Immune Checkpoint Inhibitors Articles


  • A Potential Mechanism of Anticancer Immune Response Coincident With Immune-related Adverse Events in Patients With Renal Cell Carcinoma.

    Some reports showed encouraging efficacy of immune checkpoint inhibitors among patients who experienced immune-related adverse events (irAEs). Thus, characterization of T-cell repertoire and immune signatures in peripheral blood mononuclear cells (PBMCs) and tumors before and after immune checkpoint inhibitors treatment should contribute to better understanding of irAE-provoked anticancer immune responses.

    Published September 9, 2020
  • ATM Mutations Benefit Bladder Cancer Patients Treated With Immune Checkpoint Inhibitors by Acting on the Tumor Immune Microenvironment.

    Immune checkpoint inhibitors (ICIs) have shown promising results in bladder cancer (BC). However, only some patients respond to ICIs. DNA repair defects (DDR) play an important role in the therapeutic response of bladder cancer.

    Published September 17, 2020
  • Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response.

    Radiotherapy (RT), as part of trimodal therapy, is an attractive alternative treatment in patients with urothelial muscle-invasive bladder cancer (MIBC). There is accumulating evidence suggesting the immunomodulatory effects of RT and its potential synergy when combined with immunotherapy.

    Published September 16, 2020
  • Combining Immune Checkpoint and VEGFR Inhibition in Favorable Risk and Elderly Patients With Metastatic Renal Cell Carcinoma.

    Immune checkpoint inhibitors and vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors are the most commonly used medications in metastatic renal cell carcinoma (mRCC). Recently, large clinical trials have shown favorable outcomes in patients treated with combined immune checkpoint plus VEGFR inhibition compared with VEGFR inhibition alone.

    Published March 20, 2020
  • Complete response of renal cell carcinoma with an inferior vena cava tumor thrombus and lung metastases after treatment with nivolumab plus ipilimumab.

    In recent years, immune checkpoint inhibitors have become the most important drugs for treating renal cell carcinoma. In combination with performing nephrectomies, tyrosine kinase inhibitors have been used as neoadjuvant therapy, as they reduce the size of a primary renal mass and cause the disappearance of metastatic lesions.

    Published April 13, 2020
  • Emerging Role of Immunotherapy in Advanced Urothelial Carcinoma.

    Advanced urothelial carcinoma (aUC) has long been treated preferably with cisplatin-based chemotherapy, but many patients are cisplatin-ineligible whereas for those who progress on a platinum-based regimen treatment options are limited.

    Published April 23, 2018
  • Establishing guidelines to harmonize tumor mutational burden (TMB): in silico assessment of variation in TMB quantification across diagnostic platforms: phase I of the Friends of Cancer Research TMB Harmonization Project.

    Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase of interrogated genomic sequence, demonstrates predictive biomarker potential for the identification of patients with cancer most likely to respond to immune checkpoint inhibitors.

    Published April 17, 2020
  • Frontline immunotherapy treatment with nivolumab and ipilimumab in metastatic renal cell cancer: a new standard of care.

    Nivolumab is a programmed death 1 (PD-1) inhibitor currently approved as second-line treatment for advanced renal cell carcinomas (RCC) after failure of standard antiangiogenic treatment. Motzer et al.

    Published October 22, 2018
  • Genomic Analysis of Tumor Microenvironment Immune Types across 14 Solid Cancer Types: Immunotherapeutic Implications.

    We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy.

    Published September 19, 2017
  • Immune Checkpoint Inhibition and the Prevalence of Autoimmune Disorders Among Patients With Lung and Renal Cancer.

    Immune checkpoint inhibition reactivates the immune response against cancer cells in multiple tissue types and has been shown to induce durable responses. However, for patients with autoimmune disorders, their conditions can worsen with this reactivation.

    Published June 22, 2017
  • Immune Checkpoint Inhibitors and Prostate Cancer: A New Frontier?

    Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC), agents that provide durable disease control and long-term survival are still needed. It is a fact that a tumor-induced immunosuppressive status (mediated by aberrant activation of inhibitory immune checkpoint pathways as a mechanism to evade host immune surveillance) plays a crucial role in the pathogenesis of cancer, including prostate cancer (PC), making CRPC patients suitable candidates for immunotherapy.

