A Novel Phase Ii Trial of Ipilimumab, Carboplatin and Etoposide (Ice) for the First Line Treatment of Extensive Stage Small Cell Lung Cancer (Sclc)

Ottensmeier, Christian H.; Galea, Ian; Cross, Nadia; Maishman, Tom; Hamid, Debbie; Cave, Judith; Wheater, Matthew; Geldart, Thomas; Mulatero, C; Potter, V.; Danson, Sarah; Woll, P.J.; Griffiths, Richard W.; Nolan, Luke

doi:10.1093/annonc/mdu355.15

Cited by 3 publications

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“…Ongoing trials are investigating the use of ipilimumab in combination with other therapies, including carboplatin and etoposide, radiotherapy, and nivolumab ( Table 2). An open-label phase II study (NCT01331525) of ipilimumab in conjunction with carboplatin and etoposide in ED-SCLC is ongoing, with a primary endpoint of 1-year PFS [40].To date, 39 of 40 patients have been enrolled. In a preliminary analysis, 61% of patients experienced adverse events of grade 3 or above, among which 42% were possibly ipilimumab-related.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

The Future of Immunotherapy in the Treatment of Small Cell Lung Cancer

2016

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Small cell lung cancer (SCLC), which accounts for 10%-15% of lung cancer cases, is an aggressive disease characterized by rapid growth and early widespread metastasis. Although up to 80% of patients respond to first-line chemotherapy, most eventually relapse, and there are no approved agents beyond the second line. Despite the high incidence of mutations in SCLC, to date no targeted therapy has shown a benefit for this patient population, and systemic treatment has not changed significantly during the past 3 decades. Given that extensive-stage SCLC has a 5-year survival rate of only 1%-2%, novel therapies are desperately needed. Recent evidence shows that the immune system is capable of generating antitumor responses against various tumors, including lung cancer, suggesting that immunotherapy may be a viable therapeutic approach to the treatment of patients with SCLC. Of the immunotherapies being investigated for patients with SCLC, antibodies that target the programmed cell death protein-1 (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte antigen-4 (ipilimumab) immune checkpoint pathways are perhaps the most promising. Because these immune checkpoint pathways, which under normal circumstances function to protect healthy tissues from damage during inflammatory responses and maintain self-tolerance, can help tumor cells evade elimination by the immune system, they represent potential therapeutic targets.This review discusses the rationale for immunotherapy and the early clinical results of immunotherapeutic agents being investigated in SCLC. The Oncologist 2016;21:910-921 Implications for Practice: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype. Despite sensitivity to first-line chemotherapy, SCLC has high recurrence rates, and responses to second-line treatments are poor. Recent evidence shows that the immune system is capable of generating responses against various tumors, including lung cancer, suggesting that immunotherapy may be a viable approach for patients with SCLC. Of several immunotherapies being investigated, antibodies that target the programmed cell death protein-1 (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte antigen-4 (ipilimumab) immune checkpoint pathways are among the most promising for patients with SCLC and are the focus of this review.

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Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

The Future of Immunotherapy in the Treatment of Small Cell Lung Cancer

2016

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“…Another patient with melanoma treated with ipilimumab and nivolumab combination therapy developed paraneoplastic acral vascular syndrome [ 15 ]. In a preliminary analysis of an ongoing phase II study (NCT01331525) of ipilimumab with carboplatin and etoposide in SCLC, 61% of patients experienced grade 3 or higher adverse effects, 42% of which were deemed possibly ipilimumab related [ 16 ]. This is higher than the 31% rate of greater than or equal to grade 3 toxicity determined by a recent meta-analysis of 48 trials [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Two patients in the prelim analysis had ipilimumab-related neurological events. One of these was fatal, presenting like an anti-Hu-mediated paraneoplastic syndrome [ 16 ]. A phase I/II multicenter, open-label trial, Checkmate-032, demonstrated a durable response in patients with relapsed SCLC treated with nivolumab ± ipilimumab [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Checkpoint Inhibitor use in Two Heart Transplant Patients with Metastatic Melanoma and Review of High-Risk Populations

2018

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Due to the unique side-effect profile of immune checkpoint inhibitors (ICIs), groups of patients deemed to be at high risk of complications were excluded from trials that proved the efficacy and safety of these agents in patients with various malignancies. Among these excluded patients were those with prior solid organ transplantation, chronic viral infections and pre-existing autoimmune diseases including paraneoplastic syndromes. We present follow-up on a patient from a previously published case report with an orthotopic heart transplantation who was treated with both cytotoxic T-lymphocyte antigen 4 and PD-1 inhibition safely, without organ rejection. Additionally, we describe the case of a patient with a cardiac allograft who also did not experience organ rejection after treatment with pembrolizumab. Through smaller trials, retrospective analyses, case series and individual case reports, we are accumulating initial data on how these agents are tolerated by the aforementioned groups. Our survey of the literature has found more evidence of organ transplant rejection in patients treated with PD-1 inhibitors than those treated with inhibitors of cytotoxic T-lymphocyte antigen 4. Patients with chronic viral infections, especially hepatitis C, seem to have little to no risk of treatment-related increase in serum RNA levels. The literature contains few documented cases of devastating exacerbations of pre-existing autoimmune disease during treatment with ICIs, and flares seem to be easily controlled by immunosuppression in the vast majority of cases. Last, several cases allude to a promising role for disease-specific antibodies and other serum biomarkers in identifying patients at high risk of developing certain immune-related adverse events, detecting subclinical immune-related adverse event onset, and monitoring treatment response to immunosuppressive therapy in patients treated with ICIs. Though these excluded populations have not been well studied in randomized placebo-controlled trials, we may be able to learn and derive hypotheses from the existing observational data in the literature.

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Immunotherapy era in the treatment of small cell lung cancer

Araz

Eryılmaz

2021

Med Oncol

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A Novel Phase Ii Trial of Ipilimumab, Carboplatin and Etoposide (Ice) for the First Line Treatment of Extensive Stage Small Cell Lung Cancer (Sclc)

Cited by 3 publications

References 0 publications

The Future of Immunotherapy in the Treatment of Small Cell Lung Cancer

The Future of Immunotherapy in the Treatment of Small Cell Lung Cancer

Checkpoint Inhibitor use in Two Heart Transplant Patients with Metastatic Melanoma and Review of High-Risk Populations

Immunotherapy era in the treatment of small cell lung cancer

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