Chemo-immunotherapy combination after PD-1 inhibitor failure improves clinical outcomes in metastatic melanoma patients.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 138-138
Author(s):  
Jesus Vera Aguilera ◽  
Jonas Paludo ◽  
Jarrett Failing ◽  
Robert R. McWilliams ◽  
Lisa A. Kottschade ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Clinical Outcomes ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Efficacy And Safety ◽  
Wild Type ◽  
Lung Cancer Patients ◽  
Melanoma Patients

138 Background: Clinical management of metastatic melanoma (MM) after PD-1 blockade failure remains challenging and lacks a standard of care. Chemo-immunotherapy (CIT) combinations have demonstrated favorable efficacy and safety profiles in lung cancer patients. In this study, we compared the clinical outcomes of CIT with immunotherapy or chemotherapy alone after PD-1 blockade failure. Methods: We reviewed MM patients seen at Mayo Clinic between Jan, 2012 and Jun, 2018 who failed anti-PD1 therapy and received subsequent CIT, or immune checkpoint inhibitors (ICI) or chemotherapy alone. A total of 60 patients were analyzed, the CIT cohort [n=33 (55%)] treatment consisted of carboplatin/paclitaxel (n=29), nab-paclitaxel (n=2), paclitaxel (n=1), and temozolomide (n=1). In the ICI (n=9) or chemotherapy alone cohort (n=18) [n=27 (45%)], treatment consisted of carboplatin/paclitaxel (n=11), temozolomide (n=4), nab-paclitaxel (n=3), ipilimumab/nivolumab (n=4), pembrolizumab (n=4), or nivolumab (n=1). Results: Patients in the CIT cohort had a median OS of 3.5 years (95% CI: 1.7-NR) compared to 1.8 years (95% CI: 0.9-2) in the ICI or chemotherapy alone cohort, p=0.02. The median EFS following CIT was 7.6 months (95% CI: 6-10) compared to 3.4 months (95% CI: 2.8-4.1) following either ICI or chemotherapy alone, p=0.0005. A trend towards longer median EFS with use of CIT was seen in patients with BRAF wild-type [median 9 months (95% CI: 6-12)] compared to those harboring a BRAF mutation [median 6.5 months (95% CI: 1.8-9.1), p=0.29]. Side effects were similar among both groups. Conclusions: In MM patients who have failed anti-PD-1 therapy, the CIT combination showed favorable clinical outcomes and acceptable safety profile. This regimen should be considered for MM pts in this setting who have limited treatment options. [Table: see text]

scholarly journals Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0248097
Author(s):  
Patricia M. LoRusso ◽  
Aleksandar Sekulic ◽  
Jeffrey A. Sosman ◽  
Winnie S. Liang ◽  
John Carpten ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Treatment Options ◽  
Standard Of Care ◽  
Wild Type ◽  
Drug Classes ◽  
Pathway Activation ◽  
Comprehensive Genomic Profiling ◽  
Melanoma Patients ◽  
Post Trial ◽  
Selection Of

Although combination BRAF and MEK inhibitors are highly effective for the 40–50% of cutaneous metastatic melanomas harboring BRAFV600 mutations, targeted agents have been ineffective for BRAFV600wild-type (wt) metastatic melanomas. The SU2C Genomics-Enabled Medicine for Melanoma Trial utilized a Simon two-stage optimal design to assess whether comprehensive genomic profiling improves selection of molecular-based therapies for BRAFV600wt metastatic melanoma patients who had progressed on standard-of-care therapy, which may include immunotherapy. Of the response-evaluable patients, binimetinib was selected for 20 patients randomized to the genomics-enabled arm, and nine were treated on the alternate treatment arm. Response rates for 27 patients treated with targeted recommendations included one (4%) partial response, 18 (67%) with stable disease, and eight (30%) with progressive disease. Post-trial genomic and protein pathway activation mapping identified additional drug classes that may be considered for future studies. Our results highlight the complexity and heterogeneity of metastatic melanomas, as well as how the lack of response in this trial may be associated with limitations including monotherapy drug selection and the dearth of available single and combination molecularly-driven therapies to treat BRAFV600wt metastatic melanomas.