    Published August 3, 2016
  • Immune checkpoint inhibitors in advanced renal cell carcinoma: experience to date and future directions.

    In recent years, there has been dramatic expansion of the treatment armamentarium for patients with advanced renal cell carcinoma (aRCC), including drugs targeting vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways.

    Published April 10, 2017
  • Immune-checkpoint inhibitors in melanoma and kidney cancer: from sequencing to rational selection.

    Immune-checkpoint inhibitors (ICPIs), including antibodies against cytotoxic T-lymphocyte associated antigen 4 and programmed cell death protein 1, have been shown to induce durable complete responses in a proportion of patients in the first-line and refractory setting in advanced melanoma and renal cell carcinoma.

    Published July 9, 2018
  • Immunotherapy advances in uro-genital malignancies.

    Immunotherapy for the treatment of cancer has made significant progresses over the last 20 years. Multiple efforts have been attempted to restore immune-mediated tumor elimination, leading to the development of several targeted immunotherapies.

    Published July 4, 2016
  • Immunotherapy Is Changing First-Line Treatment of Metastatic Renal-Cell Carcinoma.

    The incidence of renal-cell carcinoma has been increasing each year, with nearly one third of new cases diagnosed at advanced or metastatic stage. The advent of targeted therapies for metastatic renal-cell carcinoma (mRCC) has underscored the need to subtype tumors according to tumor-immune expression profiles that may more reliably predict treatment outcomes.

    Published March 14, 2019
  • Immunotherapy versus standard of care in metastatic renal cell carcinoma. A systematic review and meta-analysis.

    Recently, immune checkpoint inhibitors against PD-1/PD-L1 or CTLA4 have emerged as new treatments for metastatic renal cell carcinoma (mRCC), despite discrepancy between their effects on OS and PFS.

    Published September 6, 2018
  • Immunotherapy: a glimmer of hope for metastatic prostate cancer.

    Prostate cancer was the first cancer in which immunotherapy vaccine was approved by FDA in 2010 named Sipuleucel-T. No new immunotherapies have been approved since, as phase 3 trials didn't show any improvement in overall survival (OS) especially with immune checkpoint inhibitors.

    Published June 8, 2018
  • Immunotherapy: A New (and Old) Approach to Treatment of Soft Tissue and Bone Sarcomas.

    Soft tissue and bone sarcomas are a rare and heterogeneous form of cancer. With standard of care treatment options including surgery, radiation, and chemotherapy, the long-term survival is still low for high-risk soft tissue sarcoma patients.

    Published September 29, 2017
  • Immunotherapy: last bullet in platinum refractory germ cell testicular cancer.

    Testicular germ cell tumors are chemosensitive with very high cure-rates even in the metastatic setting. However, patients with platinum-refractory and relapsing tumors after autologous stem cell transplant have very poor outcomes despite salvage treatments, and with no effective alternative therapies.

    Published February 25, 2019
  • Improving IMDC Prognostic Prediction Through Evaluation of Initial Site of Metastasis in Patients With Metastatic Renal Cell Carcinoma.

    Several models are adopted in clinical practice to estimate prognosis of patients with metastatic renal cell carcinoma (mRCC); however, none of these models have evaluated patients treated by immune-checkpoint inhibitors.

    Published November 26, 2019
  • Management of metastatic bladder cancer.

    Important advances in the understanding of the biology and mechanisms of tumor progression of urothelial carcinoma (UC) have been achieved over the past decade. The treatment landscape for advanced-stage, unresectable or metastatic UC has shifted dramatically over a short period of time, with 6 new therapeutic agents available for clinical use.

    Published April 30, 2019
  • Myasthenia gravis: An emerging toxicity of immune checkpoint inhibitors.

    The advent of immunotherapy has heralded a number of significant advances in the treatment of particular malignancies associated with poor prognosis (melanoma, non-small-cell lung, renal and head/neck cancers).

    Published July 5, 2017
  • Neoadjuvant Chemotherapy or Immunotherapy for Clinical T2N0 Muscle-invasive Bladder Cancer: Time to Change the Paradigm?

