Tailored immunotherapy approach with nivolumab in advanced renal cell carcinoma (TITAN-RCC)

Grimm, Marc-Oliver; Schmidinger, Manuela; Martinez, I. Duran; Schinzari, Giovanni; Esteban, Emilio; Schmitz, Marc; Schumacher, Ulrike; Baretton, Gustavo; Barthélémy, Philippe; Melichar, Bohuslav; Charnley, Natalie; Schrijvers, Dirk; Albigès, Laurence

doi:10.1093/annonc/mdz394.051

Cited by 50 publications

(40 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, salvage ipilimumab with nivolumab after prior anti-PD-1/L1 has been described in patients with renal cell carcinoma (RCC), melanoma and non-small cell lung cancer (NSCLC). [9][10][11][12] All these studies demonstrated ORRs of about 10%-20% and similar TRAE incidences compared with our analysis. The observation that response rates to ipilimumab-anti-PD-1 were similar regardless of prior anti-PD-1/L1 response was also shared by two such studies.…”

Section: Discussionsupporting

confidence: 88%

“…8 Interestingly, in advanced melanoma, non-small-cell lung cancer and metastatic renal cell carcinoma, salvage ipilimumab and nivolumab have lately demonstrated promising anti-tumor activities in patients with prior PD-1 pathway blockade. [9][10][11][12] To evaluate the efficacy and safety of combined CTLA-4 and PD-1 blockade in patients with advanced HCC who failed PD-1 pathway blockade, we conducted an analysis of patients who received a combination of ipilimumab and nivolumab/pembrolizumab after tumor progression on prior anti-PD-1/L-1.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

Wong

Kwok

Tang

et al. 2021

J Immunother Cancer

View full text Add to dashboard Cite

BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

Wong

Kwok

Tang

et al. 2021

J Immunother Cancer

View full text Add to dashboard Cite

show abstract

“…A small retrospective study (n = 17) could not show a substantial benefit of nivolumab plus ipilimumab after progression on first-line nivolumab [72]. Contrarily, the phase II TITAN trial (n = 207) showed a significant ORR benefit for the "immunotherapeutic boost" with 2-4 cycles of nivolumab plus ipilimumab in the first-line as compared to nivolumab monotherapy [73].…”

Section: Io Re-challengementioning

confidence: 95%

Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook

et al. 2020

View full text Add to dashboard Cite

Immunotherapy (IO) has revolutionized the therapy landscape of non-small cell lung cancer (NSCLC), significantly prolonging the overall survival (OS) of advanced stage patients. Over the recent years IO therapy has been broadly integrated into the first-line setting of non-oncogene driven NSCLC, either in combination with chemotherapy, or in selected patients with PD-L1high expression as monotherapy. Still, a significant proportion of patients suffer from disease progression. A better understanding of resistance mechanisms depicts a central goal to avoid or overcome IO resistance and to improve patient outcome. We here review major cellular and molecular pathways within the tumor microenvironment (TME) that may impact the evolution of IO resistance. We summarize upcoming treatment options after IO resistance including novel IO targets (e.g. RIG-I, STING) as well as interesting combinational approaches such as IO combined with anti-angiogenic agents or metabolic targets (e.g. IDO-1, adenosine signaling, arginase). By discussing the fundamental mode of action of IO within the TME, we aim to understand and manage IO resistance and to seed new ideas for effective therapeutic IO concepts.

show abstract

“…Additional evidences of the improved outcome by adding ipilimumab to nivolumab (“boost” cycles) in metastatic RCC patients, with early significant progressive disease (PD) at week 8 or stable disease (SD) or PD at week 16 during nivolumab induction, has been reported in the Titan trial [ 20 ]. Of the 207 patients enrolled in the study, 64.3% (133/207) received at least one “boost” cycle.…”

Section: Discussionmentioning

confidence: 99%

Agnostic evaluation of ipilimumab and nivolumab association: a metanalysis

et al. 2020

View full text Add to dashboard Cite

Background Ipilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively,have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintains a long-lasting effect. Even Ipilimumab, in combination with nivolumab, has demonstrated a significant clinical benefit in multiple tumor types. However, no trial has been designed with the primary endpoint to compare the efficacy of nivolumab plus ipilimumab combined, compared to nivolumab alone. Hence, the added value of ipilimumab in the combination has not clearly been established yet. The aim of this study was to demonstrate the superiority of the combination strategy compared to the single agent therapy. Materials and methods We performed a meta-analysis of Phase I-II-III Clinical Trials, published from 2010 up to 2020, in which the combination of ipilimumab plus nivolumab was compared to nivolumab alone. We extracted ORR, OS and PFS HR on the basis of treatment from the subgroup analysis of each trial. Results A total of 7 trials were included in the present meta-analysis. Overall, 1313 patients were treated with the nivolumab plus ipilimumab combination compared to 1110 patients treated with nivolumabalone. All trials reported the Objective response rate(ORR), no heterogeneity was found among studies and the pooled Odds Ratio was highly in favor of the nivolumab plus ipilimumab combination with respect to nivolumab alone (1.683; 95% CI: 1.407–2.012; P < 0.0001). Three studies were considered for Progression free survival (PFS) analysis, and the pooled Hazard Ratio favored the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.807; 95% CI: 0.719–0.907; P < 0.0001). The Overall survival(OS) endpoint was considered only in 2 trials, and the pooled HR favored, also in this case, the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.87; 95% CI: 0.763–0.997; P = 0.045). Conclusions The combination of ipilimumab plus nivolumab seems to be superior to nivolumab alone in cancer patients, regardless of histology.

show abstract

Tailored immunotherapy approach with nivolumab in advanced renal cell carcinoma (TITAN-RCC)

Cited by 50 publications

References 0 publications

Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook

Agnostic evaluation of ipilimumab and nivolumab association: a metanalysis

Contact Info

Product

Resources

About