Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement

Tsimberidou, Apostolia M.; Levit, Laura; Schilsky, Richard L.; Averbuch, Steven D.; Chen, Daniel; Kirkwood, John M.; McShane, Lisa M.; Sharon, Elad; Mileham, Kathryn F.; Postow, Michael A.

doi:10.1186/s40425-018-0426-7

Cited by 20 publications

(17 citation statements)

References 46 publications

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“…These collaborative efforts have already successfully led to CIT-specific assessment of response, publication guidelines, adverse event management and diagnostic approaches (Haanen et al, 2017;Hodi et al, 2018a;Tsimberidou et al, 2018). However, as the field has grown over the past several years, so has the number of different efforts that seek to bring different components of cancer research together.…”

Section: Discussionmentioning

confidence: 99%

Top 10 Challenges in Cancer Immunotherapy

Hegde¹,

2020

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Cancer immunotherapy is a validated and critically important approach for treating patients with cancer. Given the vast research and clinical investigation efforts dedicated to advancing both endogenous and synthetic immunotherapy approaches, there is a need to focus on crucial questions and define roadblocks to the basic understanding and clinical progress. Here, we define ten key challenges facing cancer immunotherapy, which range from lack of confidence in translating pre-clinical findings to identifying optimal combinations of immune-based therapies for any given patient. Addressing these challenges will require the combined efforts of basic researchers and clinicians, and the focusing of resources to accelerate understanding of the complex interactions between cancer and the immune system and the development of improved treatment options for patients with cancer.

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Section: Discussionmentioning

confidence: 99%

Top 10 Challenges in Cancer Immunotherapy

Hegde¹,

2020

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“…The addition of surrogate endpoints or further emphasis on clinical endpoints already reported including ORR may prove useful in future evaluations. Recommendations for reporting clinical trials to address unique efficacy, toxicity and combination and sequencing aspects of immuno-oncology have been reported by the Trial Reporting in I-O (TRIO) guidance 46 .…”

Section: Discussionmentioning

confidence: 99%

Cohort versus patient level simulation for the economic evaluation of single versus combination immuno-oncology therapies in metastatic melanoma

Gibson¹,

Begum²,

Koblbauer³

et al. 2019

Journal of Medical Economics

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Background: Model structure, despite being a key source of uncertainty in economic evaluations, is often not treated as a priority for model development. In oncology, partitioned survival models (PSMs) and Markov models, both types of cohort model, are commonly used, but patient responses to newer immuno-oncology (I-O) agents suggest that more innovative model frameworks should be explored. Objective: A discussion of the theoretical pros and cons of cohort level vs patient level simulation (PLS) models provides the background for an illustrative comparison of I-O therapies, namely nivolumab/ipilimumab combination and ipilimumab alone using patient level data from the CheckMate 067 trial in metastatic melanoma. PSM, Markov, and PLS models were compared on the basis of coherence with short-term clinical trial endpoints and long-term cost per QALY outcomes reported. Methods: The PSM was based on Kaplan-Meier curves from CheckMate 067 with 3-year data on progression free survival (PFS) and overall survival (OS). The Markov model used time independent transition probabilities based on the average trajectory of PFS and OS over the trial period. The PLS model was developed based on baseline characteristics hypothesized to be associated with disease as well as significant mortality and disease progression risk factors identified through a proportional hazards model. Results: The short-term Markov model outputs matched the 1-3 year clinical trial results approximately as well as the PSMs for OS but not PFS. The fixed (average) cohort PLS results corresponded as well as the PSMs for OS in the combination therapy arm and PFS in the monotherapy arm. Over the lifetime horizon, the PLS produced an additional 5.95 quality adjusted life years (QALYs) associated with combination therapy relative to ipilimumab alone, resulting in an incremental cost-effectiveness ratio (ICER) of £6,474 per QALY, compared with £14,194 for the PSMs which gave an incremental benefit of between 2.2 and 2.4 QALYs. The Markov model was an outlier ($ £49,000 per QALY in the base case). Conclusions: The 4-and 5-state versions of the PSM cohort model estimated in this study deviate from the standard 3-state approach to better capture I-O response patterns. Markov and PLS approaches, by modeling state transitions explicitly, could be more informative in understanding I-O immune response, the PLS particularly so by reflecting heterogeneity in treatment response. However, both require a number of assumptions to capture the immune response effectively. Better I-O representation with surrogate endpoints in future clinical trials could yield greater model validity across all models. ARTICLE HISTORY