Sonography as a Prognostic Indicator of Breslow Depth: Primary Malignant Melanoma of the Auricular Helix

2021 ◽  
pp. 875647932098102
Author(s):  
Shirly Payano-Griffin
Keyword(s):  
Malignant Melanoma ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Prognostic Indicator ◽  
Primary Malignancy ◽  
Irregular Border ◽  
Current Therapies ◽  
Melanoma Patients

Malignant melanoma is a cellular cancer that produces pigmentation of the skin. The tendency toward melanoma may be inherited, and risk factors are increased with overexposure to the sun and ultraviolet radiation. Melanomas commonly present as a dark, asymmetrical, mole-like spot that spreads, with an irregular border. It is uncommon to find a melanoma in the auricular regions and even rarer for it to be a primary malignancy of the auricles. Utilizing sonography to evaluate melanoma lesions could serve as a prognostic indicator, regarding Breslow’s depth, an aide in staging, as well as surgical planning. However, utilizing multiple diagnostic imaging modalities is essential in the proper evaluation and staging of a melanoma. Currently there are revolutionary, effective systemic therapies available for patients with a metastatic melanoma. Current therapies are focused on immunotherapy and checkpoint inhibitors. These treatment options provide an opportunity for selected metastatic melanoma patients to achieve healthy long-term success.

scholarly journals Immune checkpoint inhibitors, endocrine adverse events, and outcomes of melanoma

2022 ◽  
Author(s):  
Hanna Karhapää ◽  
Siru Mäkelä ◽  
Hanna Laurén ◽  
Marjut Jaakkola ◽  
Camilla Schalin-Jäntti ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Outcomes ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Autoimmune Diabetes ◽  
Progression Free Survival ◽  
Electronic Patient Records ◽  
Melanoma Patients

Objective: Immune checkpoint inhibitors (ICI) can cause endocrine adverse events. However, endocrine AEs could be related to better treatment outcomes. Our aim was to investigate whether this holds true in a real-world setting of metastatic melanoma patients. Design: A retrospective single-institution study. Methods: We included 140 consecutive metastatic melanoma patients treated with ICI between January 2012 and May 2019. We assessed endocrine toxicity and best possible treatment outcomes from electronic patient records, including laboratory parameters, and radiological images. Results: Of the treated patients, 21 patients (15%) were treated with ipilimumab, 46 (33%) with nivolumab, 67 (48%) with pembrolizumab, and six (4%) with combination therapy (ipilimumab + nivolumab). Endocrine AEs appeared in 29% (41/140) patients. Three patients had two different endocrine AEs. Thyroid disorders were the most common: 26% (36/140), followed by hypophysitis: 4% (5/140). Three subjects (2%, 3/140) were diagnosed with autoimmune diabetes. Three patients had to terminate treatment due to endocrine toxicity. Radiological manifestations of endocrine AEs were found in 16 patients (39%, 16/41). Endocrine toxicity was associated with significantly better treatment outcomes. Median progression-free survival (8.1 months, range 5.1 – 11.1 months vs. 2.7 months, range 2.4 – 3.0 months, P < 0.001), and median overall survival (47.5 months, range 15.5 – 79.5 months vs. 23.7 months, range 15.3 – 32.1 months, P = 0.035) were longer for patients experiencing endocrine AEs. Conclusions: The higher number of endocrine AEs suggest regular laboratory monitoring aids in AE detection. Endocrine AEs in metastatic melanoma may correlate with better treatment outcomes.

scholarly journals Vitiligo-like Leukoderma as an Indicator of Clinical Response to Immune Checkpoint Inhibitors in Late-stage Melanoma Patients

2021 ◽  
Author(s):  
Sofia Verkhovskaia ◽  
Francesca Romana Di Pietro ◽  
Simona Mastroeni ◽  
Maria Luigia Carbone ◽  
Damiano Abeni ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cox Model ◽  
Immune Therapy ◽  
Group Analysis ◽  
Favorable Outcome ◽  
Clinical Benefits ◽  
Melanoma Patients

