The effects on survival of adjuvant therapy with a VEGF-TKI after nephrectomy for RCC are uncertain. Survival rates, times and benefits were predicted by medical oncologists at baseline for each patient they recruited to SORCE.
Medical oncologists at 20 sites in ANZ and 12 in the UK answered the following questions at baseline for each patient they recruited: the predicted overall survival rate at 5 years (SR) and predicted overall survival time (ST) without adjuvant sorafenib; and, the predicted absolute improvements in SR and ST with 1 year of adjuvant sorafenib. We used Spearman’s rank correlation (rs) to assess associations, and Wilcoxon signed rank tests to assess differences between the paired SR–ST values. We assumed exponential survival distributions to calculate: (i) % alive at 5-yrs corresponding to ST estimates, and (ii) hazard ratios (HRs) corresponding to predicted benefits on overall survival. We hypothesized that these HRs should be less extreme (numerically larger) than the target HR of 0.75 for disease free survival used to design the trial.
The table shows paired estimates of ST and SR from 61 medical oncologists for 176 of the 1711 SORCE patients. Predictions of survival without sorafenib were similar whether based on ST or SR. The predicted benefits of sorafenib based on SR were moderately correlated with those based on ST, but significantly larger. The proportion of HRs > 0.75 was 51% based on SRs vs 66% based on STs.Table:
|In Years||Calculated % alive at 5-yrs [a]||Estimated % alive at 5-yrs [b]||[a]-[b]||[a] vs [b]|
|Survival without sorafenib||7||61||60||0 (-7 to 9)||0.62|
|(5 to 12)||(50 to 75)||(50 to 70)||p = 0.6||p < .001|
|Improvement with sorafenib||1||6||7||−2 (-6 to 1)||0.53|
|(1 to 5)||(3 to 10)||(5 to 15)||p < .0001||p < .001|
|Hazard Ratio||0.83||0.83||0.76||0.09 (-0.01 to 0.21)||0.41|
|(0.67 to 0.91)||(0.67 to 0.91)||(0.62 to 0.82)||p < .0001||p < .0001|
The predicted benefits of adjuvant sorafenib based on SRs were often larger than hypothesized, and larger than predictions based on ST, which were more consistent with the target HR. These data suggest that predictions of benefit in this setting may be more conservative and plausible when based on ST rather than SR.
Clinical trial identification
Legal entity responsible for the study
NHMRC Clinical Trials Centre, University of Sydney
Cancer Australia, NHMRC, Bayer, CRUK
I.D. Davis: International Patent Application No: PCT/US2004/032147 (NY-ESO-1) through Ludwig Institute for Cancer Research. Research Funding for institution: Astellas Pharma, Exelixis. M.R. Stockler: Research Funding for institution: Astellas Pharma, Celgene, Bayer, Bionomics, Medivation, Sanofi, Pfizer, AstraZeneca, Bristol-Myers Squibb. All other authors have declared no conflicts of interest.