Nab-paclitaxel marginally superior to dacarbazine for metastatic melanoma

The study by Hersh et al. was conceived prior to the success of immune checkpoint inhibitors and targeted therapies for melanoma. The treatment landscape has changed rapidly, and the current role of chemotherapy, and nab-paclitaxel specifically, is uncertain.

In the last 5 years, four classes of therapies have significantly improved overall survival over dacarbazine: ipilimumab (HR, 0.72; P less than .001), vemurafenib (HR, 0.37; P less than .001), trametinib (HR, 0.54; P = .01), and nivolumab (HR, 0.42; P less than .001).

For the large majority of patients, chemotherapy would not be considered for the first line of therapy. Patients typically considered for chemotherapy would have failed or would have been intolerant to ipilimumab and an anti-PD1 agent, as well as BRAF/MEK inhibitors if the tumors were BRAF-mutation positive. In these heavily pretreated patients, however, toxicities associated with chemotherapy may outweigh benefits.

In patients with a history of autoimmune disease, some have suggested checkpoint inhibitors may exacerbate these conditions. However, recent retrospective studies suggest that ipilimumab is safe for patients with autoimmune disorders such as inflammatory bowel disease and rheumatoid arthritis.

The current study did not include quality of life data, and given the lack of improvement in overall survival, the superiority of nab-paclitaxel over dacarbazine has not been shown definitively.

Chemotherapy may have a role in combination with targeted or immunotherapeutic agents. Checkpoint inhibitors may be more active in patients with baseline tumor-infiltrating lymphocytes (TILs) and tumor PDL1 expression. Chemotherapy may induce TILs in tumors where the cells are low or absent, and nab-paclitaxel may be a good candidate to explore such combinations.

It remains to be determined if chemotherapy offers greater benefit than the many other strategies under consideration. This brings to the forefront the urgent need for preclinical models to enable comparisons of combination strategies.

Dr. Matteo Carlino is a clinical senior lecturer at the Sydney Medical School, University of Sydney and a medical oncologist at Westmead Hospital and Blacktown Hospital, Australia. Dr. Georgina Long is an associate professor and medical oncologist at Melanoma Institute Australia, University of Sydney. These remarks were part of an editorial accompanying the report (Ann Oncol. 2015 Sep 15. doi: 10.1093/annonc/mdv361). Dr. Carlino and Dr. Long reported having no disclosures.