Abstract Purpose. Although development of immune checkpoint inhibitors has revolutionized the treatment of metastatic melanoma, more than a half of treated patients experience disease progression during therapy. Cases of spontaneous vitiligo-like leukoderma have been described in melanoma patients and have been associated with a favorable outcome. This vitiligo-like leukoderma can also appear in melanoma patients undergoing immune therapies such as immune checkpoint inhibitors. However, no consensus exists about the relationship between vitiligo-like leukoderma onset and improved overall survival. Our study investigates the possible association between the onset of vitiligo-like leukoderma during immune checkpoint inhibitor treatment and a better prognosis.Methods. A non-concurrent cohort study was conducted by identifying retrospectively 280 patients who had inoperable or metastatic melanoma and had undergone immune therapy with checkpoint inhibitors in any line of treatment. Toxicities developed during therapy were evaluated. Results. Among the 280 study participants, 50% developed at least one type of toxicity, and vitiligo-like leukoderma was observed in 43 patients (15.4%). In the multivariate Cox model, a protective effect for mortality was observed for patients with vitiligo-like leukoderma development (HR = 0.23; 95% CI = 0.11-0.44, p <0.0001). In a sub-group analysis comprising only cutaneous melanoma in first line of treatment (N=153), occurrence of vitiligo-like leukoderma was also an independent predictor factor for duration of clinical benefits measured by time to the next treatment (HR:0.17; 95% CI:0.06-0.44). Conclusion. Our findings indicate that onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome in patients treated with immune checkpoint inhibitors.

scholarly journals Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 616
Author(s):  
Mohamed A. Abd El Aziz ◽  
Antonio Facciorusso ◽  
Tarek Nayfeh ◽  
Samer Saadi ◽  
Mohamed Elnaggar ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Survival Outcomes ◽  
Efficacy And Safety ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Despite the advances in screening protocols and treatment options, hepatocellular carcinoma (HCC) is still considered to be the most lethal malignancy in patients with liver cirrhosis. Moreover, the survival outcomes after failure of first-line therapy for unresectable HCC is still poor with limited therapeutic options. One of these options is immune checkpoint inhibitors. The aim of this study is to comprehensively review the efficacy and safety of immune checkpoint inhibitors for patients with HCC.

scholarly journals Psychological Distress of Metastatic Melanoma Patients during Treatment with Immune Checkpoint Inhibitors: Results of a Prospective Study

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2642
Author(s):  
Lisa Wiens ◽  
Norbert Schäffeler ◽  
Thomas Eigentler ◽  
Claus Garbe ◽  
Andrea Forschner
Keyword(s):  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Female Gender ◽  
Self Assessment ◽  
Prospective Longitudinal Study ◽  
Melanoma Patients ◽  
Prospective Longitudinal

Background: Immune checkpoint inhibitors (ICI) provide effective treatment options for advanced melanoma patients. However, they are associated with high rates of immune-related side effects. There are no data on the distress of melanoma patients during their ICI treatment. We, therefore, conducted a prospective longitudinal study to assess distress and the need for psycho-oncological support in these patients. Methods: Questionnaires were completed before initiation of ICI (T0), after 6–8 weeks (T1), and after 12–14 weeks (T2). We furthermore included the Hornheide Screening Instrument (HSI), distress thermometer (DT), and patients’ self-assessment. Binary logistic regression was performed to identify factors indicating a need for psychooncological support. Results: 36.3%/55.8% (HSI / DT) of the patients were above the threshold, indicating a need for psychooncological support at T0, and 7.8% of the patients reported practical problems. In contrast, at T2, the distress values had decreased to 29.0%/40.2% (HSI/DT), respectively. Female gender and occurrence of side effects significantly correlated to values above the threshold. The strongest factor was the patient’s self-assessment. Conclusion: With the beginning of ICI, psychooncological support should be offered. Furthermore, practical problems should be considered, e.g., transport to therapy. Female patients and patients with side effects should be given special attention, as well as the patient self-assessment.

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