    A 41-yr-old, otherwise healthy, premenopausal woman presented at our uro-oncology clinic with a diagnosis of muscle-invasive bladder cancer following a transurethral resection of the bladder performed at another center.

    Published August 31, 2020
  • Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis.

    Nivolumab alone and in combination with ipilimumab is approved for the treatment of patients with metastatic renal cell carcinoma (RCC) who received prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) and those who are treatment naive, respectively.

    Published March 23, 2020
  • Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis.

    Nivolumab alone and in combination with ipilimumab is approved for the treatment of patients with metastatic renal cell carcinoma (RCC) who received prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) and those who are treatment naive, respectively.

    Published September 12, 2019
  • Novel immunotherapy in metastatic renal cell carcinoma.

    Despite the rapid development of therapeutic modalities for metastatic renal cell carcinoma (mRCC) over the past decade to include a number of targeted antiangiogenic therapies and traditional immunotherapy, such as high-dose interleukin-2 and interferon-α, mRCC continues to be associated with poor prognosis.

    Published July 13, 2017
  • Overview and management of toxicities associated with systemic therapies for advanced renal cell carcinoma.

    The advent of novel targeted agents for metastatic renal cell carcinoma (RCC) has offered clinical benefits over traditional immunotherapy (e.g., interleukin-2 and interferon-α) in both efficacy and safety profiles.

    Published September 21, 2015
  • Rational Approaches to Treatment Duration with Immunotherapy in Metastatic Renal Cell Carcinoma.

    Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm for metastatic renal cell carcinoma. The appropriate duration for ICI treatment is not clear, however. Analyses of landmark trials reveal that some patients exhibit sustained durable responses to ICIs even after treatment discontinuation, resulting in prolonged treatment-free intervals that can mitigate potential toxicities and the considerable financial burden associated with treatment.

    Published November 28, 2019
  • Recent developments in small molecule therapies for renal cell carcinoma.

    Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and is known to be the 10th most common type of cancer in the world. Most of the currently available RCC drugs are tyrosine kinase inhibitors (TKIs).

    Published August 31, 2017
  • Renal Toxicity of Systemic Therapy for Renal Cell Carcinoma.

    The incidence of kidney cancer has been increasing steadily and, until recently, there was a substantial lack of effective therapies for a cancer that is now among the 10 most common cancers in men and women.

    Published March 12, 2020
  • Response Rate to Chemotherapy After Immune Checkpoint Inhibition in Metastatic Urothelial Cancer.

    Immune checkpoint inhibitors (ICIs) are active in metastatic urothelial carcinoma (MUC). They have joined chemotherapy (CT) as a standard of care. Here, we investigate the activity of CT after progression on ICIs.

    Published October 4, 2017
  • Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma.

    Immune checkpoint inhibitors (ICI) induce a range of immune-related adverse events (irAEs) with various degrees of severity. While clinical experience with ICI retreatment following clinically significant irAEs is growing, the safety and efficacy are not yet well characterized.

    Published March 6, 2020
  • SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018).

    The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics.

    Published January 9, 2019
  • Sequencing of PD-1/L1 Inhibitors and Carboplatin-Based Chemotherapy for Cisplatin-Ineligible Metastatic Urothelial Carcinoma.

    Current first-line treatment options in patients with metastatic urothelial carcinoma (mUC) unfit to receive cisplatin-containing chemotherapy include PD-1/L1 inhibitors and carboplatin-containing chemotherapy.

    Published September 18, 2020
  • State of the Future: Translational Approaches in Renal Cell Carcinoma in the Immunotherapy Era.

    The emergence of immune checkpoint inhibitors as treatment options for metastatic renal cell carcinoma (RCC) has significantly improved outcomes for patients, but also posed new challenges for researchers.

    Published March 6, 2019
  • Supportive care for patients undergoing immunotherapy.

    Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents.

