Imperial College London

Dr Mark P. Lythgoe

Faculty of MedicineDepartment of Surgery & Cancer

Clinical Research Fellow
 
 
 
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m.lythgoe

 
 
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Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

52 results found

Lythgoe MP, Sullivan R, 2022, Approved anti-PD-1 monoclonal antibodies in China: A bridge too far for US approval, European Journal of Cancer, Vol: 169, Pages: 103-105, ISSN: 0959-8049

Journal article

Benjamin DJ, Prasad V, Lythgoe MP, 2022, FDA decisions on new oncological drugs, The Lancet Oncology, Vol: 23, Pages: 585-586, ISSN: 1470-2045

Journal article

Lythgoe M, Krell J, 2022, Cancer therapy approval timings, review speed and publication of pivotal registration trials in the US and Europe from 2010-2019, Jama Network Open, ISSN: 2574-3805

Journal article

Talukder R, Makrakis D, Diamantopoulos LN, Carril-Ajuria L, Castellano D, De Kouchkovsky I, Koshkin VS, Park JJ, Alva A, Bilen MA, Stewart TF, McKay RR, Santos VS, Agarwal N, Jain J, Zakharia Y, Morales-Barrera R, Devitt ME, Grant M, Lythgoe MP, Pinato DJ, Nelson A, Hoimes CJ, Shreck E, Gartrell BA, Sankin A, Tripathi A, Zakopoulou R, Bamias A, Murgic J, Frobe A, Rodriguez-Vida A, Drakaki A, Liu S, Kumar V, Di Lorenzo G, Joshi M, Velho PI, Buznego LA, Duran I, Moses M, Barata P, Sonpavde G, Yu EY, Wright JL, Grivas P, Khaki ARet al., 2022, Response and Outcomes to Immune Checkpoint Inhibitors in Advanced Urothelial Cancer Based on Prior Intravesical Bacillus Calmette-Guerin, CLINICAL GENITOURINARY CANCER, Vol: 20, Pages: 165-175, ISSN: 1558-7673

Journal article

Jenei K, Prasad V, Lythgoe MP, 2022, High US drug prices have global implications., BMJ, Vol: 376

Journal article

Benjamin DJ, Xu A, Lythgoe MP, Prasad Vet al., 2022, Cancer drug approvals that displaced existing standard-of-care therapies, 2016-2021, Jama Network Open, Vol: 5, Pages: 1-9, ISSN: 2574-3805

Importance Although several cancer drugs receive US Food and Drug Administration (FDA) approval each month, it is unclear how many of these cancer drugs transform the treatment landscape significantly by tumor group. Specifically, it remains unclear how many of these newly approved cancer drugs displace the existing standard-of-care therapies for their indication vs being added to existing therapies.Objective To examine how many cancer drugs displace the standard-of-care therapies vs being added to existing therapy or filling breaks in systemic treatments in the metastatic setting, adjuvant setting, or maintenance setting.Design, Setting, and Participants Retrospective cross-sectional study using landmark trials leading to FDA approval of cancer drugs between May 1, 2016, and May 31, 2021. The study evaluated all FDA approvals for cancer drugs between May 1, 2016, and May 31, 2021, using the FDA Oncology (Cancer)/Hematologic Malignancies Approval Notifications website. All clinical trials leading to FDA approval of cancer drugs during this period were examined.Main Outcomes and Measures A drug was determined to have displaced the prior standard-of-care therapy by evaluating the comparator arm (or lack thereof) in the clinical trial leading to the drug’s approval and also by reviewing National Comprehensive Cancer Network Guidelines. Cancer drug approvals were categorized as first-line displacing if a drug was approved for use in the first-line setting and displaced the prior standard-of-care drug for an indication, first-line drug alternatives/new if a drug was approved for use in the first-line setting but did not displace the standard of care at the time of approval or was a new drug that was first of its class for an approved indication, add on if a drug was approved in combination with a previously approved therapy for a disease or if a drug was approved for use in the adjuvant or maintenance settings, and later line if a drug was approved for use in t

