A systematic review and meta‐analysis of locoregional treatments for in‐transit melanoma

Abstract

Dear Editor, We have read the paper by Read et al with great interest. The authors performed a systematic review and meta‐analysis of locoregional treatments for melanoma in‐transit metastases (ITMs). We would like to compliment the authors on this attempt for a comprehensive paper on this topic, but would also like to address some hiatuses in our opinion. First, the authors state to include all studies published between 1980 and 2018. Focusing on the locoregional treatment “isolated limb perfusion” (ILP), missing is a study by Madu et al, a retrospective analysis of 91 stage IIIB/IIIC melanoma patients who underwent ILP for ITMs. Although in this, tumor necrosic factor‐α was not routinely used and normothermia was more frequently used than hyperthermia, it still resulted in a significant overall response rate (ORR) of 81% (including a complete response rate of 47%). Nowhere in the paper do the authors discuss the differences between ILP protocols used worldwide (type of drug[s] used, dose of drugs used, duration of ILP, temperature used, etc), and we believe this should be addressed in such a comprehensive paper especially in light of differences in approval, complication rates, and availability of this procedure worldwide. Second, we would like to comment on the exclusion of novel treatments, which in our opinion is essential to mention in this systematic review. Especially treatment with talimogene laherparepvec (T‐VEC), an oncolytic immunotherapy, has shown impressive results. As mentioned in the review, it was approved by the Food and Drug Administration in 2015 and since then has been used worldwide outside of clinical trials. Although it is not available (not reimbursed) or restricted in Australia, T‐VEC is increasingly been shown as a therapy with superior results with relatively mild side effects, and therefore, should be added to this review. Table 1 shows all literature evaluating treatment of ITMs with T‐VEC, using the same inclusion criteria as the author’s review. Like the other locoregional treatments mentioned in the review, T‐VEC can achieve ORR of 56% to 89%, with the difference that T‐VEC responses have the potential to be durable. Real‐world results seem to outperform the OPTiM study results, likely due to patient selection. As this treatment option is being increasingly used in the clinic, we believe it would be an omission to ignore this data in comparison with the other locoregional treatment options. Finally, systemic treatment options have not been presented by the authors and are also being more frequently used in clinical practice. It is unknown what the best locoregional and/or systemic treatment option is for melanoma patients with ITMs in terms of ORR and long‐term survival. A prospective randomized controlled trial would be needed to analyze this, but is not likely to be conducted any time soon. Therefore, including these data in such systematic review and meta‐analysis is crucial.