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“…Secondary endpoints were safety, treatment compliance, PFS during SCAI and LCBI, defined as the time from the start of SCAI or LCBI until disease progression or death due to any cause, OS since SCAI, defined as the time from the start of SCAI until death from any cause, and OS since the first line of treatment, defined as the time from the start of first-line therapy until death from any cause. Efficacy results are presented using different plots (waterfall plots, spider plots and swimmer plots) to better report the kinetics of response, as stated in the Trial Reporting in Immuno-Oncology (TRIO) guidelines [27]. Adverse events (AEs) were recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.…”

Section: Study Design and Patientsmentioning

confidence: 99%

Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer

et al. 2021

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Background. There are still few data on the activity and safety of cetuximab-based salvage chemotherapy after immunotherapy (SCAI) in patients with squamous cell cancer of the head and neck (SCCHN). Materials and Methods. Retrospective study of patients with SCCHN who received cetuximab-based SCAI after PD1 or PDL1 (PD(L)1) inhibitors. Overall response rate (ORR) and disease control rate (DCR) with SCAI and with last chemotherapy before immunotherapy (LCBI) by RECIST 1.1, percentage change from baseline in target lesions (PCTL), progression-free survival (PFS), overall survival (OS), treatment compliance and toxicity were evaluated. Results. Between March 2016 and November 2019, 23 patients were identified. SCAI consisted of cetuximabbased combinations (3wkCDDP-5FU-Cetuximab (n=2), wkPaclitaxel-Cetuximab (n=17), wkCDDP-Cetuximab (n=2), wkCBDCA-Paclitaxel-Cetuximab (n=2)). ORR was 56.5% (11 partial response (PR), 2 complete response (CR)). DCR was 78.3%. Among 13 objective responders, median best PCTL was-53.5% (range:-30% to-100%). Median OS and PFS were 12m and 6m, respectively. In 10 patients receiving LCBI, ORR to LCBI was 40%, while ORR to SCAI achieved 60%. In LCBI-treated patients median PFS with LCBI was 8m and median PFS and OS with SCAI were 7m and 12m, respectively. Reduced dose intensity of the chemotherapy and cetuximab components occurred in 82.6% and 52.2% of the patients. Grade 1 or 2 AEs occurred in all patients. Grade 3 or 4 AEs developed in 65%, being grade 3 in all of them except in one patient (grade 4 neutropenia). There were no treatment-related deaths. Conclusion. Cetuximab-based salvage chemotherapy after PD(L)1 inhibitors associated with high response rates and deep tumor reductions with a manageable safety profile. Subsequent lines of therapy may explain the long survival achieved in our series. These results invite to design studies to elucidate the best therapeutic sequence in patients with SCCHN in the immunotherapy era. The Oncologist 2021;9999:• • Implications for Practice: Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with R/M SCCHN after progression to PD1/PDL1 inhibitors. Objective response rate was higher and progression-free survival was comparable to that of chemotherapy administered before immunotherapy (IO). In most patients, SCAI consisted of weekly, welltolerated regimens. These observations have implications for current practice due to the limited evidence to date in SCCHN and the scant therapeutic options in this disease, and invite to elucidate which may be the best treatment sequence for head and neck cancer patients in the IO era.

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Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement

Cited by 20 publications

References 46 publications

Top 10 Challenges in Cancer Immunotherapy

Top 10 Challenges in Cancer Immunotherapy

Cohort versus patient level simulation for the economic evaluation of single versus combination immuno-oncology therapies in metastatic melanoma

Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer

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