Journal article

Lythgoe MP, Prasad V, 2022, The last word to new FDA draft guidance for cancer clinical trial eligibility criteria for patients with incurable cancer, Journal of Cancer Policy, Vol: 31, Pages: 100322-100322, ISSN: 2213-5383

Journal article

Benjamin DJ, Lythgoe M, Raymakers AJN, Rezazadeh Aet al., 2022, Cost effectiveness of newly approved second/third-line agents in metastatic urothelial carcinoma (mUC)., Journal of Clinical Oncology, Vol: 40, Pages: 574-574, ISSN: 0732-183X

<jats:p> 574 </jats:p><jats:p> Background: Over the past years, the treatment landscape of platinum-refractory mUC has drastically changed with the advent of immunotherapy. More recently, several new agents including enfortumab, erdafitinib, and sacituzumab have received F.D.A. approval for the treatment of platinum-refractory mUC. It is unclear if these newly approved therapies may be cost prohibitive for patients and/or hospitals/clinics compared to the recommended NCCN category 1 second-line agent, pembrolizumab. Methods: Using acquisition costs from our home institution’s cancer center pharmacy department, we calculated the total cost of treatment for each agent. We used phase II clinical trial data to determine the median duration of treatment for each therapy. For weight-based therapies, we used 70 kg as the weight for an average human adult. Results: The three newly approved therapies for mUC have total acquisition costs in descending order as follows: enfortumab vedotin ($153,697.50), edafitinib ($131,642.62), and sacituzumab govitecan ($63,198.07). Enfortumab and sacituzumab likely have higher total costs given both therapies require infusion center use for administration, and are associated with infusion center administration fees. In comparison, pembrolizumab (standard of care per NCCN guidelines) has a total acquisition cost of $51,343.60. Conclusions: Based off median duration of treatment, pembrolizumab has the lowest total acquisition cost compared to the three newly approved therapies for mUC. Further statistical analysis of this data set is ongoing. In particular, analysis will include out-of-pocket costs for patients as well as quality-adjusted life years (QALY).[Table: see text] </jats:p>

Journal article

Glover M, Hui G, Chiang R, Savage P, Krell J, Julve M, Grivas P, Lythgoe M, Khaki ARet al., 2022, Disparity of race reporting in US Food and Drug Administration drug approvals for urinary system cancers from 2006 to 2021, BJU International, Vol: 129, Pages: 168-170, ISSN: 1464-4096

Journal article

Lythgoe MP, Jenei K, Prasad V, 2022, Regulatory decisions diverge over aducanumab for Alzheimer’s disease, BMJ, Vol: 376, Pages: 1-2, ISSN: 1759-2151

Journal article

Lythgoe MP, Olivier T, Prasad V, 2021, The iceberg plot, improving the visualisation of therapy response in oncology in the era of sequence-directed therapy, EUROPEAN JOURNAL OF CANCER, Vol: 159, Pages: 56-59, ISSN: 0959-8049

Journal article

Powell K, Lythgoe MP, Prasad V, 2021, The Oncologic Drugs Advisory Committee Votes of April 2021-Implications for the Fate of Accelerated Approval., JAMA Oncol, Vol: 7, Pages: 1607-1609

Journal article

Haslam A, Lythgoe MP, Greenstreet Akman E, Prasad Vet al., 2021, Characteristics of Cost-effectiveness Studies for Oncology Drugs Approved in the United States From 2015-2020., JAMA Netw Open, Vol: 4

