Information on the role of radiotherapy in anti-PD-1 monoclonal antibody-treated melanoma patients is limited. We report on a prospective cohort of advanced melanoma patients treated simultaneously ...with radiotherapy and anti-PD-1 therapy between 01/01/15 and 30/06/16. Tumor evaluations (RECIST 1.1) were performed every 3 months on radiated and non-radiated lesions. Twenty-five advanced melanoma patients (64% AJCC stage IV M1c, 64% on second-line treatment or more, 60% with elevated LDH serum levels) were included. Radiotherapy was performed early (median: 24 days) after the first anti-PD-1 dose in 15 patients with rapidly progressing symptomatic lesion(s) or later (median: 5.4 months) in 10 patients with progressive disease (PD) despite PD-1 blockade. Radiotherapy was limited to one organ in 24 patients and consisted mainly of hypo-fractioned radiotherapy (median dose 26 Gy in 3-5 fractions, 17 patients) or brain radiosurgery (5 patients). Median follow-up after first anti-PD-1 dose was 16.9 m (range 2.7-27.4), with 44% of patients alive at last follow-up. For radiated lesions, rates of complete (CR), partial (PR) responses, stable disease (SD) or PD were 24%, 12%, 24%, and 32%, respectively. For non-radiated lesions, rates of CR, PR, SD, and PD were 20%, 19%, 12%, and 40%, respectively. Responses achieved after radiotherapy for radiated and non-radiated areas were correlated (Pearson correlation r: 0.89, P<0.0001) suggesting an abscopal effect. Five patients with CR remained disease-free after discontinuation of anti-PD-1 for a median of 9.5 months. No unusual adverse event was recorded. Hypo-fractionated radiotherapy may enhance efficacy of anti-PD1 therapy in difficult-to-treat patients. Controlled studies are needed.
To assess the role of radiotherapy in anti-PD-1-treated melanoma patients, we studied retrospectively a cohort of 206 consecutive anti-PD-1 monotherapy-treated advanced melanoma patients (59% M1c/d, ...50% ≥ 3 metastasis sites, 33% ECOG PS ≥ 1, 33% > 1st line, 32% elevated serum LDH) having widely (49%) received concurrent radiotherapy, with RECIST 1.1 evaluation of radiated and non-radiated lesions. Overall (OS) and progression-free (PFS) survivals were calculated using Kaplan−Meier. Radiotherapy was performed early (39 patients) or after 3 months (61 patients with confirmed anti-PD-1 failure). The first radiotherapy was hypofractionated extracranial radiotherapy to 1−2 targets (26 Gy-4 weekly sessions, 68 patients), intracranial radiosurgery (25 patients), or palliative. Globally, 67 (32.5% 95% CI: 26.1−38.9) patients achieved complete response (CR), with 25 CR patients having been radiated. In patients failing anti-PD-1, PFS and OS from anti-PD-1 initiation were 16.8 13.4−26.6 and 37.0 months 24.6−NA, respectively, in radiated patients, and 2.2 1.5−2.6 and 4.3 months 2.6−7.1, respectively, in non-radiated patients (p < 0.001). Abscopal response was observed in 31.5% of evaluable patients who radiated late. No factors associated with response in radiated patients were found. No unusual adverse event was seen. High-dose radiotherapy may enhance CR rate above the 6−25% reported in anti-PD-1 monotherapy or ipilimumab + nivolumab combo studies in melanoma patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Data regarding elderly melanoma patients treated with anti-PD-1 or anti-CTLA-4 antibodies are in favor of tolerability outcomes that are similar to those of younger counterparts. However, there are ...very few studies focusing on elderly patients receiving nivolumab combined with ipilimumab (NIVO + IPI). Here, we ask what are the current prescribing patterns of NIVO + IPI in the very elderly population and analyze the tolerance profile. This French multicenter retrospective study was conducted on 60 melanoma patients aged 80 years and older treated with NIVO + IPI between January 2011 and June 2022. The mean age at first NIVO + IPI administration was 83.7 years (range: 79.3–93.3 years). Fifty-five patients (92%) were in good general condition and lived at home. Two dosing regimens were used: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (NIVO1 + IPI3) in 27 patients (45%) and NIVO 3 mg/kg + IPI 1 mg/kg Q3W (NIVO3 + IPI1) in 33 patients (55%). NIVO + IPI was a first-line treatment in 39 patients (65%). The global prevalence of immune-related adverse events was 63% (38/60), with 27% (16/60) being of grade 3 or higher. Grade ≥ 3 adverse events were less frequent in patients treated with NIVO3 + IPI1 compared with those treated with NIVO1 + IPI3 (12% versus 44%, p = 0.04). In conclusion, the prescribing patterns of NIVO + IPI in very elderly patients are heterogeneous in terms of the dosing regimen and line of treatment. The safety profile of NIVO + IPI is reassuring; whether or not the low-dose regimen NIVO3 + IPI1 should be preferred over NIVO1 + IPI3 in patients aged 80 years or older remains an open question.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Despite its low efficacy, chemotherapy with dacarbazine remains an option in metastatic melanoma patients after failure of immune checkpoint inhibitors (ICI) ± targeted therapy. Some observations ...suggested an increased efficacy of chemotherapy in melanoma or lung cancer patients previously treated with ICI; we aimed to evaluate the efficacy of dacarbazine in a controlled-group study of patients pre-treated or not with ICI.
