Cisplatin-vinblastine-temozolomide regimen for patients with relapsed-refractory melanoma who are ineligible for clinical trials: A tertiary care center experience.
Authors: Doolittle Woo Kyung Lee , Trybula Marcus , Sheng Iris Yeong- Fung , Rothermel Luke Daniel , Sidiropoulos Jessica , Goolamier Gordon , Costello Taylor M , Mangla Ankit 
Published: July 2024

e21540 Background: Immune checkpoint inhibitors (IO) are at the forefront of treating patients with melanoma. Upon relapse, enrollment in clinical trials is encouraged. However, most trials in melanoma exclude those with prior IO-related grade 3/4 toxicities, active brain metastasis or poor performance status (PS). Lack of social support or insurance barriers are other issues preventing clinical trial enrollment. Cisplatin-Vinblastine-Temozolomide (CVT) was used extensively in the pre-IO era. Here, we report our experience with the CVT regimen in trial-ineligible patients with relapsed refractory melanoma (RRM). Methods: We conducted a retrospective review of patients with RRM who received CVT regimen. The regimen included Cisplatin (20mg/m2) + Vinblastine (1.5mg/m2) (both Day 1-3) + Temozolomide (125mg/m2) (Day 1-5) with peg-filgrastim support. All patients received at least 1 cycle of chemotherapy. Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were recorded. Overall response rate (ORR) (CR+PR) at 3-months was the primary endpoint; and progression free survival (PFS), overall survival (OS), intracranial (IC) PFS, clinical benefit rate (CBR), ICRR, and toxicity at 3-months were secondary endpoints. Reason for trial ineligibility was also recorded. Results: Ten patients received CVT regimen for a median of 4 cycles (Interquartile range (IQR): 2-6). Five patients had cutaneous, 3 had acral and 2 had mucosal melanoma. Six were men, and 9 were white. Median follow up after starting CVT was 7.5 months (IQR: 2-14). At 3 months, 1 patient had CR, 4 had PR, and 2 had SD. ORR was 50% and overall CBR was 70% at 3-months. Median PFS was 5 months (IQR: 1-11). Four patients needed dose reduction due to myelosuppression. Two patients with PR discontinued CVT after 2 cycles (grade 3 fatigue). Upon progression, 8 patients with RRM had brain metastasis. Six patients got stereotactic radiation prior to starting CVT, and SD was recorded in these patients. The other 2 patients had CR in the brain metastasis with CVT (ICRR-25%). ICCBR was 100% at 3-months. The median ICPFS was 7 months (IQR (3-15). Three patients with acral melanoma were ineligible due to histology, 2 declined to participate (long commute, poor PS), 6 patients had prior grade 4 IO-related toxicity, and 2 patients were not supported by insurance. Two patients with PD (both acral melanoma) were later on enrolled in phase 1 clinical trial upon availability. Conclusions: In patients with RRM, CVT is an effective and well-tolerated regimen which can serve as a bridge till a trial becomes available. Our study also identifies potential barriers to enrollment on clinical trials where insurance issues and prior IO-related toxicity stand out as a major barrier. Real-world studies are needed to gain more insight into the potential barriers to trial enrollment.