Importance: Increasingly, cost-effectiveness analyses are being done to determine the value of rapidly increasing oncology drugs; however, this assumes that these analyses are unbiased. Objective: To analyze the characteristics of cost-effectiveness studies and to determine characteristics associated with whether an oncology drug is found to be cost-effective. Design, Setting, and Participants: This retrospective cross-sectional study included 254 cost-effectiveness analyses for 116 oncology drugs that were approved by the US Food and Drug Administration from 2015 to 2020. Exposures: Each drug was analyzed for the incremental cost-effectiveness ratio per quality-adjusted life year, the funding of the study, the authors' conflict of interest, the threshold of willingness-to-pay, from what country's perspective the analysis was done, and whether a National Institute for Health and Care Excellence cost-effectiveness analysis had been done. Main Outcomes and Measures: The main outcome was the odds of a study concluding that a drug was cost-effective. Results: There were 116 drug approvals with 254 studies and country perspectives. Of the country perspectives, 132 (52%) were from the US. Forty-seven of 78 drugs with cost-effective studies had been shown to improve overall survival, whereas 15 of 38 of drugs without a cost-effectiveness study had been shown to improve overall survival. Having a study funded by a pharmaceutical company was associated with higher odds of a study concluding that a drug was cost-effective than studies without funding (odds ratio, 41.36; 95% CI, 11.86-262.23). Conclusions and Relevance: In this cross-sectional study, pharmaceutical funding was associated with greater odds that an oncology drug would be found to be cost-effective. These findings suggest that simply disclosing potential conflict of interest is inadequate. We encourage cost-effectiveness analyses by independent groups.

Journal article

Lythgoe MP, Prasad V, 2021, How the US Food and Drug Administration’s approval of aducanumab for Alzheimer's disease has implication for oncology and beyond, European Journal of Cancer, Vol: 157, Pages: 68-70, ISSN: 0959-8049

Journal article

Makrakis D, Talukder R, Diamantopoulos LN, Carril-Ajuria L, Castellano D, De Kouchkovsky I, Koshkin VS, Park JJ, Alva A, Bilen MA, Stewart TF, McKay RR, Santos VS, Agarwal N, Jain J, Zakharia Y, Morales-Barrera R, Devitt ME, Grant M, Lythgoe MP, Pinato DJ, Nelson A, Hoimes CJ, Shreck E, Gartrell BA, Sankin A, Tripathi A, Zakopoulou R, Bamias A, Murgic J, Frobe A, Rodriguez-Vida A, Drakaki A, Liu S, Kumar V, Di Lorenzo G, Joshi M, Isaacsson-Velho P, Buznego LA, Duran I, Moses M, Barata P, Sonpavde G, Yu EY, Wright JL, Grivas P, Khaki ARet al., 2021, Association of prior local therapy and outcomes with programmed-death ligand-1 inhibitors in advanced urothelial cancer, BJU INTERNATIONAL, ISSN: 1464-4096

Journal article

Middleton P, Hsu C, Lythgoe M, 2021, Clinical outcomes in COVID-19 and cirrhosis: a systematic review and meta-analysis of observational studies, BMJ Open Gastroenterology, Vol: 8, Pages: 1-10, ISSN: 2054-4774

Background: Coronavirus Disease 2019 (COVID-19) continues to pose a significant healthcare challenge throughout the world. Co-morbidities including diabetes and hypertension are associated with a significantly higher mortality risk. However, the effect of cirrhosis on COVID-19 outcomes has yet to be systematically assessed.Objectives: To assess the reported clinical outcomes of patients with cirrhosis who develop COVID-19 infectionDesign/Method: Pubmed and Embase databases were searched for studies included up to 3rd February 2021. All English language primary research articles that reported clinical outcomes in patients with cirrhosis and COVID-19 were included. The study was conducted and reported in accordance with the PRISMA guidelines. Risk of bias was assessed using the QUIPS risk of bias assessment instrument for prognostic factor studies template. Meta-analysis was performed using Cochrane Revman 5.4 software using a random effects model.Results: 63 studies were identified reporting clinical outcomes in patients with cirrhosis and concomitant COVID-19. Meta-analysis of cohort studies which report a non-cirrhotic comparator yielded a pooled mortality odds ratio (OR) of 2.48 (95% CI 2.02 – 3.04). Analysis of a subgroup of studies reporting OR for mortality in hospitalised patients adjusted for significant confounders found a pooled adjusted OR 1.81 (CI 1.36-2.42).Conclusion: Cirrhosis is associated with an increased risk of all cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection such as shielding and prioritisation of vaccination.

