Muphoran (fotemustine)

In 14 treatment arms, bevacizumab was combined with chemotherapy drugs such as fotemustine, dacarbazine, carboplatin/paclitaxel, and temozolomide. In six treatment arms, bevacizumab was combined with targeted medicines such as imatinib, everolimus, sorafenib, erlotinib, and temsirolimus... This study showed that bevacizumab combined with chemotherapy might be effective and well-tolerated in patients with stage III or IV unresectable malignant melanoma. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=304625], identifier [CRD42022304625].

Regorafenib showed significant benefits in terms of OS in paired comparison with several treatments such as bevacizumab (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.21-0.73), bevacizumab plus carboplatin (HR, 0.33; 95%CI, 0.16-0.68), bevacizumab plus dasatinib (HR, 0.44; 95%CI, 0.21-0.93), bevacizumab plus irinotecan (HR, 0.4; 95%CI, 0.21-0.74), bevacizumab plus lomustine (90 mg/m) (HR, 0.53; 95%CI, 0.33-0.84), bevacizumab plus lomustine (110 mg/m) (HR, 0.21; 95%CI, 0.06-0.7), bevacizumab plus vorinostat (HR, 0.42; 95%CI, 0.18-0.99), lomustine (HR, 0.5; 95%CI, 0.33-0.76), and nivolumab (HR, 0.38; 95%CI, 0.19-0.73). Safety analysis showed fotemustine as the best and bevacizumab plus temozolomide as the worst. The results suggested that regorafenib and bevacizumab plus lomustine (90 mg/m) provide improvements in terms of survival but may have poor ORR in patients with recurrent high-grade glioma.

Intracranial ORR was higher in IN-treated MBM patients than with control therapies (nivolumab or ipilimumab plus fotemustine). Incidence of grade 3/4 adverse events in IN-treated MBM patients was: diarrhea or colitis (16%), hepatitis (15%), rash (8%), increased alanine transaminase (8%), increased aspartate aminotransferase (7%), increased lipase (6%), increased amylase (4%), fatigue (3%), hypophysitis (2%), pneumonitis (2%), headache (2%), nausea or vomiting (1%), and neutropenia (1%). IN is an efficacious and safer treatment option for MBM patients, especially for asymptomatic and treatment naïve patients.

Despite being retrospective study and a few pts were treated with LM, there were no differences neither in PFS nor in OS in pts treated with LM vs FM at first or second line. Higher G1-2 thrombocytopenia was shown in the FM group probably due to a higher number of hematology samples collected.

Compared to fotemustine, ipilimumab plus nivolumab significantly improved overall and long-term survival of melanoma patients with asymptomatic brain metastases.

Activation of both pathways leads to the inhibition of fotemustine-induced apoptosis...The pre-clinical verification of in vitro data using xenograft mouse model of MSCs confirmed the clinical relevance of CD133 signal as a therapeutic target for melanoma treatment. In conclusion, our study provides an insight into the mechanisms regulating MSCs growth and chemo-resistance and suggested a clinically relevant approach for melanoma treatment.

Temozolomide and fotemustine (FTM) have been the therapeutic mainstay of melanoma (MM) patients (pts) with BM for over two decades. Funding: Bristol-Myers Squibb. Clinical trial identification: NCT02460068.

In our series, compared to sequential administration, concomitant association of systemic anticancer drugs and palliative RT did not increase toxicity in mMM patients. BRAF inhibitors and RT produced severe infield toxicities. Prospective studies are needed to better characterize the toxicity of each association.