This is an important trial, from the standpoint of the difficulties involved in planning and carrying it out, and the time involved. A few words about the trial. It was published in 2015 and is twice the size of any previously performed and reported study of osteosarcoma. It was published in Annals of Oncology 26: 407-414, 2015.
In 2002 four major oncology groups in the world got together to investigate treatment of osteosarcoma. They were COG (the American Children’s Oncology Group); COSS (the German pediatric oncology group); EOI (European Osteosarcoma Intergroup); SSG( Scandinavian Sarcoma Group).
The standard treatment of Osteosarcoma is chemotherapy (MAP regimen) for several weeks before surgery, and then again after surgery . The plan was to compare the standard chemotherapy treatment in patients who responded to the initial treatment that produced a certain level of cell death (seen on a tissue slide taken during the surgery), with those who had a lesser level of cell death. This latter group was to receive a different regimen after surgery. The measurement endpoint was EFS (event free survival). In other words when progression or spread of the cancer had occurred. Almost all tissues were reviewed by independent pathologists to confirm the diagnosis. After surgery the patients were randomized to one of two paths, with a different drug being used in each of the two paths. The results of treatment following this plan have not yet been reported.
Recruitment to the study began in 2005, and ended in 2011. In the end 2260 patients were recruited from 326 sites in 17 countries. Not all countries or programs that wanted to get patients in could, because of difficulties with the administrative process, cost, and complying with the difficult permission requirements of different countries. Noteworthy the goal of recruitment initially was fewer patients (1400), but after surgery more patients than expected decided not to undergo randomization but stay with the known treatment drugs (by the act of randomization, and it being a controlled study, no one would know which group he was in). By refusing randomization they could no longer be part of the study.
So out of the 2260, 1334 patients with removable osteosarcoma were randomized.
The early conclusion, before publication of the results of the trial, is: “large scale practice-changing randomized, controlled trials can be undertaken in rare cancers by extending the traditional boundaries of collaboration.” But to this date that is the end of the good news. They follow by saying: “A successor study has not yet emerged despite willingness by investigators and other trial groups.” They further state that there is an absence of new testable innovations and it is a major concern.
And for interest, from concept to publication was 13 years.
There were 42 authors in this study. Truly a great achievement. But no treatments or developments new or promising enough to warrant starting such a large study yet again. And if this trial had shown great promise during the trial, the review of results required during such a trial would have ended the trial early allowing those who had not gotten the purported effective drug to receive it. That is a requirement now of all randomized, controlled studies, but it wasn’t always.
Larry Seymour, MD – RISF Board Member
For additional Information:
Annals of Onclology
The European and American Osteosarcoma Study Group