Journal article

Lythgoe MP, Ghani R, Mullish BH, Marchesi JR, Krell Jet al., 2021, The Potential of Faecal Microbiota Transplantation in Oncology, Trends in Microbiology, ISSN: 0966-842X

Journal article

Chiang RS, Glover M, Hui G, Desai A, Wakelee HA, Lythgoe M, Khaki ARet al., 2021, Racial diversity and reporting in FDA registration trials for thoracic malignancies from 2006 to 2020., Journal of Clinical Oncology, Vol: 39, Pages: 1-1, ISSN: 0732-183X

Background: Black patients have a disproportionately high incidence and mortality from lung cancer. Despite the importance of clinical trials, there continue to be significant racial disparities in recruitment for pivotal registration studies. In 2016, the FDA recommended reporting racial enrollment with a minimum of 5 categories (White, Black, Asian, American Indian or Alaskan Native [AIAN] and Native Hawaiian or Pacific Islander [NHPI]). The International Committee of Medical Journal Editors also recommend reporting race and ethnicity. We evaluated race reporting and representation in registration trials for thoracic cancers. Methods: We reviewed the FDA website and identified all new drug licensing indications in thoracic malignancies (small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and mesothelioma) from 2006 to 2020. NSCLC was further classified as EGFR+, ALK+, other mutation and NOS (no driver mutation). Clinical trials cited on the licensing label for market authorization were recorded and the corresponding registration trial publication was identified. If race was unreported or underreported (defined as ≤3 groups) in the licensing study, then additional information was obtained from clinicaltrials.gov. We calculated the proportion of registration trials meeting FDA criteria and the proportion of each racial group in trials. Results: From 2006-2020, we identified 55 new licensing indications, involving 26 unique drugs; 5 approvals in SCLC, 49 approvals in NSCLC and 1 in mesothelioma. Prior to the FDA race reporting guidelines, 33% (6/18) of registration studies did not meet FDA requirements. This improved to 27% (10/37) after the guideline introduction. Overall 29,545 patients participated in thoracic registration trials; 66% White, 22% Asian, 2% Black, <1% AIAN, <1% NHPI, 1% other or multiple races and 9% unknown. Table shows race distribution by cancer subtype. Conclusions: Although improving, a substantial number of registrationa

Journal article

Lythgoe MP, Prasad V, 2021, The FDA's latest move to expand eligibility for oncology trials - a double-edged sword?, Nature Reviews Clinical Oncology, Vol: 18, Pages: 745-746, ISSN: 1759-4774

Journal article

Lythgoe MP, Liu DSK, Annels NE, Krell J, Frampton AEet al., 2021, Gene of the month: lymphocyte-activation gene 3 (LAG-3), JOURNAL OF CLINICAL PATHOLOGY, Vol: 74, Pages: 543-547, ISSN: 0021-9746

Journal article

Lythgoe M, Cleary S, Kalofonou F, Grunewald T, Miller R, Cartwright D, Glasspool RM, Jones R, Rossides S, Ratnakumaran R, Michael A, McNeish I, Tookman L, Krell Jet al., 2021, 747P Real-world experience of rucaparib in patients with ovarian cancer: A multicentre United Kingdom study, Annals of Oncology, Vol: 32, Pages: S742-S742, ISSN: 0923-7534

BackgroundEpithelial Ovarian Cancer (EOC) is the 5th leading cause of female cancer deaths. Despite high responses to first-line therapy, 5-year survival remains poor at 29%. Rucaparib is a small molecule PARP inhibitor (PARPi) approved as monotherapy for maintenance treatment of recurrent EOC with prior complete/partial response to platinum-based chemotherapy, on the basis of the ARIEL3 trial. Despite the validity of clinical trial evidence, applicability to routine practice is limited and real-world evidence (RWE) is mandated.MethodsWe performed a multi-center retrospective study of patients with advanced EOC receiving rucaparib in the UK from June 2018, via an early access program.Results119 patients were included, with a median age of 66 years (range 26-89). Median ECOG at commencement was 1 (0-3). 91% (n=108) had high grade serous carcinoma and 24% (n=29) germline/somatic BRCA1/2mutation (BRCAm). Prior to rucaparib, patients had a median of 3 therapies (range 1-9) with 8% (n=10) receiving an alternate PARPi. Overall progression free survival (PFS) was 7.5 months (1.1-37.4), with a higher PFS of 9.1 months (1.1-35.5) in BRCAm patients. This is lower than observed in ARIEL3. However, if similar inclusion/exclusion criteria are applied to our RWE population, findings are analogous, with PFS of 10.2 and 16.6 months in the overall and BRCAm groups respectively. Treatment-related toxicity (any grade) was reported in 88% (n=105) of patients, most prevalent being nausea, fatigue, anaemia and other blood dyscrasias. 26% (n=32) of patients experienced a CTCAE grade 3/4 toxicity and 58% (n=69) required dose interruption/reduction. 13% (n=16) of patients discontinued therapy due to a treatment related adverse effect: most frequently fatigue, nausea or thrombocytopenia. No haematological malignancies were observed.ConclusionsOverall we found a lower incidence of any grade and grade 3/4 toxicity, and furthermore equivalent discontinuation rates to ARIEL3. A lower overall PFS

