Research Highlight |
Featured
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Comment |
Value-based pricing of drugs with multiple indications or in combinations — lessons from Europe
Legislators in the USA have been discussing reforms to reduce the high cost of brand-name drugs, which are much higher in the USA than in other industrialized countries. One solution is to actively negotiate prices based on drugs’ clinical benefits. We discuss two important complexities from such an approach: drugs that have been approved for multiple indications and as part of a combination regimen.
- Kerstin N. Vokinger
- & Aaron S. Kesselheim
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Review Article |
Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC
Immune-checkpoint inhibitors (ICIs) are now standard-of-care therapies for patients with advanced-stage non-small-cell lung cancer (NSCLC) without a targetable driver alteration. Various ICIs or combination regimens have been approved in this setting, relative to chemotherapy, although no prospective data are available comparing the various ICI-based approaches. Here, the authors provide guidance on selecting the optimal ICI-based therapy and highlight several future research directions that will probably further improve the outcomes of patients with advanced-stage NSCLC.
- Michael J. Grant
- , Roy S. Herbst
- & Sarah B. Goldberg
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Review Article |
Evolution of systemic therapy for stages I–III non-metastatic non-small-cell lung cancer
The authors of this Review present the current considerations in the treatment of patients with early-stage lung cancer, discussing the critical determination of resectability by thoracic surgical oncologists and the management of both resectable and unresectable disease with a focus on systemic therapy selection. They also address innovations in drug development, trial design and efforts to identify early-stage cancers.
- Jamie E. Chaft
- , Andreas Rimner
- & Tina Cascone
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Comment |
Registration trials in countries without access to US standards of care — pitfalls of interpretation
Data from several trials support the efficacy of first-line tyrosine-kinase inhibitors combined with immune-checkpoint inhibitors (ICIs) in metastatic renal cell carcinoma. However, whether combining these drugs is preferable to using them sequentially remains unclear. Here, we assess the implications for patients and payers of limited access to second-line ICIs in the control arms of trials.
- Garth W. Strohbehn
- & Daniel A. Goldstein
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News & Views |
First clinical proof-of-concept that FMT can overcome resistance to ICIs
An unfavourable gut bacterial composition has been shown to reduce the likelihood of clinical benefit from immune-checkpoint inhibitors (ICIs). The results of two first-in-human studies of faecal microbiota transplantation in patients with melanoma refractory to anti-PD-1 antibodies validate preclinical evidence that this approach can improve the gut microbiota and overcome resistance to ICIs; however, many questions remain.
- Arielle Elkrief
- & Bertrand Routy
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Review Article |
Immunogenicity of CAR T cells in cancer therapy
CD19-specific chimeric antigen (CAR)-modified T cells are approved for patients with advanced-stage forms of certain B cell malignancies. However, a subset of patients will have anti-CAR immune responses, leading to a lack of CAR T cell persistence and a rapid loss of any antitumour efficacy. In this Review, the authors describe the extent of anti-CAR immune responses in patients and suggest measures that could be used to better monitor for these events. Additionally, they describe novel approaches to CAR T cell therapy that might reduce the risk of such responses in the future.
- Dimitrios L. Wagner
- , Enrico Fritsche
- & Mohamed Abou-el-Enein
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News & Views |
Will allogeneic CAR T cells for CD19+ malignancies take autologous CAR T cells ‘off the shelf’?
The question of whether allogeneic chimeric antigen receptor (CAR) T cells could replace autologous CAR T cell therapy has garnered considerable interest, but limited data have been available for comparisons to date. Now, Benjamin et al. have reported their experience with allogeneic anti-CD19 CAR T cells in 21 paediatric and adult patients with acute lymphoblastic leukaemia.
- Amanda M. DiNofia
- & Stephan A. Grupp
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Review Article |
PD-L1 as a biomarker of response to immune-checkpoint inhibitors
PD-L1 expression is currently the best available biomarker for the prediction of responsiveness to immune-checkpoint inhibitors. However, several immunohistochemical assays are now approved for clinical use in various settings, despite imperfect inter-assay concordance, with important implications for pathology services and, potentially, for clinical outcomes. In this Review, the authors compare the performance of the various FDA-approved PD-L1 assays, discuss the varying implications of PD-L1 expression across different tumour types and provide guidance on possible novel approaches that might optimize the clinical utility of PD-L1 as a biomarker.
- Deborah Blythe Doroshow
- , Sheena Bhalla
- & Fred R. Hirsch
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Review Article |
Advances in the development of personalized neoantigen-based therapeutic cancer vaccines
Personalized neoantigen-based therapeutic vaccines hold promise as cancer immunotherapies. This Review provides an overview of the complex personalized neoantigen vaccine production process, vaccine-induced T cell responses and strategies to enhance these responses. Completed and ongoing clinical studies testing such vaccines are discussed, and considerations for future clinical investigation of this novel, individualized form of immunotherapy are outlined.
- Eryn Blass
- & Patrick A. Ott
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Review Article |
Targeting cancer-promoting inflammation — have anti-inflammatory therapies come of age?
Chronic inflammation can promote the development of various cancers. In this Review, the current clinical advances in ameliorating inflammation for the prevention or treatment of cancer are highlighted, and the experimental insights into the biological mechanisms supporting current and potential novel anti-inflammatory approaches to the management of cancer are discussed.
- Jiajie Hou
- , Michael Karin
- & Beicheng Sun
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News & Views |
CDK4/6 inhibitors for HR+HER2− early stage breast cancer — when to escalate treatment?