We retrospectively collected data from all consecutive patients treated with dacarbazine for advanced cutaneous melanoma without brain metastasis, in our skin cancer centre between June 2006 and September 2019. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall response rates (ORR), overall survival (OS) and safety of dacarbazine.
Among 72 patients, 17 (23.6%) received dacarbazine after ICI and 55 (76.3%) without prior ICI. Despite less favourable prognostic factors in patients ICI-pre-treated, median PFS was 4.27 months (range 0.89-43.69) in this group versus 2.04 months (range 1.25-39.25) P = 0.03 in non-ICI-pre-treated patients; ORR were 35.3% and 12.7%, respectively. The median OS and the occurrence of adverse events were similar in both groups.
Dacarbazine seems to offer a short-lived benefit in patients with progressive advanced disease despite ICI (±targeted therapy), and could be an alternative before considering best supportive care.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To evaluate the ability of high-resolution ultrasonography (hrUS) to detect sentinel-node (SN) melanoma metastases preoperatively before sentinel-node biopsy (SNB), to define hrUS resolution, and to ...evaluate which US criteria should be used. During a 6.5-year period, 131 consecutive patients with 132 >or=1-mm thick or ulcerated cutaneous melanomas, who were followed up at a single center, were enrolled. All patients underwent preoperative regional lymph-node hrUS and SNB. We used the recently evaluated ultrasonographic stringent and nonstringent hrUS criteria to detect SN metastases. Sizes of the SN metastatic deposits were measured under light microscopy. Thirty-five (27%) patients had a positive SNB. HrUS identified only three positive SNs as being metastatic. Sensitivity and specificity using stringent criteria were 8.8% 95% confidence interval (CI, 2.3-24.8%) and 95.9% (95% CI, 89.3-98.7%), respectively. Positive-predictive value was 42.9% (95% CI, 11.9-79.9%). The nonstringent criteria provided four additional true-positive results, but lowered specificity (89.8%; 95% CI, 81.6-94.7%) with no significant improvement in sensitivity (20.6%; 95% CI, 9.3-38.4%). Positive-predictive value using nonstringent criteria was 41.2% (95% CI, 19.3-66.4%). HrUS failed to detect all metastatic deposits <5 mm in diameter. HrUS assessment of early-stage melanomas cannot replace surgical SNB. Owing to its low positive-predictive value, hrUS was unable to identify patients who would have to proceed directly to completion lymphadenectomy.
Background
Cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer. Treatment options for inoperable advanced cSCC cases are limited. The efficacy of ...anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAb) has been reported recently in some patients with cSCC.
Objectives
To evaluate the efficacy of anti-PD-1 mAb in a case series of inoperable advanced cSCC and to analyse the efficacy of concurrent radiotherapy.
Materials and Methods
We retrospectively analysed the files of all patients with advanced inoperable cSCC treated with anti-PD-1 mAb and concurrent radiotherapy outside clinical trials in our skin cancer centre before December 31, 2017.
Results
A total of four patients with locally or regionally advanced cSCC were identified. All patients received pembrolizumab at 2 mg/kg every three weeks and concurrent radiotherapy. Two patients who received pembrolizumab as first-line therapy with concurrent radiotherapy (one with skull and leptomeningeal invasion and one with rapidly progressing regional cSCC) had a complete response, allowing treatment discontinuation, without recurrence after a median of 11 months off treatment. All other patients experienced progressive disease. The median progression-free survival and overall survival were 14.4 and 15.6 months, respectively. No toxicity was observed.