Journal article

Lythgoe M, Adriani M, Stebbing J, Clark J, Pickford E, Frampton A, Liu D, Kyrgiou M, Rees E, Fyvie G, Stevenson A, Krell Jet al., 2021, 543P Neoadjuvant MRx0518 treatment is associated with significant gene and metagene signature changes in solid tumours, Annals of Oncology, Vol: 32, Pages: S607-S607, ISSN: 0923-7534

BackgroundMRx0518 is an oral live biotherapeutic with potent immunostimulatory activity and anti-tumorigenic efficacy in murine models of lung (LLC1), kidney (Renca) and breast (EMT6) cancer. Previous reports have demonstrated a favourable safety profile in neoadjuvant and metastatic clinical settings, with emerging evidence of immune modulation. We performed a comprehensive analysis of the gene and metagene signature in cancer patients treated with MRx0518 monotherapy.MethodsTreatment-naïve patients with a histologically confirmed diagnosis of cancer scheduled for surgical resection were recruited from April 2019 to February 2020. Patients received 1 capsule of MRx0518 (1x1010 to 1x1011CFU) twice daily from inclusion until the day preceding surgery. Safety and tolerability (CTCAE v4.03) were the primary endpoints of this study. Comprehensive biomarker analysis was also performed in paired pre-treatment (diagnostic biopsy) and post-treatment (surgical specimen) samples using the NanoString IO 360 panel to explore gene and metagene signatures.Results31 samples were collected across tumour groups including breast (n=13) prostate (n=8), uterine (n=6), melanoma (n=2) and bladder (n=2). Differential expression analysis showed significant (p<0.05) increases in genes and metagenes associated with anti-tumour activity, including antigen presentation (AXL & CXCL12), innate immune processes (CHUK, RELA, PPARG & HRAS), interferon response (IFNGR1 & IFNGR2), Th1 cells and CD8+ cells following MRx0518 therapy, echoing preclinical findings. Novel changes, not previously detected in murine models, involving endothelial, mast cells, inflammatory myeloid and inflammatory chemokines were also observed, suggesting MRx0518 may have additional in vivo anti-tumorigenic effects. These changes were more pronounced in the breast cancer cohort.ConclusionsThis analysis, mirrors previous immunostimulatory activity and anti-tumorigenic efficacy observations seen in pre-clini

Journal article

Abdelmalak R, Lythgoe MP, Evans J, Flynn M, Waters J, Webb A, Pinato DJ, Sharma Ret al., 2021, Exploration of novel prognostic markers in grade 3 neuroendocrine neoplasia, Cancers, Vol: 13, Pages: 1-12, ISSN: 2072-6694