Opposing results of the monarchE and PALLAS trials investigating the role of adjuvant treatment with the CDK4/6 inhibitors abemaciclib and palbociclib, respectively, in patients with hormone receptor-positive, HER2-negative early stage breast cancer have recently been presented. Herein, potential reasons why these two drugs that have similar efficacy in the metastatic setting have produced disparate results in the adjuvant setting are discussed.
- Giuseppe Curigliano
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Comment |
Consequences of COVID-19 for cancer care — a CRUK perspective
We reflect on the past 10 months of clinical activity in oncology in the UK during the COVID-19 pandemic and suggest how services can be protected during subsequent waves of infection.
- Emma Greenwood
- & Charles Swanton
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Perspective |
Artificial intelligence in radiation oncology
The possible uses of artificial intelligence (AI) in radiation oncology are diverse and wide ranging. Herein, the authors discuss the potential applications of AI at each step of the radiation oncology workflow, which might improve the efficiency and overall quality of radiation therapy for patients with cancer. The authors also describe the associated challenges and provide their perspective on how AI platforms might change the roles of radiation oncology medical professionals.
- Elizabeth Huynh
- , Ahmed Hosny
- & Raymond H. Mak
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News & Views |
SABR for metastasis-directed therapy — what we’ve learned and what’s to come
SABR-COMET was the first randomized controlled trial to demonstrate an overall survival benefit with the use of stereotactic ablative body radiotherapy (SABR) for the treatment of oligometastatic cancer. Considering the recently reported long-term follow-up data from SABR-COMET, we review the outcomes and limitations of this study in the context of other emerging information on therapy for oligometastatic disease.
- Tyler P. Robin
- & Jeffrey R. Olsen
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Review Article |
Clinical development and potential of photothermal and photodynamic therapies for cancer
Photodynamic and photothermal therapies hold promise in the local treatment of cancer although, arguably, their full potential has not yet been achieved. Herein, the authors review the current clinical progress of these phototherapies and discuss the bioengineering approaches that are being explored to overcome challenges and thereby improve such treatments.
- Xingshu Li
- , Jonathan F. Lovell
- & Xiaoyuan Chen
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Comment |
Simultaneous development of zanubrutinib in the USA and China
Zanubrutinib was recently granted expedited approval by the USA and Chinese drug regulatory authorities for the treatment of mantle cell lymphoma, thus becoming the first investigational new drug discovered in China to achieve simultaneous development in both countries. Here, we provide an overview of the regulatory processes and considerations of the two health authorities and discuss the pathways of concurrent review and approval.
- Guanqiao Li
- , Xiaozhen Liu
- & Xiaoyuan Chen
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Perspective |
Immunotherapy discontinuation — how, and when? Data from melanoma as a paradigm
The availability and subsequent successes of immune-checkpoint inhibitors (ICIs) in patients with metastatic melanoma, and to a lesser extent in those with several other forms of cancer, have made long-term treatment-free remissions a realistic possibility for a subset of patients. In this Perspective, the authors describe available data on long-term remission from patients with melanoma and other solid tumours and provide early recommendations regarding the circumstances in which ICIs can be safely discontinued.
- Caroline Robert
- , Aurelien Marabelle
- & Benjamin Besse
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Perspective |
The changing landscape of cancer in the USA — opportunities for advancing prevention and treatment
Monitoring both cancer incidence and death rates is important for guiding health policy and the direction of future research. In this Perspective, the authors describe changes in cancer incidence and death rates in the USA, highlighting the effects of specific policies and research developments, and providing insight into unmet needs that should be addressed by future health policies.
- Farhad Islami
- , Rebecca L. Siegel
- & Ahmedin Jemal
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News & Views |
Liquid biopsy for early stage lung cancer moves ever closer
Lung cancer screening is currently based only on low-dose CT scans; however, novel, more accessible methods that might improve uptake and adherence are eagerly awaited. New liquid biopsy approaches promise to revolutionize cancer screening. Herein, we discuss the opportunities and challenges associated with two such novel assays.
- Christian Rolfo
- & Alessandro Russo
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Comment |
Avoiding collateral mortality in a pandemic — time to change our mindset in surgical oncology
The coronavirus disease 19 (COVID-19) pandemic has become the focus of attention worldwide, and herein we seek to highlight the potential problem of ‘collateral mortality’ from delayed or deferred treatments in patients with cancer. We propose potential solutions to ensure continuity of care in the field of surgical oncology.
- Ker-Kan Tan
- , Brendan J. Moran
- & Michael J. Solomon
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News & Views |
Palliative care services at cancer centres — room for improvement
Evidence of quality of life improvements in patients with advanced-stage cancer has spurred a move towards early integration of palliative care into the outpatient setting. As discussed herein, meaningful and sustained improvements in timely access to palliative care requires commitments to funding, encouraging integration and routinizing referral across care settings. More palliative medicine training positions as well as broader education of clinicians and the public about the benefits of palliative care throughout the disease course are also needed.
- Jean Mathews
- & Camilla Zimmermann
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Review Article |
Progress in refining the clinical management of cancer of unknown primary in the molecular era
Despite improvements in diagnostic strategies, cancer of unknown primary — metastatic cancer in patients in whom the primary tumour remains undetected — continues to account for around 1–2% of all cancers. In this Review, Rassy and Pavlidis discuss insights into the biology of CUP and shifts in the clinical management of this enigmatic disease entity in the era of precision medicine.
- Elie Rassy
- & Nicholas Pavlidis
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