Comparison Between Sequential & Combination Therapies
Although our argument suggests that combination therapies lead to superior outcomes on the strong preclinical basis of enhanced apoptosis from the synergistic mechanisms and increased deepening of responses, long-term data is clearly lacking in the specific aspect that combination therapies provide a survival advantage over single agent therapy. In the current fast-paced era with rapidly adapting practices to novel combination treatment strategies, it may be neither feasible nor ethical to conduct a study randomizing sequential or combination therapies with a primary end point of OS, especially in the scenario with data suggesting that improved depth of response (as seen with combination agents) translates to PFS and OS advantage. The right agent to start with as a single agent is still a question to be answered, if opting for sequential therapy over combination therapy. Addressing this particular question, a retrospective outcome analysis evaluated whether the sequence of treatment with lenalidomide-based therapy followed by bortezomib-based therapy versus bortezomib-based therapy followed by lenalidomide-based therapy improved outcomes. This study presented at the American Society of Hematology (ASH) 2011 meeting included 208 patients and reported that sequence of therapy was not predictive of OS, irrespective of patients receiving lenalidomide followed by bortezomib or vice versa, except in patients with Durie-Salmon 'B' staging at diagnosis. The authors recommended bortezomib-based treatment as first-line therapy in patients who presented with renal failure. On the contrary, a meta-analysis of Phase III trials of bortezomib-based therapies presented at ASH 2011 further suggested that the addition of bortezomib in the induction regimen not only improved response rates but also resulted in improvement of PFS and OS, adding strength to the argument that combination therapies improve response rates and further outcomes.
Expert Rev Hematol. 2012;5(5):533-545. © 2012 Expert Reviews Ltd.