Cross over in clinical trials skews up data. This however is a part and parcel of medical ethics. In the AVOREN trial following an interim analysis in December 2006, the superiority of Interferon plus Bevacizumab was significant enough that the study was unblinded and the Data Safety Monitoring Board recommended cross over of patients from placebo group to Bevacizumab group. Further approximately 63% of the patients in the Interferon and placebo group and 55% of the patients in the Interferon and Bevacizumab group went on to receive post protocol second and third line therapies with multitargeted Tyrosine Kinase Inhibitors (MKIs), mTOR inhibitors, cytokines and chemotherapy. This could have had an impact on overall survival results at the time of this analysis.
The RECIST( Response Evaluation Criteria In Solid Tumors ) which measures tumor responses by imaging techniques including X-rays, CT scans and MRIs has been of less value whereas clinical benefit including Progression Free Survival remains more relevant when assessing efficacy of MKIs in metastatic Renal Cancer. The addition of Bevacizumab to Interferon alfa 2a was however not only associated with a significant improvement in progression free survival (10.4 months vs 5.5 months, HR =0.63, P<0.0001) but also overall response rate (31% vs 12%, P<0.0001) compared to Interferon plus placebo. This may be relevant if preoperative treatment for renal cancer is a consideration and this response rate efficacy parameter may also benefit patients who have symptomatic unresectable locally advanced Renal Cancer.
The survival benefit seen with Sunitinib is a major step in the right direction when it comes to treatment of renal cell carcinoma. The median overall survival was 26.4 months for sunitinib-treated patients compared with 21.8 months for IFN-α recipients (P=0.051) and objective response rate was 47% for sunitinib compared with 12% for IFN-alpha (P < .001). This should encourage more patients and convince more treating Oncologists to consider Sutent (Sunitinib) as first line treatment of metastatic Renal Cell Cancer.
The survival benefit with the use of Pemetrexed (Alimta) Maintenance is intriguing and maybe more relevant for patients with non-squamous cell histology.
Pemetrexed (Alimta®) was given as maintenance treatment following four cycles of induction with platinum based combination chemotherapy (without Pemetrexed). Pemetrexed maintenance resulted in improvement in progression free survival as well as overall survival, but these benefits were observed only in patients with non squamous histology.