Treatment of Recurrent Melanoma Following Adjuvant Therapy

In the era of effective therapies in melanoma, notably the widespread use of two types of adjuvant treatments: anti-PD-1 immunotherapies and therapies targeting the mitogen-activated protein kinase pathway, for BRAF-mutant patients, an important question arises about how to treat these patients in case of recurrent melanoma following adjuvant therapy. Prospective data are lacking in this area and might be difficult to obtain due to the constant progress being made in the field. Therefore, we reviewed available data suggesting that the initial adjuvant treatment received and the following events provide information about the biology of the disease and the probability of response to following systemic treatments. Thus, in case of relapse during or just after adjuvant anti-PD-1, immune resistance is probable, an anti-PD-1 monotherapy rechallenge has a low likelihood of clinical benefit, and escalation with a combination of immunotherapies should be given priority. In case of relapse during treatment with BRAF plus MEK inhibitors, there may be a risk of lower efficacy of immunotherapy than in naïve patients since this relapse attests not only to a resistance to BRAF-MEK inhibition, but also the introduction of immunotherapy to rescue a progression on targeted therapy. In case of relapse long after adjuvant treatment cessation, whatever the treatment received, no conclusion can be drawn about the efficacy of these drugs, and these patients can be treated like naïve patients. Thus, a combination of anti-PD-1 and anti-CTLA4 is probably the best solution, and the following line can be BRAF-MEK inhibitors in BRAF-mutated patients. Finally, in case of recurrent melanoma following adjuvant therapy, given the promising upcoming strategies, inclusion in a clinical trial should be offered as frequently as possible.