Background: High-grade neuroendocrine tumours and carcinomas (NET/NECs) behave aggressively, typically presenting at an advanced stage. Prognosis is poor, with median survival between 5 and 34 months. The mainstay of treatment is palliative systemic therapy. However, therapy carries a risk of toxicity, which can reduce quality of life. Therefore, accurate prognostic scores for risk stratification of patients with high-grade NET/NECs are needed to help guide patient management to decide whether active treatment is likely to improve overall survival (OS). We aimed to compare the prognostic ability of published prognostic scores to predict OS in a cohort of patients with high-grade NET/NECs of any primary site. Methods: Treatment, biochemical and clinicopathological data were collected retrospectively from 77 patients with high-grade NET/NECs across three hospitals between 2016 and 2020. Variables including performance status (PS), Ki-67, age at diagnosis, previous treatment and presence of liver metastases were recorded. Pre-treatment neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, modified Glasgow prognostic score (mGPS), and gastrointestinal neuroendocrine carcinoma (GI-NEC) score were derived. Univariable and multivariable survival analyses were used to assess prognostic ability. Results: The median age of the cohort was 63 years (range: 31–85); 53% of subjects were female. Grade 3 NETs (G3-NETs) were identified in 32 patients and NECs in 45 patients. The median OS was 13.45 months (range: 0.87–65.37) with no difference observed between G3-NETs and NECs. Univariable analysis revealed that NLR (n = 72, p = 0.049), mGPS (n = 56, p = 0.003), GI-NEC score (n = 27, p = 0.0007) and Ki-67 (n = 66, p = 0.007) were significantly associated with OS. Multivariable analysis confirmed that elevated mGPS (p = 0.046), GI-NEC score (p = 0.036), and Ki-67 (p = 0.02) were independently prognostic for reduced OS across the entire cohort. mGPS was identified

Journal article

Sharma R, Lythgoe MP, Slaich B, Patel Net al., 2021, Exploring the epigenome in gastroenteropancreatic neuroendocrine neoplasias, Cancers, Vol: 13, Pages: 1-18, ISSN: 2072-6694

Gastroenteropancreatic neuroendocrine neoplasias are a diverse group of neoplasms with different characteristics in terms of site, biological behaviour and metastatic potential. In comparison to other cancers, they are genetically quiet, harbouring relatively few somatic mutations. It is increasingly becoming evident that epigenetic changes are as relevant, if not more so, as somatic mutations in promoting oncogenesis. Despite significant tumour heterogeneity, it is obvious that DNA methylation, histone and chromatin modifications and microRNA expression profiles are distinctive for GEP-NEN subtypes and may correlate with clinical outcome. This review summarises existing knowledge on epigenetic changes, identifying potential contributions to pathogenesis and oncogenesis. In particular, we focus on epigenetic changes pertaining to well-differentiated neuroendocrine tumours, which make up the bulk of NENs. We also highlight both similarities and differences within the subtypes of GEP-NETs and how these relate and compare to other types of cancers. We relate epigenetic understanding to existing treatments and explore how this knowledge may be exploited in the development of novel treatment approaches, such as in theranostics and combining conventional treatment modalities. We consider potential barriers to epigenetic research in GEP-NENs and discuss strategies to optimise research and development of new therapies.

Journal article

Lythgoe MP, Krell J, McNeish IA, Tookman Let al., 2021, Safe administration of chemotherapy in mast cell activation syndrome, Journal of Oncology Pharmacy Practice, Vol: 27, Pages: 1005-1010, ISSN: 1078-1552

IntroductionMast Cell Activation Syndrome (MCAS) is an immunogenic disorder typically presenting with episodic multi-organ symptoms, caused by the inappropriate and aberrant release of mast cell mediators. Symptoms may be severe, including anaphylaxis and often occur in response to specific triggers which include many drugs and potentially chemotherapeutic agents. The administration of adjuvant chemotherapy and radiotherapy in endometrial cancer significantly reduces the risk of reoccurrence in patients with high risk disease. Currently there is no evidence or case reports to guide the safe administration of chemotherapy in MCAS patients.Case reportWe present the case of a 59-year-old lady with stage 3 A grade 2 endometroid endometrial cancer who underwent successful surgical management. She then received 4 cycles of adjuvant chemotherapy in the form of carboplatin and paclitaxel. This case describes a staged approach to chemotherapy administration and the utilisation of a carboplatin desensitization regimen to reduce the risk of immediate and delayed hypersensitivity sequalae.Management & outcome: Utilising an enhanced pre-medication strategy and a staged approach to chemotherapy administration, she was able to complete adjuvant treatment without any serious complications. At the date of censoring (May 2020) she has not shown any evidence of disease re-occurrence.Discussion & conclusion: Administering chemotherapy to patients with any mast cell disorder remains challenging. We hope that this case may provide the framework for safer chemotherapy administration for any patients at high risk of serious hypersensitivity sequalae in endometrial cancer and beyond.

