591 Survival rates in Stage IV melanoma patients treated with radiation and immunotherapy differ depending on age and radiation treatment site

BackgroundMelanoma is difficult to treat due to its propensity of evading the immune system. Radiation can be combined with immune checkpoint inhibitors to potentially prolong survival. Radiation has been shown to reduce tumor sizes both at the site of radiation and at non-irradiated lesions, also known as the abscopal effect. However, the interaction of immunotherapy and radiation treatment in melanoma cancer is not well-defined. This study seeks to better characterize factors influencing survival in Stage IV melanoma patients treated with both radiation and immunotherapy.MethodsRetrospective data was collected from melanoma patients receiving both radiation and immunotherapy within 6 months of each other between 2008–2021 at our institution. Patient and treatment characteristics were examined for their influence on overall survival and progression-free survival using the log-rank test on Kaplan Meier survival curves. Radiographic response was assessed according to PERCIST/RECIST criteria and analyzed against patient/treatment characteristics using the Mann-Whitney U Test. For the abscopal effect, the percent changes both before and after radiation treatment were subtracted in non-irradiated lesions to produce a ”delta-delta” percent change to reflect the rate of change in tumor response to radiation treatment.ResultsYounger patients trended towards worse overall (p=0.141) and progression free (p=0.06) survival as well as less favorable PERCIST/RECIST response to radiation (p=.0562) compared to older patients. Combination CTLA-4 and PD-1 inhibition therapy tended to produce better PERCIST/RECIST tumor response (p=0.09), but it did not significantly affect survival times. In addition, there was some lower overall (p=0.22) and significantly lower progression free (p=0.012) survival among patients with intracranial irradiated lesions. However, no difference was found in PERCIST/RECIST response in the irradiated lesions between the intra- or extracranial groups. Non-irradiated lesions in patients with extracranial irradiated lesions had a pattern of less favorable rate of change in tumor size (p=0.16).ConclusionsLower survival times in younger patients is unexpected and may reflect differences in immunotherapy response in patients receiving both radiotherapy and immunotherapy, which requires further investigation. Combination CTLA-4 and PD-1 inhibition therapy correlating with better tumor response confirms the effect is still present in this cohort receiving radiotherapy. The lower survival times among intracranial lesion patients is most likely due to lower expectancy of brain metastasized patients; however, it could also be the brain is less responsive to immunotherapy. Further research in a larger cohort is needed for deeper analysis, but this series is still comparable in size to other published series.Ethics ApprovalThis retrospective review was approved by the University IRB, UMCIRB 15-001726. Consent of participants was waived due to the retrospective nature of this review.

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A large first-line, randomized, dose-finding, phase II study on thymosin-alpha 1 (T-alpha 1) plus dacarbazine (DTIC) with or without interferon-alpha (IFN-alpha) compared to DTIC plus IFN-alpha in stage IV melanoma. Tumor response and survival results

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8535 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8535-8535 ◽

Cited By ~ 6

Author(s):

R. Camerini ◽

A. Mackiewicz ◽

A. Testori ◽

U. Trefzer ◽

J. Jassem ◽

...

Keyword(s):