    Published July 17, 2017
  • Systematic Review of Immune Checkpoint Inhibition in Urological Cancers: Beyond the Abstract

    Traditionally, the systemic treatment of advanced and metastatic urothelial cell cancer (UCC), renal cell carcinoma (RCC), and prostate cancer (PC) consists of chemotherapy, targeted therapy, and androgen deprivation therapy, respectively. Although these treatment modalities have improved patient outcome, most patients will eventually experience progressive disease. Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are able to reactivate the immune system against tumor cells by targeting PD-1/L1 and CTLA-4 signaling. These agents have shown efficacy in the treatment of a variety of solid tumors and may provide a novel treatment strategy for patients with advanced and metastatic urological cancers. In this systematic review, 22 phase 1–3 clinical trials were identified. Six randomized clinical trials (RCT) were discussed in detail (one trial on UCC, three trials on RCC, and two trials on PC) to study the efficacy and safety of ICIs in urological cancers.
    Published July 17, 2017
  • Systematic Review of Immune Checkpoint Inhibition in Urological Cancers.

    In patients with advanced and metastatic urological cancers, clinical outcome may be improved by immune checkpoint inhibitors (ICIs).

    To systematically review relevant literature on efficacy and safety of ICIs in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer.

    Published June 26, 2017
  • Systemic therapy for metastatic renal cell carcinoma in the first-line setting: a systematic review and network meta-analysis.

    Management of metastatic renal cell cancer (mRCC) has undergone a paradigm shift with immune-checkpoint inhibitors (ICI) in the first-line setting. However, direct comparative data are inadequate to inform treatment decisions.

    Published August 13, 2020
  • The Changing Therapeutic Landscape of Metastatic Renal Cancer.

    The practising clinician treating a patient with metastatic clear cell renal cell carcinoma (CCRCC) faces a difficult task of choosing the most appropriate therapeutic regimen in a rapidly developing field with recommendations derived from clinical trials.

    Published August 28, 2019
  • The Feasibility and Safety of Surgery in Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Study.

    Immune checkpoint inhibitors (ICI) are revolutionizing care for cancer patients. The list of malignancies for which the Food and Drug Administration is granting approval is rapidly increasing. Furthermore, there is a concomitant increase in clinical trials incorporating ICI.

    Published July 5, 2017
  • The immunotherapy revolution in genitourinary malignancies.

    Immune checkpoint inhibitor (ICI) therapy and therapeutic cancer vaccines have continued to demonstrate survival benefit and durable clinical response in patients with renal cell cancer, prostate cancer and bladder cancer, with limited responses in testicular cancer.

    Published July 7, 2020
  • The Interplay between Inflammation, Anti-Angiogenic Agents, and Immune Checkpoint Inhibitors: Perspectives for Renal Cell Cancer Treatment.

    Treatment options for metastatic renal cell carcinoma (RCC) have been expanding in the last years, from the consolidation of several anti-angiogenic agents to the approval of immune checkpoint inhibitors (ICIs).

    Published December 26, 2019
  • The Performance Status and Response to Immune Checkpoint Inhibition in Patients with Advanced Urothelial Carcinoma - Ali Khaki

    Ali Khaki joins Petros Grivas in a discussion on the performance status and response to immune checkpoint inhibition in patients with advanced urothelial cancer. These checkpoint inhibitors have changed the landscape of treatment for urothelial cancer and there has been more and more interest in using them in people who are not suitable for chemotherapy, as approved in the post-platinum setting, and for more vulnerable patients.


    Ali Khaki, MD, Hematology/Oncology Fellow, Fred Hutchison Cancer Research Center, University of Washington, Seattle, Washington, United States

    Petros Grivas, MD, Ph.D., Clinical Director, Genitourinary Cancers Program, University of Washington Medicine Associate Professor, Department of Medicine, Division of Oncology, University of Washington School of Medicine

    Read the Full Video Transcript

    Petros Grivas: Hello, I'm Petros Grivas, I'm an Associate Professor of Medicine at the University of Washington and Fred Hutchinson Cancer Research Center, and Medical Oncologist at the Seattle Cancer Care Alliance. I'm very fortunate today to be accompanied in this beautiful environment at ASCO by Dr. Ali Khaki. Ali is a superstar Fellow at the University of Washington, and he is doing great work in the field. Ali, welcome.

    Ali Khaki: Thank you Petros, it's good to be here. Thank you for inviting me.

    Petros Grivas: So, it's really exciting to be in a form like ASCO with so many datasets and findings that potentially can change the way we treat cancer down the road. I would like to focus our discussion specifically on the work you are presenting, with this very interesting poster looking at the performance status and response to immune checkpoint inhibition in patients with advanced urothelial cancer.

