Standard-dose pembrolizumab in combination with reduced-dose ipilimumab for patients with advanced melanoma (KEYNOTE-029): an open-label, phase 1b trial

Long, Georgina V.; Atkinson, Victoria; Cebon, Jonathan; Jameson, Michael B.; Fitzharris, Bernie; McNeil, Catriona M.; Hill, Andrew; Ribas, Antoni; Atkins, Michael B.; Thompson, John A.; Hwu, Wen Jen; Hodi, F. Stephen; Menzies, Alexander M.; Guminski, Alexander; Kefford, Richard; Kong, Benjamin Y.; Tamjid, Babak; Srivastava, Archana; Lomax, Anna J; Islam, Mohammed Rafiqul; Shu, Xinxin; Ebbinghaus, Scot; Ibrahim, Nageatte; Carlino, Matteo S.

doi:10.1016/s1470-2045(17)30428-x

Cited by 222 publications

(183 citation statements)

References 27 publications

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“…25 In clinical practice, immunotherapy usually was withdrawn anywhere between 6 months and 2 years; however, to the best of our knowledge, the best duration of immunotherapy is uncertain. 27,28 To address this uncertainty, we performed a sensitivity analysis with a maximum treatment duration of 2 years for atezolizumab. 27,28 To address this uncertainty, we performed a sensitivity analysis with a maximum treatment duration of 2 years for atezolizumab.…”

Section: Discussionmentioning

confidence: 99%

First‐line atezolizumab in addition to bevacizumab plus chemotherapy for metastatic, nonsquamous non–small cell lung cancer: A United States–based cost‐effectiveness analysis

Wan

Luo

Tan

et al. 2019

Cancer

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BACKGROUND:The IMpower150 trial found that adding atezolizumab to the combination of bevacizumab and chemotherapy improved survival for patients with metastatic, nonsquamous non-small cell lung cancer (NSCLC). However, considering the high cost of immunotherapy, there is a need to assess its value by considering both efficacy and cost. The current study evaluated the cost-effectiveness of atezolizumab in the first-line setting for the treatment of patients with metastatic NSCLC from the US payer perspective. METHODS: A Markov model was developed to compare the lifetime cost and effectiveness of the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) with the combination of bevacizumab, carboplatin, and paclitaxel (BCP) and carboplatin and paclitaxel (CP) in the first-line treatment of patients with metastatic NSCLC. Life-years (LYs), qualityadjusted LYs (QALYs), and lifetime costs were estimated. One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. RESULTS: ABCP provided an additional 0.413 QALYs (0.460 LYs) and 0.738 QALYs (0.956 LYs), respectively, compared with BCP and CP. The corresponding incremental costs were $234,998 and $381,116, respectively. The incremental cost-effectiveness ratio for ABCP was $568,967 per QALY compared with BCP and $516,114 per QALY compared with CP. The subgroup analysis demonstrated that PD-L1 expression of ≥50% on tumor cells (TC3) or ≥10% on immune cells (IC3) decreased the incremental cost-effectiveness ratio to $464,703 per QALY. CONCLUSIONS: From the perspective of the US payer, ABCP is estimated to not be cost-effective compared with BCP or CP in the first-line setting for patients with metastatic, nonsquamous NSCLC at a willingness-to-pay threshold of $100,000 per QALY. Cancer 2019;125:3526-3534.