Journal article

Lythgoe M, Krell J, Warner JL, Desai A, Khaki ARet al., 2021, Time intervals between U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) new cancer therapy approvals., Journal of Clinical Oncology, Vol: 39, Pages: 1575-1575, ISSN: 0732-183X

Background: Novel therapies are transforming cancer care. Regulatory review and approval are essential to deliver safe and efficacious innovations to patients. Studies prior to 2010 describe quicker approval decisions for new oncology drug registrations with the FDA compared to the EMA (median delay 238 days). Both regulatory agencies have subsequently improved procedures to expedite approval times. We compared regulatory market authorisation dates at the FDA and EMA for new oncology therapies from 2010-2020. Methods: New oncology therapeutic approvals between 2010-2020 were identified from the FDA and EMA regulatory databases. We analysed only initial approvals (not supplementary licenses) for active anti-cancer therapies (excluding biosimilars and supportive drugs). The delay in regulatory approval between the FDA and EMA was calculated in calendar days. We further analysed therapies by therapeutic class, evaluating for significant differences. Results: We identified 108 new therapy registrations during the study period. 104 (96.3%) therapies were approved by the FDA and 90 (83.3%) had EMA market authorisation. 4 (3.7%) drugs were not FDA registered, including 3 unsuccessful applications and 1 which sought licensing in a different indication. 18 (16.5%) drugs were not EMA registered, including 9 (8.8%) which did not pursue EMA licensing, 3 (2.9%) withdrawn licensing applications, 3 (2.9%) sought licensing in different tumour group/indication, 1 (0.9%) rejected application and 2 (1.9%) with applications under review at submission date. Of the 86 drugs approved by both agencies, 80 were approved first by the FDA and 6 by the EMA. The median delay in approval between the FDA and EMA was 227 days (IQR:124-354 days). Table shows approvals by therapeutic class. The shortest median time difference for approval was for monoclonal antibodies (171 days) with the longest for kinase inhibitors (281 days). Conclusions: This study shows more new oncology therapies are approved

Journal article

Lythgoe MP, Krell J, Kenny L, Khaki ARet al., 2021, 157P Racial diversity and reporting in FDA registration trials for breast cancer from 2006 to 2021, Annals of Oncology, Vol: 32, Pages: S88-S88, ISSN: 0923-7534

BackgroundIn the USA, there are >250,000 diagnoses of breast cancer (BC) annually, with significant racial disparities in incidence, subtype and outcomes. FDA clinical trials guidance recommend 5 categories of race reporting (White, Black, Asian, American Indian/Alaskan Native [AIAN] & Native Hawaiian/Pacific Islander [NHPI]). Furthermore, International Committee of Medical Journal Editors (ICMJE) guidance recommend authors, as a minimum, provide descriptive data for race. We analysed racial diversity in BC drug registration trials and compliance with FDA/ICMJE guidance.MethodsWe performed a retrospective review of BC FDA market authorisations from 2006 to 2021. Clinical trial publications cited on the licensing label were identified and analysed. If race was under-reported (<3 groups), the study report on clinicaltrials.gov was analysed. The total proportion of racial group participation and number of registration trials with adequate reporting was determined.Results38 new licensing indications were identified, involving 41 trials and 23 drugs. Overall, 36,081 patients participated: 19,495 (54.0%) White, 4194 (11.6%) Asian, 748 (2.1%) Black, 228 (0.6%) AIAN, 8 (0.1%) NHPI, 840 (2.3%) other and 10568 (29.3%) unknown. The table shows breakdown by BC subtype. Race was reported in 29 (70%) licensing trial publications, of which 7 provided only limited data. For licensing trials where no race data was reported, a further 6 (14%) had information within the study report. In the 10 years prior to the introduction of new FDA guidance in 2016 only 50% of registration studies met FDA/ICJME race reporting requirements. Since 2016 this has improved to 85%

