Ipilimumab (MDX-010) in the treatment of non-small cell lung cancer

Genova, Carlo; Rijavec, Erika; Barletta, Giulia; Sini, Claudio; Bello, Maria Giovanna Dal; Truini, Mauro; C, Murolo; Pronzato, P.; Grossi, Francesco

doi:10.1517/14712598.2012.681371

Cited by 20 publications

(13 citation statements)

References 38 publications

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“…Although the role of T cells in mediating the response to lung cancer is unclear, CD4 cell infiltration in NSCLC has been associated with a more favourable prognosis, suggesting a potential protective effect (Hiraoka et al , 2006). These observations are further supported by benefits demonstrated in early-stage trials utilising therapies stimulating T-cell activity in NSCLC patients (Genova et al , 2012). …”

Section: Discussionmentioning

confidence: 69%

Prognosis in HIV-infected patients with non-small cell lung cancer

et al. 2013

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Background:We conducted a population-based study to evaluate whether non-small cell lung cancer (NSCLC) prognosis was worse in HIV-infected compared with HIV-uninfected patients.Methods:Using the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare claims, we identified 267 HIV-infected patients and 1428 similar controls with no evidence of HIV diagnosed with NSCLC between 1996 and 2007. We used conditional probability function (CPF) analyses to compare survival by HIV status accounting for an increased risk of non-lung cancer death (competing risks) in HIV-infected patients. We used multivariable CPF regression to evaluate lung cancer prognosis by HIV status adjusted for confounders.Results:Stage at presentation and use of stage-appropriate lung cancer treatment did not differ by HIV status. Median survival was 6 months (95% confidence interval (CI): 5–8 months) among HIV-infected NSCLC patients compared with 20 months (95% CI: 17–23 months) in patients without evidence of HIV. Multivariable CPF regression showed that HIV was associated with a greater risk of lung cancer-specific death after controlling for confounders and competing risks.Conclusion:NSCLC patients with HIV have a poorer prognosis than patients without evidence of HIV. NSCLC may exhibit more aggressive behaviour in the setting of HIV.

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Section: Discussionmentioning

confidence: 69%

Prognosis in HIV-infected patients with non-small cell lung cancer

et al. 2013

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“…At the time that this study was initiated ipilimumab added to carboplatin and paclitaxel improved progression-free survival, overall response, and overall survival in phase 2 trials for advanced stage NSCLC (14, 15). The study included the collection of blood for immune profiling analysis before treatment, after chemotherapy alone, and after chemotherapy plus ipilimumab.…”

Section: Introductionmentioning

confidence: 99%

Immune Activation in Early-Stage Non–Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab

Ready

Healy

et al. 2017

Clinical Cancer Research

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Purpose To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early stage non-small cell lung cancer (NSCLC) patients. Experimental Design This is a single-arm chemotherapy plus phased ipilimumab Phase II study of 24 treatment-naïve patients with Stage IB–IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles. Results Chemotherapy alone had little effect on immune parameters in PBMCs. Profound CD28 dependent activation of both CD4 and CD8 cells was observed following ipilimumab. Significant increases in the frequencies of CD4+ cells expressing activation markers ICOS, HLA-DR, CTLA-4, and PD-1 were apparent. Likewise, increased frequencies of CD8+ cells expressing the same activation markers, with the exception of PD-1, were observed. We also examined 7 resected tumors and found higher frequencies of activated TILs than those observed in PBMCs. Surprisingly, we found 4 cases of pre-existing tumor-associated antigens (TAA) responses against survivin, PRAME, or MAGE-A3 present in PBMC at baseline, but neither increased frequencies nor the appearance of newly detectable responses following ipilimumab therapy. Ipilimumab had little effect on the frequencies of circulating Tregs and MDSCs. Conclusions This study did not meet the primary endpoint of detecting an increase in blood based tumor associated antigen T cell responses after ipilimumab. Collectively, these results highlight the immune activating properties of ipilimumab in early stage NSCLC. The immune profiling data for ipilimumab alone can contribute to the interpretation of immunological data from combined immune checkpoint blockade immunotherapies.

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“…This drug was evaluated in several Phase I/II/III clinical trials and in different tumor types, including prostate cancer, non-small cells lung cancer (NSCLC), renal carcinoma and pancreatic cancer [38,39,40,41]. The efficacy and safety of ipilimumab was most frequently studied in melanoma.…”

Section: Clinical Trials With Immune Checkpoint Blockade Targeted mentioning

confidence: 99%

Immune Checkpoint Blockade in Cancer Treatment: A Double-Edged Sword Cross-Targeting the Host as an “Innocent Bystander”

Gelao

Criscitiello

Espósito

et al. 2014

Toxins

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Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific “immune-related adverse events” (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique “innocent bystander” effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. What do we need going forward to limit immune checkpoint blockade-induced toxicity? Most importantly, we need a better understanding of the roles played by these agents in normal tissues, so that we can begin to predict potentially problematic side effects on the basis of their selectivity profile. Second, we need to focus on the predictive factors of the response and toxicity of the host rather than serially focusing on individual agents. Third, rigorous biomarker-driven clinical trials are needed to further elucidate the mechanisms of both the benefit and toxicity. We will summarize the double-edged sword effect of immunotherapeutics in cancer treatment.

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Ipilimumab (MDX-010) in the treatment of non-small cell lung cancer

Cited by 20 publications

References 38 publications

Prognosis in HIV-infected patients with non-small cell lung cancer

Prognosis in HIV-infected patients with non-small cell lung cancer

Immune Activation in Early-Stage Non–Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab

Immune Checkpoint Blockade in Cancer Treatment: A Double-Edged Sword Cross-Targeting the Host as an “Innocent Bystander”

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