Single-center study under a French Temporary Authorization for Use (TAU) protocol for ipilimumab in metastatic melanoma: negative impact of baseline corticosteroids

Chasset, François; Pagès, Cécile; Biard, Lucie; Roux, J.; Sidina, Irina; Madelaine, Isabelle; Basset-Séguin, Nicole; Viguier, Manuelle; Madjlessi-Ezra, N.; Schneider, Pierre; Bagot, M.; Resche-Rigon, Matthieu; Lebbe, Célèste

doi:10.1684/ejd.2014.2471

Cited by 35 publications

(38 citation statements)

References 42 publications

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“…In total, 346 potentially relevant citations were reviewed (Figure 1). Ultimately, 16 studies published from 2009 to 2019 that reported OS and/or PFS data were included in the final analysis [17,[19][20][21][22][27][28][29][30][31][32][33][34][35][36][37]. The total number of patients included was 4045 ranging from 45 to 1025 patients per study (median, 151).…”

Section: Resultsmentioning

confidence: 99%

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Petrelli

Signorelli

Ghidini

et al. 2020

Cancers

220

156

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Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies, n = 16; patients, n = 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24–1.91; p = 0.01 and HR = 1.34, 95% CI: 1.02–1.76; p = 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41–4.43; p < 0.01) or brain metastases (HR = 1.51, 95% CI 1.22–1.87; p < 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.

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Section: Resultsmentioning

confidence: 99%

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Petrelli

Signorelli

Ghidini

et al. 2020

Cancers

220

156

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“…This is particularly the case with symptomatic intracranial metastases given their neurologic consequences. An added benefit of surgery prior to immunotherapy is the facilitation of steroid discontinuation shortly after surgery and prior to initiation of immunotherapy, which otherwise might impair the effectiveness of immunotherapy . Further studies will be needed to investigate the time to steroid discontinuation between various upfront treatment approaches including surgery and radiosurgery.…”

Section: Discussionmentioning

confidence: 99%

Upfront Surgical Resection of Melanoma Brain Metastases Provides a Bridge Toward Immunotherapy-Mediated Systemic Control

et al. 2019

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Background Immune checkpoint blockade has systemic efficacy in patients with metastatic melanoma, including those with brain metastases (MBMs). However, immunotherapy‐induced intracranial tumoral inflammation can lead to neurologic compromise, requiring steroids, which abrogate the systemic efficacy of this approach. We investigated whether upfront neurosurgical resection of MBM is associated with a therapeutic advantage when performed prior to initiation of immunotherapy. Material and Methods An institutional review board‐approved, retrospective study identified 142 patients with MBM treated with immune checkpoint blockade between 2010 and 2016 at Massachusetts General Hospital, of whom 79 received surgery. Patients were classified based on the temporal relationship between immunotherapy, surgery, and development of central nervous system metastases. Overall survival (OS) was calculated from the date of diagnosis of MBM until death from any cause. Multivariate model building included a prognostic Cox model of OS, the effect of immunotherapy and surgical sequencing on OS, and the effect of immunotherapy and radiation sequencing on OS. Results The 2‐year overall survival for patients treated with cytotoxic T‐lymphocyte antigen 4, programmed death 1, or combinatorial blockade was 19%, 54%, and 57%, respectively. Among immunotherapy‐naïve melanoma brain metastases, surgery followed by immunotherapy had a median survival of 22.7 months (95% confidence interval [CI], 12.6–39.2) compared with 10.8 months for patients treated with immunotherapy alone (95% CI, 7.8–16.3) and 9.4 months for patients treated with immunotherapy followed by surgery (95% CI, 4.1 to ∞; p = .12). On multivariate analysis, immunotherapy‐naïve brain metastases treated with immunotherapy alone were associated with increased risk of death (hazard ratio, 1.72; 95% CI, 1.00–2.99) compared with immunotherapy‐naïve brain metastases treated with surgery followed by immunotherapy. Conclusion In treatment‐naïve patients, early surgical resection for local control should be considered prior to commencing immunotherapy. A prospective, randomized trial comparing the sequence of surgery and immunotherapy for treatment‐naïve melanoma brain metastases is warranted. Implications for Practice In this retrospective study of 142 patients with melanoma brain metastases treated with immune checkpoint blockade, the development of melanoma brain metastases following immunotherapy was associated with decreased survival compared with diagnosis of immunotherapy‐naïve brain metastases. The benefit of surgical intervention was seen in immunotherapy‐naïve brain metastases in contrast to brain metastases that developed on immunotherapy. These results suggest that upfront local control with surgery for immunotherapy‐naïve melanoma brain metastasis may provide a bridge toward immunotherapy‐mediated systemic control.

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“…A review of the literature and a literature search were performed as described by Chasset et al . 4 . Briefly, we searched EMBASE (1974–January 2014), MEDLINE (1966–February 2015) and the Cochrane Database of Systematic Reviews (The Cochrane Library, 2015, issue 1) for original articles without language restrictions.…”

Section: Methodsmentioning

confidence: 99%

Ipilimumab in the real world

et al. 2015

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Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe. We interrogated data from UK EAP patients to inform future clinical practice. Clinicians registered in the UK EAP provided anonymized patient data using a prespecified variable fields datasheet. Data collected were baseline patient characteristics, treatment delivered, toxicity, response, progression-free survival and overall survival (OS). Data were received for 193 previously treated metastatic melanoma patients, whose primary sites were cutaneous (82%), uveal (8%), mucosal (2%), acral (3%) or unknown (5%). At baseline, 88% of patients had a performance status (PS) of 0–1 and 20% had brain metastases. Of the patients, 53% received all four planned cycles of ipilimumab; the most common reason for stopping early was disease progression, including death from melanoma. Toxicity was recorded for 171 patients, 30% of whom experienced an adverse event of grade 3 or higher, the most common being diarrhoea (13%) and fatigue (9%). At a median follow-up of 23 months, the median progression-free survival and OS were 2.8 and 6.1 months, respectively; the 1-year and 2-year OS rates were 31 and 14.8%, respectively. The 2-year OS was significantly lower for patients with poorer PS (P<0.0001), low albumin concentrations (P<0.0001), the presence of brain metastases (P=0.007) and lactate dehydrogenase levels more than two times the upper limit of normal (P<0.0001) at baseline. These baseline characteristics are negative predictors of benefit from ipilimumab and should be taken into consideration before prescription.

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Single-center study under a French Temporary Authorization for Use (TAU) protocol for ipilimumab in metastatic melanoma: negative impact of baseline corticosteroids

Cited by 35 publications

References 42 publications

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Upfront Surgical Resection of Melanoma Brain Metastases Provides a Bridge Toward Immunotherapy-Mediated Systemic Control

Ipilimumab in the real world

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