Journal article

Lythgoe MP, Krell J, Savage P, Prasad Vet al., 2021, Race reporting and diversity in US food and drug administration (FDA) registration trials for prostate cancer; 2006-2020., Prostate Cancer and Prostatic Diseases, Vol: 24, Pages: 1208-1211, ISSN: 1365-7852

BACKGROUND: There is significant racial disparity in prostate cancer (PCa) in terms of incidence, treatment, and outcomes. Racial diversity and compliance with FDA race reporting guidelines in PCa drug registration trials are unknown. We analyzed racial diversity and race reporting in drug licensing trials for PCa. METHODS: New drug authorizations for PCa from 2006 to 2020 were identified. The corresponding licensing trial publications were analyzed to check compliance with current FDA recommendations for race reporting. If race was unreported, the clinical trial report was analyzed to determine participant recruitment by race and lead the recruiting country. RESULTS: During the study period, 17 new drug registrations for the management of PCa involving ten unique drugs were identified. In total, 18,455 participants were included in FDA registration trials, of which 76.3% were white or Caucasian, 7.9% Asian, 2.9% Black or African American, 0.5% American Indian or Alaskan Native, 0.1% Native Hawaiian or other Pacific Islander, 1.8% other or multiple races and 10.5% unknown. 53% of trials reported race in the licensing publication, however of this only 55% met current FDA recommendations. When the race was unreported in the licensing publication, 88% of studies had further information in the clinical study report. CONCLUSION: We found a significant under-representation of non-white participants in FDA drug registration trials for PCa. Race reporting in licensing publication is inconsistent and both FDA and International Committee of Medical Journal Editors guidelines are not being universally followed. Given the disproportionality of the disease burden of PCa, recruitment of Black and other minority participants to trials should be a research priority.

Journal article

Lythgoe MP, Cheng VWT, McKenzie HS, Kwan A, Konstantis A, Ma R, Teo PJ, Fitzpatrick A, Lythgoe MPet al., 2021, V6 PRIMROSE: A national trainee collaborative-led, multicentre prospective audit on the care of breast cancer patients with central nervous system disease in the UK, BJS Open, Vol: 5, Pages: 1-1, ISSN: 2474-9842

PRIMROSEA national trainee collaborative-led, multicentre prospective audit on the care of breast cancer patients with central nervous system disease in the UKMark P Lythgoe1, Vinton WT Cheng2, Hayley S McKenzie3, Amy Kwan4, Apostolos Konstantis5, Ruichong Ma6, Pei J Teo7, Amanda Fitzpatrick8, Laura Woodhouse9 & Carlo Palmieri10 on behalf of the BNTRC† and PRIMROSE study group1Imperial College Healthcare NHS Trust, London, 2Leeds Cancer Centre, Leeds, 3University of Southampton, Southampton, 4University of Sheffield, Sheffield, 5The Princess Alexandra NHS Trust, Harlow 6Oxford University Hospitals NHS Trust, Oxford, 7Worcestershire Acute Hospitals NHS Trust, Worcester, 8Institute of Cancer Research, London, 9The Christie NHS Foundation Trust, Manchester, 10University of Liverpool, Liverpool, †British Neurosurgical Trainee Research CollaborativeIntroductionBreast cancer is the commonest cancer in the UK and the 4th leading cause of cancer-related death. Breast cancer brain metastases (BCBM) are a poor prognostic indicator and associated with very poor survival and only a minority of patients survive >1 year despite oncological treatment. The rising prevalence of patients with BCBM represent an increasing unmet healthcare need. However, in the UK there is a paucity of data about prevalence, survival and management. Guidance on managing brain metastases is improving, however it is unclear how this has been applied in the context of BCBM and whether recommended standards are uniformly applied across the UKMethodsPRIMROSE is a trainee collaborative-led initiative to estimate BCBM prevalence, assess current practice (comparing national/international standards) and determine long term outcomes/sequalae. Anonymised data is being pooled via secure REDCap database collating demographics, clinico-pathological information, prior treatment, BCBM treatment and other key variables. All UK hospitals can register, with recruitment driven by trainees via the UK B

Journal article

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