 mo (11.2 vs 8.6 mo; 95% CI of difference: 0.7, 4.3), with a relative quality-adjusted OS gain of 19% (range in threshold analysis: 15% - 24%, all significant). A mean OS and Q-TWiST benefit was also observed in other subgroups analyzed, albeit not significant.

Conclusions

In its approved indication of > first-line metastatic breast cancer, nab-P offers a significant mean OS benefit of 3.1 mo, and a clinically important and statistically significant improvement in quality-adjusted OS of 2.5 mo, with a 19% relative gain, vs sb-P.

Disclosure

J. Cortes: Consulting fees (Celgene, Novartis), fees for non-CME services (Roche, Celgene, Novartis, Eisai); X. Ji: Employee of Pharmerit International; Received Professional Fees from Celgene Inc.; F. Lin: Employee of Pharmerit International which received research funding from Celgene for this project; S. Whiting, A. Ko, M. Bravo and A. Fandi: Employment or leadership position and stock ownership, Celgene; M. Botteman: Shareholder and employee of Pharmerit International which received research funding from Celgene for this project