    Ali Khaki: Yeah. Something that drew my interest is that as these checkpoint inhibitors have changed the landscape of treatment for urothelial cancer, there's been more and more interest in using them in people who are not suitable for chemotherapy, as approved in the post-platinum setting, and for more vulnerable patients.

    Early literature has shown that up to a third of patients with poor performance status may be getting these treatments, but the clinical trials did not include these patients. Only three of the eight trials had ECOG Performance Status of two, and no one had ECOG Performance Status worse than that. So I wanted to look further into, what are the outcomes in the real world for these sort of patients? So what we were able to do is we were able to get together 15 institutions to do a multi-institution chart review. We did a retrospective chart review of up to 400 patients, 402 patients total, and got data about their clinical history leading up to the checkpoint inhibitor use, as well as their outcomes on treatment.

    Petros Grivas: Interesting.

    Ali Khaki: In that cohort, we had complete data to be done for the analysis in 369 of those patients. About 52% were treated with first-line checkpoint inhibitors in the metastatic setting, and 48% were treated in the second-line or beyond in the salvage setting.

    Petros Grivas: So it has half and half in the two, first and second line.

    Ali Khaki: Yeah. In the majority of patients either got atezolizumab or pembrolizumab with a scattering of some of the other checkpoint inhibitors that are approved in that setting.

    Petros Grivas: And those who got salvage therapy are maybe second line and beyond, right?

    Ali Khaki: Correct. So the two things we want to look for in terms of clinical outcomes are the response rate, as well as survival. And while we didn't see any differences in response rate, or we saw numerical differences but they were not statistically significant. So in the first line, it was 28% for those with good performance status, and 24% for those with poor performance status. And in the second line, salvage setting, it was 25% compared to 20%. Again, slightly higher, but not statistically significant.

    What we did see, is we did see in the first line patients did have worse survival if you did have a poor performance status. So checkpoint inhibitor therapy is not necessarily salvaging our vulnerable patients and helping them live as long as patients with good performance status. That's my major take-home from that first part of the analysis.

    Petros Grivas: Interesting. So it sounds like if you have a patient with a very poor performance status, let's say an ECOG PS of three, in your opinion, it's unlikely to change the trajectory of disease by using checkpoint inhibition.

    Ali Khaki: Exactly.

    Petros Grivas: And it's hard, of course, to predict what will happen with the individual patient, but it's informing your decision-making process, it sounds like.

    Ali Khaki: Exactly, yeah. So it would have been very helpful if we saw that the response rate was worse. From that perspective, we could help guide who should not get treatment, in the same way that we don't give chemotherapy to patients who have poor performance status. We don't have that strong of evidence from that perspective for this population, and that underscores the need for more and more biomarker work or other sorts of prognostic tools to be developed to help guide clinicians in that decision-making process.

    Petros Grivas: Do you think that either worse survival vs. the response rate, either or both are relevant in the context of this discussion, especially with all the confounding factors for those patients?

    Ali Khaki: Right, yeah. I mean I think that they are both relevant. I think that it helps guide that conversation. I think it's a much more nuanced conversation now. And so if you have a patient for example who is young and is very very motivated, even with poor performance status is might be someone who you're like, “Okay this is still something worth trying.” But having that sort of measured discussion of, “The outcomes aren't necessarily as great for you if you're pretty unfit moving into this.” But if you have an older patient who is pretty vulnerable already, and is not up for continued hospitalizations or continued treatment of any sort, this might be the time where you use this information to guide that patient to moving towards hospice at an earlier time.

    Petros Grivas: So, like everything we do it's some incremental knowledge and information that can help inform some individual discussion with the patient. Of course, it cannot be definitive or conclusive for each individual patient, but it can definitely help this informed discussion that can happen.

    Ali Khaki: Exactly.

    Petros Grivas: Do you want to talk a little bit about the end-of-life healthcare utilization, cost of care, and what are the findings from the study in that regard?

