Use and clinical impact of conventional cytotoxic chemotherapy (CTx) subsequent to immunotherapy in metastatic melanoma

Abstract

Background: In recent years the treatment of metastatic melanoma (MM) has changed drastically with the introduction of immunotherapy (ITx) and targeted therapies. Only a minority of patients ( pts) achieve a durable response to such treatments and CTx still has a significant ongoing role to play in the palliative treatment of MM in clinical practice. We aimed to assess the use of CTx in clinical practice since the introduction of ITx and its impact on pts outcome. Method(s): A retrospective database was constructed of all MM pts treated in our institution with ITx between 2011 and 2015 by the systematic cross-match of the Pharmacy and Medical Oncology archives. We then identified pts who received any type of CTx after at least one line of ITx. Objective response rate (ORR) and clinical benefit rate (CBR, including pts with SD for at least 3 months) were assessed using RECIST 1.1 criteria. Overall survival (OS) post ITx and post CTx were calculated. Result(s): Sixty-four pts were treated with ITx between 2011 and 2015. 17 pts (27%) received any type of Ctx post ITx. All pts had documented progressive disease when commenced on CTx. CTx pts characteristics: male 10 (59%), female 7(41%), median age 60 (range 27-72), primary cutaneous 11 (64.7%), ocular 6 (35.3%), BRAF V600 mutation pos 4 (23.5%), ipilumumab-pretreated 16 (94.1%), ipilimumab and anti-PD1-pretreated 4 (23.5%). All BRAF positive pts received BRAF and/or MEK inhibitor in addition to ITx. CTx included single-agent DTIC 8 (47.1%), platinum salts-based poly-CTx 9 (52.9%). Median OS from commencement of CTx was 11 months (range 2-26). ORR (6/17) was 35.3%, CBR (7/17) was 41.2%. CBR in pts who received one vs two lines of ITx was 4/12 (38.5%) vs 3/4 (75%). Conclusion(s): Our analysis shows that in real-world clinical practice about one third of MM pts are still treated with CTx after failure of ITx. Although limited by small numbers and retrospective design, the observed ORR/CBR in our cohort of unselected MM pts suggest that CTx after failure of ITx might have greater activity than in historical series. We are studying the molecular profile of these pts tumours in order to identify potential predictors of improved CTx benefit.