Neo-adjuvant chemo – study identifies benefits

Every so often, and not often enough in the case of sarcoma, a research study is published which throws up an unexpected answer. Studies like this are a lifeblood in research. Innovative thinking and preparedness to use new approaches to resolving a key question are one thing, but when such a study opens up potential practice-changing ideas we must take notice.

Alessandro Gronchi published the results of the Italian Sarcoma Group study of neo-adjuvant chemotherapy at ESMO on Monday as a late-breaking abstract. I won’t go into the details of the study, those are readily available online. The surprise from the study is that the comparator regime of epirubicin+ifosfamide was superior to all the tailored regimes which formed the experimental arms of the study. The drugs were given to patients with high risk limb and trunk tumours as  three cycles of neoadjuvant treatment prior to surgery and the primary outcome measure was relapse free survival with overall survival also recorded.

Neoadjuvant treatment is not usual practice in soft tissue sarcoma. The epirubicin+ifosfamide combination had been previously trialled by the Italian Sarcoma Group and they had concluded that 3 cycles had a similar effect to 5 cycles. The tailored arms used drugs which are well known in sarcoma treatment and only one of them managed to compare favourably with the epirubicin+ifosfamide combination. That was the newest drug in the study,  trabectedin, which was paired with myxoid liposarcoma.

High grade soft tissue sarcoma frequently recurs after surgery, despite the best efforts of experienced surgeons. Recurrence most frequently involves metastasis which is difficult to treat. Taking every possible step to reduce that risk is welcome. Adjuvant (post operative) chemotherapy has little or no benefit, trials of that treatment go back a long way, all with similar conclusions.

Widespread use of neoadjuvant chemo is not likely to result from this study but it opens the way to further clinical trials with neoadjuvant epirubicin+ifosfamide. There is now justification for its use with high risk patients based on this study alone and I would anticipate that the investigators in the study, which includes some of Europe’s leading sarcoma oncologists, will be looking very hard at the results and thinking seriously of its impact on their practice.

Congratulations to Alessandro Gronchi and Paolo Casali, the innovators who drove this study. It is opening up a new route to deliver patient benefit. Also congratulations to EuroSarc, the collaborative project supported by the European Commission, led by Jean-Yves Blay, which funded the study.