In patients with metastatic melanoma whose disease progressed after immune checkpoint inhibitor (ICI) treatment, chemotherapy produces low response rates and short progression-free survival (PFS), according to a study published in the European Journal of Cancer

The retrospective study included 463 patients with metastatic melanoma who were treated with various chemotherapy regimens after progression on ICI therapy between 2007 and 2017. The patients’ median age at the start of chemotherapy was 59 years. Most patients (60%) were men, 15% had BRAF V600 mutations, 86% had stage M1c disease, and 29% had brain metastases.

The chemotherapy regimens patients received were carboplatin plus paclitaxel (32%), dacarbazine (25%), temozolomide (15%), taxanes alone (9%), fotemustine (6%), and other regimens (13%). About 6% of patients received chemotherapy in combination with BRAF/MEK targeted therapy, immunotherapy, and other combinations.

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The median duration of chemotherapy was 7.9 weeks (range, 0-108 weeks), and the median follow-up was 23 months.

The objective response rate (ORR) was 12.5%. The complete response rate was 0.4%, the partial response rate was 12.1%, and 20.7% of patients had stable disease.

The highest ORR was seen with taxanes alone, at 25.0%. The ORR was 14.3% with carboplatin-paclitaxel, 10.3% with fotemustine, 10.2% with dacarbazine, 2.8% with temozolomide, and 17.2% with the other regimens.

The median PFS was 2.6 months, and the 1-year PFS rate was 12%. The median PFS was 8.7 months in responders.

There were 221 patients who went on to subsequent therapy after chemotherapy, including 110 who received PD-1-directed therapy alone or in combination with ipilimumab, 12 who received ipilimumab alone, and 23 who received ICIs after other therapies. In all, 29 patients responded to subsequent therapy, including 19 who received PD-1-directed therapy.

The median overall survival from the start of chemotherapy to last follow-up was 7.1 months for the entire cohort, 16.8 months for those who responded to chemotherapy, and 6.5 months in nonresponders (P <.0001).

“Chemotherapy has a low response rate and short PFS in patients with metastatic melanoma who have failed checkpoint inhibitor therapy, although activity varied between regimens,” the researchers concluded. “Chemotherapy has a limited role in the management of metastatic melanoma.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Goldinger SM, Buder-Bakhaya K, Lo SN, et al. Chemotherapy after immune checkpoint inhibitor failure in metastatic melanoma: A retrospective multicenter analysis. Eur J Cancer. Published online December 21, 2021. doi:10.1016/j.ejca.2021.11.022