    Ali Khaki: The comments I'm making about the difference between the older and younger patients are informed by that second half of our analysis. And so the next thing we did is we looked at utilization patterns for patients who died in the study. So about 215 of our patients were deceased at the time of data collection, and we actually had the site of death being hospital vs. not hospital for 140 of those patients.

    So we asked the question of, how many of those patients who died were treated in the last 30 days; in the last 90 days of life? And what we saw is about 10% in both the 215 population and the 140 population were treated in the last 30 days of life, and about 35% were treated in the last 90 days of life. And when I'm saying treated, I mean the new initiation of treatment. And so we're looking at starting this new line of therapy in the last 30 or 90 days of life. What we saw is that for those patients who died... we know the site of death, so that 140 patient population, there was an increased odds of you dying in the hospital if you had initiation in the last 30 days of life. That was statistically significant. So it suggests to that point I was making about, if you're doing this you might end up having a more aggressive death. You may not be at home with your friends and family in a peaceful way. It's just a small signal but sheds some light onto what those patients' experiences may be.

    And the other thing I was interested in, as the cost is becoming a bigger and bigger part of our healthcare system, is estimating how much are we spending on checkpoint inhibitors for these patients who are dying soon thereafter starting on this treatment. So, we estimated that using basically the average wholesale price, which is one of a number of different ways you could estimate this. So we got that published value and calculated what that cost would be per patient based off the type of treatment they got, being whichever medication they got, and how many cycles they received that last 30 or 90 days of life. We estimated that $1400 were spent per patient in the last 30 days of life, for these patients who were new initiations, and $2800 was spent for people who were treated in the 90 days, with a new initiation in the last 90 days of life.

    Petros Grivas: That's very very informative, and I think it's very, I would say, insightful data because cost-effectiveness and value-based care is an everyday topic of discussion. And having this, even early data I would say can definitely be informative and very interesting to take into account when you have a patient in front of you, you want to do the best for the patient. And that takes into account, of course, the cost and expectations this patient has. But having it in your mind some context about the healthcare utilization and cost I think are important, especially healthcare systems that may not sustain significant cost and an unfavorable cost to value ratio.

    Ali Khaki: Exactly. And if we are able to identify biomarkers or prognostic tools that help identify who is or is not going to benefit, this would really help underscore that reason of deciding not to treat people who are not going to benefit all the more.

    Petros Grivas: And that's important, and goes back to the urgent need for predictive markers that can actually help tease out which patients may benefit more from others. And in that current era, we need more biomarkers with proven clinical utility, prospective validated, especially in the context of this data.

    Ali Khaki: Exactly, yeah.

    Petros Grivas: And of course, in addition to the cost of drug acquisition right, to buy as a practice, a particular chemotherapy, immunotherapy agent, it is also the cost of managing side-effects. We did some work before regarding evaluation of the cost estimates for managing side-effects from chemotherapy and immunotherapy in patients in the first line suffering from advanced urothelial cancer, and we found some interesting results, I don't know if you've had the chance to take a look at that.

    Ali Khaki: Yeah, I don't know if I have the exact numbers, but it was very insightful to see. We often talk about how beneficial checkpoint inhibitors are, and how well-tolerated they are, but I think we under-appreciate the toxicity, especially the immune-related adverse events that lead to hospitalizations and IV treatments, or even sometimes initial procedures to get diagnosis. And I think that you showed in particular toxicity, like pneumonitis and colitis, what was the extent of the cost, again with an estimate based off the in-patient hospitalization time, and some of these other costs that were associated with that. Which is very useful information because again I think the rhetoric and the narrative around these medications is how great they are, but we have to have a more measured perspective on what we're dealing with here.

    Petros Grivas: And we definitely need this data, both for chemotherapy and immunotherapy as you mentioned, and we saw corresponding costs for chemotherapy-related adverse events: dehydration, acute kidney injury, infection, sepsis, and so forth, and immunotherapy. So having these data are important because it can inform decisions among multiple stake-holders, how we are going to develop trials and prospective data to inform our decisions and share those data with those stake-holders and the patients because I think it's relevant to our clinical practice. So moving on overall in your, I would say estimate, about next steps in the field of outcomes research, value-based care, cost-effectiveness, how do you envision that the field will move forward? How do you see the research in this particular field evolve, especially with the discussion of choose wisely, select wisely from ASCO, and other value-based care prepositions?