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Section: Discussionmentioning

confidence: 99%

First‐line atezolizumab in addition to bevacizumab plus chemotherapy for metastatic, nonsquamous non–small cell lung cancer: A United States–based cost‐effectiveness analysis

Wan

Luo

Tan

et al. 2019

Cancer

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“…One hundred forty consecutive patients who were treated at Melanoma Institute Australia between December 2013 and March 2018 with combination anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab or pembrolizumab) antibodies in the first-line setting for stage IV melanoma were included. Patients were treated with different combination doses and schedules as part of a clinical trial (Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma [CheckMate-067 5 ]; Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study [ABC -Anti-PD1 Brain Collaboration Study] 12 16 ]) or were treated off trial with ipilimumab and nivolumab according to the standard, approved schedule. This project had institutional ethics review board approval, and written informed consent was obtained from each patient.…”

Section: Patients and Treatmentmentioning

confidence: 99%

Site‐specific response patterns, pseudoprogression, and acquired resistance in patients with melanoma treated with ipilimumab combined with anti–PD‐1 therapy

Silva

Quek

et al. 2019

Cancer

130

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Background Patients with metastatic melanoma have variable responses to combination ipilimumab and nivolumab. The objectives of this study were to examine the patterns of response and survival in patients treated with combination ipilimumab and anti–PD‐1 therapy (IPI + PD1) and to explore the nature of pseudoprogression and acquired resistance. Methods Patients with metastatic melanoma who received treatment with first‐line IPI + PD1 had all metastases ≥5 mm measured on computed tomography/magnetic resonance imaging studies. The lesional response rate (LRR) and the overall response rate (ORR) were determined according to Response Evaluation Criteria in Solid Tumors, version 1.1. Results In total, 140 patients who had 833 metastases were studied. The ORR and the overall complete response (CR) rate decreased as tumor burden or the number of metastases increased. Metastases that had a CR (49%) were smaller than metastases without a CR (median, 13 vs 17 mm; P < .0001). Soft‐tissue and lung metastases had the highest LRR (79% and 77%, respectively), whereas liver metastases had the lowest (46%). In multivariate analysis, patients with lung metastases had superior ORR (odds ratio [OR], 2.75; P = .02) and progression‐free survival (hazard ratio [HR], 0.46; P = .02), whereas those with liver metastases had inferior ORR (OR, 0.33; P = .02), progression‐free survival (HR, 4.03; P < .01), and overall survival (HR, 3.17; P = .01). Pseudoprogression occurred in one‐third of patients who had progressive disease as their best response, with an overall survival that was comparable to that of patients without disease progression. Acquired resistance occurred in 12% of responders after a median of 9.6 months, with an overall survival rate of 83% at 1 year from progression. Conclusions Metastases in different anatomical locations display distinct response patterns and also are associated with overall response and survival with combination immunotherapy. Specific sites of disease may hold unique mechanisms of resistance and should allow for more personalized treatment.

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“…Based on current labeling for the treatment of melanoma patients, ipilimumab and nivolumab are administered together only for the initial four doses; nivolumab is then given as monotherapy [12]. Alternative dosing regimens for ICBs used in combination are currently under investigation, with the goal of improving the safety profile while maximizing clinical benefit [125,142,143].…”

Section: Immunotherapy-based Combination Approachesmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function through modulation of the immune system, which can lead to immune-mediated adverse events (imAEs). These include a range of dermatologic, gastrointestinal, endocrine, and hepatic toxicities, as well as other less common inflammatory events. ImAEs are typically low grade and manageable when identified early and treated with appropriate measures. Identifying the right patient for the right therapy will become more important as new immunotherapies and immunotherapy-based combinations are approved and costs of cancer care continue to rise.

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Standard-dose pembrolizumab in combination with reduced-dose ipilimumab for patients with advanced melanoma (KEYNOTE-029): an open-label, phase 1b trial

Cited by 222 publications

References 27 publications

First‐line atezolizumab in addition to bevacizumab plus chemotherapy for metastatic, nonsquamous non–small cell lung cancer: A United States–based cost‐effectiveness analysis

First‐line atezolizumab in addition to bevacizumab plus chemotherapy for metastatic, nonsquamous non–small cell lung cancer: A United States–based cost‐effectiveness analysis

Site‐specific response patterns, pseudoprogression, and acquired resistance in patients with melanoma treated with ipilimumab combined with anti–PD‐1 therapy

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

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