Time to next treatment or death as a candidate surrogate endpoint for overall survival in advanced melanoma patients treated with immune checkpoint inhibitors: an insight from the phase III CheckMate 067 trial

The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (≥2× upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4–5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.

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402P Detailed clinical course of immune-related hepatotoxicity in advanced melanoma patients using immune checkpoint inhibitors

Annals of Oncology ◽

10.1093/annonc/mdw588.008 ◽

2016 ◽

Vol 27 (suppl_9) ◽

Author(s):

Y. Maruki ◽

S. Kondo ◽

Y. Oshiro ◽

F. Yutaka ◽

K. Namikawa ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Clinical Course ◽

Checkpoint Inhibitors ◽

Advanced Melanoma ◽

Melanoma Patients

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Hyperprogressive disease rarely occurs during checkpoint inhibitor treatment for advanced melanoma

Cancer Immunology Immunotherapy ◽

10.1007/s00262-020-02716-3 ◽

2020 ◽

Author(s):

M. Schuiveling ◽

E. H. J. Tonk ◽

R. J. Verheijden ◽

K. P. M. Suijkerbuijk

Keyword(s):

Tumor Growth ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Evaluation Criteria ◽

Tumor Burden ◽

Advanced Melanoma ◽

Tumor Growth Rate ◽

Biological Entity ◽

Melanoma Patients

Abstract Introduction Hyperprogression, characterized by a rapid acceleration in tumor growth, is a novel pattern of progression recently described in patients treated with immune checkpoint inhibitors. This study aims to assess the incidence of hyperprogression in patients with advanced melanoma treated with checkpoint inhibitors. Methods Clinical and radiological findings of all advanced melanoma patients who started checkpoint inhibitors between January 2013 and March 2019 in a tertiary academic center in the Netherlands were analyzed. Change in tumor burden was calculated by assessing volumetric tumor growth using the criteria as defined by immune Response Evaluation Criteria in Solid Tumors version 1.1. Hyperprogression was defined as a time to treatment failure less than 2 months with doubling of tumor burden and a twofold increase in tumor growth rate during treatment. Possible hyperprogression was defined as the presence of the first two criteria in the absence of a pre-baseline scan. Results Out of 206 treatment episodes in 168 patients, 75 were evaluable for hyperprogression and 87 for possible hyperprogression. Hyperprogression was observed in one patient (1.3%) and possible hyperprogression was observed in one patient (1.1%). Conclusion Hyperprogression is rare in melanoma patients treated with immune checkpoint inhibitors. Our data question if hyperprogression really is a biological entity in metastatic melanoma.

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402P Detailed clinical course of immune-related hepatotoxicity in advanced melanoma patients using immune checkpoint inhibitors

Annals of Oncology ◽

10.1016/s0923-7534(21)00560-3 ◽

2016 ◽

Vol 27 ◽

pp. ix125

Author(s):

Y. Maruki ◽

S. Kondo ◽

Y. Oshiro ◽

F. Yutaka ◽

K. Namikawa ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Clinical Course ◽

Checkpoint Inhibitors ◽

Advanced Melanoma ◽

Melanoma Patients

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Positive progress: current and evolving role of immune checkpoint inhibitors in metastatic triple-negative breast cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920909091 ◽

2020 ◽

Vol 12 ◽

pp. 175883592090909

Author(s):

Christine E. Simmons ◽

Christine Brezden-Masley ◽

Joy McCarthy ◽

Deanna McLeod ◽

Anil Abraham Joy

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Triple Negative Breast Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Triple Negative ◽

Checkpoint Inhibitors ◽

Phase Iii ◽

Current Evidence ◽

First Line

Background: Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with historically poor overall outcomes, due primarily to a lack of effective targeted agents. Chemotherapy has been the primary treatment approach, although immune checkpoint inhibitors (ICIs) are currently being investigated to improve patient outcomes. This review examines the clinical implications of current evidence on the use of ICIs for the treatment of metastatic TNBC. Methods: Our systematic search identified two phase III and five phase I/II trials reporting on the efficacy of ICIs used as monotherapy or combined with chemotherapy for the treatment of metastatic TNBC. Results: The phase III IMpassion 130 trial showed a significant improvement in median progression-free survival in the intent-to-treat (net 1.7 months, p = 0.002) and PD-L1-positive populations (net 2.5 months, p < 0.001) for the addition of first-line atezolizumab versus placebo to nab-paclitaxel in metastatic TNBC. Although median overall survival was not significantly improved in patients receiving atezolizumab overall [net 2.3 months, hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.72–1.02, p = 0.078], numerical improvements in the PD-L1-positive population were compelling (net 7.0 months, HR 0.71; 95% CI 0.54–0.93). Toxicity profiles were as expected, and no new safety signals were observed. Pembrolizumab monotherapy did not significantly improve overall survival in similar patients that had received prior treatment in KEYNOTE-119. Conclusions: Atezolizumab plus nab-paclitaxel represents a potential new first-line standard of care for patients with metastatic PD-L1-positive TNBC. Other ICIs used as monotherapy, or combined with chemotherapy for advanced TNBC, as well as their use for earlier stage disease, are areas of ongoing investigation.

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