    Ali Khaki: I think there's a few different things that are interesting. One is identifying those low-value practices, that's what choosing wisely does. That's what some of the attempts of my work here was to do, is to look at things that if we know that they clearly are not benefiting patients, we can help guide clinicians and the practice of medicine away from those practices. So I think that's one major point of it. Another big thing is how are we paying for things in general? And so I've been doing some work trying to compare the multi-insurance healthcare system in the US to the single-payer system in Canada, trying to quantify what are the differences in cost. Again, I have a lot of interest in end-of-life care patients and the different markers of utilization in that patient population, it's very vulnerable.

    Petros Grivas: Interesting. So, because I know it's your personal interest, do you see this field growing in the future and across tumor types?

    Ali Khaki: I think so, I think that healthcare is a growing cost for everyone, not only for those who are sick but also for those who are well, as it becomes a larger portion of our GDP for one thing. And then at our institution, there's been other faculty who have reported extensively about the financial toxicity of a cancer diagnosis specifically, leading to increased risks of bankruptcy, and the harms both in terms of treatment adherence, as well as personal stress and burden that it's all associated with. And so I think that as we better understand the larger harms, the larger toxicity that our treatment has on patients, it's imperative that we begin to develop new ways of understanding this, and then hopefully finding ways so we can curb these practices.

    Petros Grivas: Absolutely, I fully agree with you. And there is great work being done by Dr. Shankaran that you mentioned, Dr. Lampe and Dr. Cooper in that regard. And I think having these discussions in an open and transparent way is very very critical. Quality of care, outcomes, research, value-based care, sometimes may not be the first thing that we think in the clinic, but overall as a healthcare system are important cost durations. And having research tools to measure those metrics can go a long way.

    Ali Khaki: And if I see a patient in my clinic and I tell them, “I want you to live longer and I want you to live better.” But I put them into bankruptcy, I don't think that's making them live better by any means. And so I think that we have to consider that we may help people live longer, but if we're leaving them in a life debilitated by bankruptcy, then that's not a quality of life that we want to leave them with.

    Petros Grivas: You introduce a new term, called financial toxicity, which is important and cannot be neglected, and has to go with access to care. Many patients may not be able to have access to care. And of course, the healthcare disparities issue is an important component of research, and of course of consideration on how we can move the field forward and improve outcomes on the global level.

    Ali Khaki: Yeah. And I'm excited both that ASCO as well as the work that's being done at the HICOR Institute, as part of the Fred Hutch, to help begin to move that forward. Both in terms of financial disparities but also race disparities, geographic disparities, these are all important things that we hopefully better understand and make increased access for all our patients in terms of standard-of-care treatments, as well as clinical trials.

    Petros Grivas: I fully agree with you, and the work being done in the Fred Hutchinson Cancer Research Center, University of Washington, and Seattle Cancer Care Alliance as a clinical cancer center I think is very relevant in that direction, and we need more people like you who have this interest and focus. Hopefully, we will have the opportunity to talk more about that in the near future.

    Ali Khaki: Thank you, yeah. It's been a pleasure, it's an exciting area of work to go into because I feel like it has such potential to really change patient care, but also change the state of our society and the cost that we're all enduring, so I'm excited to keep working in this field.

    Petros Grivas: And collaborate with many other leaders in the field and work together.

    Ali Khaki: Exactly.

    Petros Grivas: Ali, thank you so much for coming here today and spending time with us, and I would like to also thank the audience for their attention.

    Ali Khaki: Thank you so much.
    Published December 13, 2019
  • The tumour microenvironment and metabolism in renal cell carcinoma targeted or immune therapy.

    Renal cell carcinoma (RCC) is one of the most common tumours of the urinary system, and is insidious and not susceptible to chemoradiotherapy. As the most common subtype of RCC (70-80% of cases), clear cell renal cell carcinoma (ccRCC) is characterized by the loss of von Hippel-Lindau and the accumulation of robust lipid and glycogen.

    Published August 26, 2020
  • Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review.

    Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) produce unique toxicity profiles.

    Published October 5, 2017
  • Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma.

    Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma.

    Published June 5, 2019