T Cell ◽

Null Hypothesis ◽

Tumor Response ◽

Stage Iv ◽

Control Group ◽

First Line ◽

Ifn Alpha ◽

Thymosin Alpha 1 ◽

Melanoma Patients ◽

Stage Iv Melanoma

8535 Background: Thymosin alpha 1 is an immunomodulatory compound that promotes T cell maturation and upregulates T cell response. Ta1 showed clinical potential benefit in a previous pilot study in melanoma patients. Methods: Phase II, randomized, stratified, open-study testing different doses of Ta1 in association with DTIC and IFNa, as first-line therapy in stage IV melanoma patients (AJCC 2001) without brain metastases. The primary endpoint is tumor response and secondary overall survival. Four arms were initially planned: DTIC + IFNa + 1.6 or 3.2 mg Ta1, DTIC + 3.2 mg Ta1, and DTIC + IFNa (control group). A dose-response effect in a preliminary analysis on 142 patients led to the addition of a fifth arm with DTIC + IFNa + 6.4 mg Ta1. Ninety-five patients were allocated to each arm to test the hypothesis that P0 = 0.05 vs the alternative hypothesis that P1 = 0.15 (alpha = 5%, within-group statistical analysis, power = 95%). The five groups were analyzed independently one from the other, nine responses representing the minimal threshold for rejecting the null hypothesis Patients received DTIC (800 mg/m2) iv on day 1, Ta1 (1.6, 3.2 or 6.4 mg) sc on days 8–11 and 15–18, and IFNa (3 MIU) sc on days 11 and 18 during 28d cycles. Tumor response was evaluated every two cycles according to RECIST criteria, utilizing a central review. Results: Data of 483 pts (62% M1c; 25% M1b; 13% M1a) from 64 European sites are given in the table . Thirteen and 10 confirmed responses were observed for the DTIC+ 3.2 mg Ta1 and DTIC+ IFNa + 3.2 mg Ta1 arms (vs 5 in the control group) thus rejecting the null hypothesis that P0 = 0.05. No additional toxicity with the addition of Ta1 was observed. Conclusions: These results suggest a potential survival advantage with the addition of Ta1 to ‘standard‘ treatment of stage IV melanoma patients. The role of Interferon alpha in this therapeutic association is debatable. [Table: see text] [Table: see text]

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Phase III Multicenter Randomized Trial of the Dartmouth Regimen Versus Dacarbazine in Patients With Metastatic Melanoma

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.9.2745 ◽

1999 ◽

Vol 17 (9) ◽

pp. 2745-2745 ◽

Cited By ~ 499

Author(s):

Paul B. Chapman ◽

Lawrence H. Einhorn ◽

Michael L. Meyers ◽

Scott Saxman ◽

Alicia N. Destro ◽

...

Keyword(s):

Survival Time ◽

Tumor Response ◽

Stage Iv ◽

Phase Iii ◽

Phase Ii Trials ◽

Phase Iii Trial ◽

Melanoma Patients ◽

Intent To Treat ◽

To Receive ◽

Stage Iv Melanoma

PURPOSE: Several single-institution phase II trials have reported that the Dartmouth regimen (dacarbazine, cisplatin, carmustine, and tamoxifen) can induce major tumor responses in 40% to 50% of stage IV melanoma patients. This study was designed to compare the overall survival time, rate of objective tumor response, and toxicity of the Dartmouth regimen with standard dacarbazine treatment in stage IV melanoma patients. PATIENTS AND METHODS: In this multicenter phase III trial, 240 patients with measurable stage IV melanoma were randomized to receive the Dartmouth regimen (dacarbazine 220 mg/m2 and cisplatin 25 mg/m2 days 1 to 3, carmustine 150 mg/m2 day 1 every other cycle, and tamoxifen 10 mg orally bid) or dacarbazine 1,000 mg/m2. Treatment was repeated every 3 weeks. Patients were observed for tumor response, survival time, and toxicity. RESULTS: Median survival time from randomization was 7 months; 25% of the patients survived ≥ 1 year.There was no difference in survival time between the two treatment arms when analyzed on an intent-to-treat basis or when only the 231 patients who were both eligible and had received treatment were considered. Tumor response was assessable in 226 patients. The response rate to dacarbazine was 10.2% compared with 18.5% for the Dartmouth regimen (P = .09). Bone marrow suppression, nausea/vomiting, and fatigue were significantly more common in the Dartmouth arm. CONCLUSION: There was no difference in survival time and only a small, statistically nonsignificant increase in tumor response for stage IV melanoma patients treated with the Dartmouth regimen compared with dacarbazine. Dacarbazine remains the reference standard treatment for stage IV melanoma.

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