Conclusion
There appears to be a place for pembrolizumab as first-line treatment for unresectable or advanced cSCC. Further studies are needed to evaluate concomitant radiotherapy with anti-PD1 antibodies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Immune checkpoint inhibitors (ICI) significantly improve overall survival (OS) in patients with advanced melanoma, but immune-related colitis may occur and warrant anti-tumor necrosis factor α (TNFα) ...treatment in severe forms. A nationwide, multicenter retrospective survey was conducted to assess both, the real-life incidence of grade 3/4 ICI-induced colitis treated with anti-TNFα, in patients with advanced melanoma, and the consequence of this therapeutic strategy on disease outcome. All patients with advanced melanoma treated with anti-TNFα agents for severe ICI-related colitis in the participating centers were included. Relative incidence was calculated according to the total number of patients treated with ICI in network centers during the period of inclusion. The possible impact of anti-TNFα treatment on disease outcome was evaluated through comparison of objective response rate, progression-free survival, and OS with pivotal literature data. Twenty-seven patients from 13 tertiary referral centers were included. Overall, severe ICI-related colitis treated with anti-TNFα occurred in 1% of patients with advanced melanoma, mostly with ipilimumab. Infliximab was successfully used in all patients but 1, mostly after 1 infusion. OS and progression-free survival of 12 and 3 months, respectively, were observed in these patients, along with an objective response rate of 41% at 12 months. This survey shows a low real-life incidence of severe colitis requiring anti-TNFα. Response rates to immunotherapy and survival data do not appear to significantly differ from those observed in pivotal studies. Severe ICI-induced colitis requiring anti-TNFα treatment appears to be a rare event in advanced melanoma, and infliximab does not seem to adversely affect disease outcome.
Advanced melanoma patients who failed anti‐PD‐1 therapy have limited options. We analyzed a cohort of 133 advanced melanoma patients receiving anti‐PD‐1 monotherapy in a referral center between April ...2015 and December 2017, and included the 26 patients with confirmed progressive (PD) or stable disease who received additional radiotherapy with an unmodified anti‐PD‐1 mAb regimen. Tumor evaluations were done on radiated and nonradiated (RECIST 1.1) lesions, with abscopal effect defined as a partial (PR) or complete response (CR) outside radiated fields. Primary endpoint was the CR + PR rate in radiated + nonradiated lesions. Secondary endpoints were progression‐free survival (PFS), melanoma‐specific survival (MSS) and safety. First late radiotherapy, consisting of hypofractionated radiotherapy (3–5 sessions, 20–26 Gy), standard palliative radiotherapy or brain radiosurgery was begun after a median of 6.3 months of anti‐PD‐1 in 23, 2 and 1 patient(s), respectively. Best response was 8 (31%) CR, 2 (8%) profound PR allowing surgical resection of remaining metastases and 16 (62%) PD. Abscopal effect was seen in 35% of patients. Median PFS and MSS since anti‐PD‐1 initiation was 15.2 95% CI: 8.0 not achieved (na) and 35.3 95% CI: 18.5 na months, respectively. PFS curves seemed to achieve a plateau. We discontinued anti‐PD‐1 therapy in 9/10 of patients with no residual evaluable disease and observed one relapse after a median of 10 months off anti‐PD1‐therapy. No unusual adverse event was recorded. Limitations of the study include its retrospective nature and limited size. Hypofractionated radiotherapy may enhance anti‐PD1 monotherapy efficacy in patients who previously failed anti‐PD‐1 therapy. Controlled studies are needed.
What's new?
Hypo‐fractionated radiotherapy may enhance anti‐PD‐1 antibody efficacy, but the findings remain controversial. In this study of 26 consecutive melanoma patients who failed anti‐PD‐1 monotherapy, hypo‐fractionated radiotherapy combined with an unmodified anti‐PD‐1 monoclonal antibody regimen was well tolerated and induced long‐lasting responses, with confirmed complete and partial responses in 10 patients. Progression‐free survival curves achieved a plateau. Anti‐PD‐1 regimen was interrupted in 9 patients achieving response, with only 1 relapse observed after 10 months. This study proposes a new therapeutic strategy after failure of anti‐PD‐1 therapy to rescue patients with metastatic melanoma who have a fairly poor range of treatment options.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK