Oncology Drug Research Articles

Subgroup identification of targeted therapy effects on biomarker for time to event data.

The initiation biomarker-driven trials have revolutionized oncology drug development by challenging the traditional phased approach and introducing basket studies. Notable successes in non-small cell lung cancer (NSCLC) with ALK, ALK/ROS1, and EGFR inhibitors have prompted the need to expand this approach to other cancer sites. This study explores the use of dose response modeling and time-to-event algorithms on the biomarker molecular targeted agent (MTA). By simulating subgroup identification in MTA-related time-to-event data, the study aims to develop statistical methodology supporting biomarker-driven trials in oncology. A total of n patients are selected assigned for different doses. A dataset is prepared to mimic the situation on Subgroup Identification of MTA for time to event data analysis. The response is measured through MTA. The MTA value is also measured through ROC. The Markov Chain Monte Carlo (MCMC) techniques are prepared to perform the proposed algorithm. The analysis is carried out with a simulation study. The subset selection is performed through the Threshold Limit Value (TLV) by the Bayesian approach. The MTA is observed with range 12-16. It is expected that there is a marginal level shift of the MTA from pre to post-treatment. The Cox time-varying model can be adopted further as causal-effect relation to establishing the MTA on prolonging the survival duration. The proposed work in the statistical methodology to support the biomarker-driven trial for oncology research. This study extends the application of biomarker-driven trials beyond NSCLC, opening possibilities for implementation in other cancer sites. By demonstrating the feasibility and efficacy of utilizing MTA as a biomarker, the research lays the foundation for refining and validating biomarker use in clinical trials. These advancements aim to enhance the precision and effectiveness of cancer treatments, ultimately benefiting patients.

An Analysis of Dosing-Related Postmarketing Requirements for Novel Oncology Drugs Approved by the U.S. Food and Drug Administration, 2012-2022.

The FDA's Oncology Center of Excellence's (OCE) launch of Project Optimus signals increased focus on dose optimization approaches in oncology drug development, particularly toward optimization in the premarket setting. Although sponsors continue to adapt premarket study designs and approaches to align with FDA's expectations for dose optimization, including consideration of the optimal dosage(s), there are still instances where questions remain at the time of approval about whether the approved doses or schedules are optimal. In these cases, FDA can exercise regulatory flexibility by issuing postmarketing requirements (PMR) and avoid delaying patient access to promising therapies. This landscape analysis demonstrates that over the past decade (2012-2022), FDA frequently used PMRs to answer additional questions about dosing for novel oncology approvals. We found more than half of drugs (78/132, 59.1%) had a dosing PMR and observed a recent increase in PMRs intended to evaluate whether a lower dose could be more optimal. These results suggest there are opportunities to adapt premarket dose optimization strategies and leverage innovative development tools to ensure timely identification of the optimal dose.

ASCO Ethical Guidance for the Practical Management of Oncology Drug Shortages.

ASCO Ethical Guidance for the Practical Management of Oncology Drug Shortages.

Characteristics and outcomes of new molecular oncology drug approvals, in combination or monotherapy

ImportanceUnderstanding the factors that are associated with new molecular entity (NME) cancer drug approvals as a single agent and in combination, and European Society for Medical Oncology (ESMO) scores, can aid in identifying suitable factors to consider in trial designs for future drugs. In addition, the association between the various outcomes can aid in determining benefit when surrogate outcomes are used in approval consideration. ObjectiveThis study aims to (1) use the measures used in evaluating clinical trials by ESMO scores to determine the differences in the characteristics of 2013–2022 Food and Drug Administration (FDA) oncology NME drug approvals for those approved for use in combination or as a monotherapy, and (2) analyze the association between survival outcomes and the response rate for monotherapy NME drugs and/or drugs approved in combination. DesignCross-sectional analysis. SettingUS FDA Oncology Drug Approvals (2013–2022) ParticipantsUS FDA Oncology Drug Approvals (2013–2022) ExposuresTrial-level characteristics (tumor types, basis of approval, randomized or not, phase) and associations between overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) and whether NME drugs were approved as monotherapy or in combination . ResultsDrugs approved for use as a monotherapy are less likely to be approved using a randomized study (p < 0.001) and more likely to be approved via the accelerated pathway (p = 0.012) and be open-label (p < 0.001). Drugs approved for use as a combination or monotherapy significantly differed on their approval basis (p = 0.002), phase of trial at the time of approval (p = 0.02), and ESMO scores (p = 0.02). There was low correlation between response rate and either PFS or OS metrics. However, nearly all of the drugs with large improvements in OS (> 5months) were drugs with robust ORR. Conclusions and relevanceDrugs approved as monotherapy with a low response rate are likely to have marginal benefit in OS and PFS.

Utility of Physiologically Based Pharmacokinetic Modeling to Investigate the Impact of Physiological Changes of Pregnancy and Cancer on Oncology Drug Pharmacokinetics.

The treatment of cancer during pregnancy remains challenging with knowledge gaps in drug dosage, safety, and efficacy due to the under-representation of this population in clinical trials. Our aim was to investigate physiological changes reported in both pregnancy and cancer populations into a PBPK modeling framework that allows for a more accurate estimation of PK changes in pregnant patients with cancer. Paclitaxel and docetaxel were selected to validate a population model using clinical data from pregnant patients with cancer. The validated population model was subsequently used to predict the PK of acalabrutinib in pregnant patients with cancer. The Simcyp pregnancy population model reasonably predicted the PK of docetaxel in pregnant patients with cancer, while a modified model that included a 2.5-fold increase in CYP2C8 abundance, consistent with the increased expression during pregnancy, was needed to reasonably predict the PK of paclitaxel in pregnant patients with cancer. Changes in protein binding levels of patients with cancer had a minimal impact on the predicted clearance of paclitaxel and docetaxel. PBPK modeling predicted approximately 60% lower AUC and Cmax for acalabrutinib in pregnant versus non-pregnant patients with cancer. Our results suggest that PBPK modeling is a promising approach to investigate the effects of pregnancy and cancer on the PK of oncology drugs and potentially inform dosing for pregnant patients with cancer. Further evaluation and refinement of the population model are needed for pregnant patients with cancer with additional compounds and clinical PK data.

MSR44 Inflation, the Usual Suspect: Are Oncology Drugs Really Victims of the Macroeconomic Context?

MSR44 Inflation, the Usual Suspect: Are Oncology Drugs Really Victims of the Macroeconomic Context?

EPH78 A Review of Patient-Reported Outcomes and External Control Arms in Regulatory Submissions of Novel Oncology Drugs

EPH78 A Review of Patient-Reported Outcomes and External Control Arms in Regulatory Submissions of Novel Oncology Drugs

Abstract A007: Preclinical bone metastasis technology platform – Predictive evaluation of experimental therapies on bone metastasis

Abstract Most cancer deaths are due to metastases, and bone metastases are a considerable problem especially in breast and prostate cancer, being developed in 70-90% of advanced-stage patients. Despite major investments in oncology drug development, bone metastases are currently incurable and a high unmet medical need with only 5% of patients being alive 5 years after the diagnosis. Development of therapies for bone metastasis has been challenging due to lack of appropriate preclinical models available to support decision making in next phases of drug development. In the absence of clinically relevant preclinical bone metastasis models, the current strategy is to rely on preclinical efficacy data obtained with subcutaneous models that lack the clinically relevant local tissue microenvironment, which has a major impact on tumor growth. The use of clinically non-relevant models in preclinical-stage development may be one important reason for the current &amp;gt;95% failure rate of oncology drugs in clinical trials. To support predictive evaluation of therapies for bone metastatic cancers, we describe a preclinical bone metastasis technology platform for evaluating efficacy of novel therapies on bone metastases. The platform utilizes tumors growing in bone microenvironment, mimicking growth of bone metastases in patients. Syngeneic or humanized mouse models with tumor and immune cells of same species are needed for supporting development of immunotherapies, allowing interactions of tumor and immune cells in the bone metastatic microenvironment, according to the novel osteoimmuno-oncology concept. The platform provides a predictive tool for studying unique biological features associated with different types of bone metastases in cancer-type specific manner. Here we summarize case examples where results from preclinical bone metastasis studies align with clinical findings of different therapies approved or evaluated for bone metastasis. Zoledronic acid, an anti-resorptive bisphosphonate that is currently used in breast cancer patients with bone metastases to prevent cancer-induced bone loss, showed improved bone health but no effects on tumor growth. Radium-223 dichloride, an approved treatment for bone metastatic castration-resistant prostate cancer in patients, showed reduced prostate cancer growth and decreased tumor-induced bone changes. As for immunotherapies, an IDO1 inhibitor had no effects on breast cancer bone metastases and the anti-PD-1 antibody pembrolizumab had no effects on breast and prostate cancer bone metastases, predicting recent clinical findings that demonstrate lack of efficacy of anti-PD-1 in clinical prostate cancer trials. We conclude that the bone metastasis technology platform is a biologically relevant tool for preclinical evaluation of the efficacy of experimental therapies on bone metastasis, and it has been validated with positive and negative case examples, demonstrating its clinically predictive power. Citation Format: Tiina E Kähkönen, Jussi M Halleen, Jenni Bernoulli. Preclinical bone metastasis technology platform – Predictive evaluation of experimental therapies on bone metastasis [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A007.

Abstract PR016: Largescale organoid panel drug screening to short-track clinically-relevant output

Abstract Introduction Patient-derived organoids (PDOs) have emerged over the last decade as representative in vitro replicas of tumor biology, bringing increased accuracy in predicting clinical outcomes based on pre-clinical results. Large and deeply characterized organoid biobanks, covering broad varieties in indications and genetic backgrounds, have been generated that allow large scale (combination) drug testing, reliable biomarker predictions, and improved drug repurposing and patient stratification studies. However, relatively long timelines and high expenses hold the organoids back to live up to their promise. To overcome these hurdles, we have optimized processes, and here present a largescale organoid panel drug screening platform consisting of over 50 organoid models that predicts drug responses across at least seven indications in a robust, but also fast and cost-efficient manner. Methods Colorectal, breast, lung, pancreatic, ovarian, cervix and melanoma organoid models were selected for subtype and driver mutation variety, banked in large batches, and preserved in an assay-ready format to reduce lead-in time and organoid expansion phase. Drug responses of the full organoid panel were characterized with standard of care compounds (cisplatin, gemcitabine and paclitaxel) and AMG510 targeted therapy (KRAS G12C inhibitor, sotorasib) by measuring ATP levels after a 5-day exposure using a 9-dose curve. Experiments were executed using automated liquid handling equipment to standardize procedures and increase consistency. Control variability (CV), Z-factors and assay windows were calculated to assess assay performance, and IC50 values and area under the curves (AUC) were calculated to express drug sensitivity. Experiments were repeated in multiple labs to test for assay robustness. Results The largescale panel screening platform exhibits a high average assay performance, with high Z-factors (&amp;gt;0.6), low intra- and interplate variability (CV &amp;lt;15%) and reproducible IC50 outputs. Data report of the full panel was prepared within 6 weeks of project kick-off; shortening timelines compared to regular organoid screens over 6-fold, from months to weeks. Using IC50 values and AUC, drug sensitivity testing distinguished sensitive from partially and insensitive models, and models with specific genetic features (KRAS G12C vs G12X) behaved as expected when a AMG510 therapy was tested. Conclusion and Discussion Assay-ready organoid technology-based largescale panel screening as presented here has resulted in efficient timeline and cost reductions and will therefore further harness the large potential of PDO technology in the drug development pipeline. Largescale organoid panel screening enables identification of drug synergy by testing drug combinations. With the majority of included models also being available as PDX models, it will facilitate a seamless translation into subsequent in vivo studies. Moreover, combining panel screens with advanced biomarker analysis will allow early patient stratification, further aiding clinical development of novel oncology drugs. Citation Format: Liza Wijler, Annelot Staes, Linda van Seeters, Lama Alhaj Hasan, Bram Herpers, Leo Price, Mariusz Madej, Michiel Fokkelman, Xiaoxi Xu, Marrit Putker. Largescale organoid panel drug screening to short-track clinically-relevant output [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr PR016.

Analysis of Medicare Expenditure for Discarded Infused Cancer Therapeutics From 2017-2020.

To explore patterns in Medicare reimbursement for wasted oncologic and hematologic infusion drugs from 2017 to 2020 and estimate the savings that implementation of the Infrastructure Investment and Jobs Act (IIJA) would have had. Using the publicly available Medicare Part B Discarded Drug Units database, we analyzed reimbursement data for discarded antineoplastic and hematology therapies from 2017 to2020. Medicare Part B utilization data was extracted for 77 therapies. From 2017 to 2020, the median annual dollar value of discarded therapies was $590 million. Every year, bortezomib, azacitidine, cabazitaxel, and decitabine were among the most wasted products, an average 24% waste. The IIJA policy would have impacted a median of 20 oncology agents and resulted in median annual refund of $172 million. Had the top five most discarded therapies been redistributed, they could have treated 18,289 patients. The five most wasted drugs were all dosed by weight and distributed in single-use vials. The IIJA could potentially significantly reduce waste or encourage redistribution to treat thousands of additional patients. We propose that a fusion of fixed and weight-based dosing may help reduce wasteful medication administration by offering doses that better accommodate most patients. We anticipate that manufacturers will adapt to the IIJA perhaps by adjusting fixed doses or simply increasing drug prices. If price changes from dose delivery adjustment occur, rebates offered to pharmacy benefit managers and insurers will likely follow suit and may alter formulary positioning.

RWD90 How to Reduce the Burden of Travel for the Patients? a Proof of Concept (POC) for Oncological Oral Drugs Distribution Points Analysis

RWD90 How to Reduce the Burden of Travel for the Patients? a Proof of Concept (POC) for Oncological Oral Drugs Distribution Points Analysis

HTA90 Quality of Clinical Evidence Submitted to a National HTA Agency in Ireland: 10 Years of Drugs for Oncology

HTA90 Quality of Clinical Evidence Submitted to a National HTA Agency in Ireland: 10 Years of Drugs for Oncology

PP079 Country contribution of investigators to pivotal clinical trials and their primary publications of new oncology drugs approved by the US Food and Drug Administration

PP079 Country contribution of investigators to pivotal clinical trials and their primary publications of new oncology drugs approved by the US Food and Drug Administration

HTA85 Will the New Dutch Criteria for Therapeutic Value for Oncology Drugs Create Inequalities in Access between Countries? a Review of Health Technology Assessment Oncology Submissions.

HTA85 Will the New Dutch Criteria for Therapeutic Value for Oncology Drugs Create Inequalities in Access between Countries? a Review of Health Technology Assessment Oncology Submissions.

HTA11 Drivers of Positive Health Technology Assessment Outcomes for Oncology Drugs in Three Global Markets

HTA11 Drivers of Positive Health Technology Assessment Outcomes for Oncology Drugs in Three Global Markets

Abstract A098: HBI-2376, HUYABIO clinical stage SHP2 inhibitor, displays efficacy signal in patients with KRAS mutations in early clinical studies

Abstract SHP2 is an attractive target in oncology drug development due to its dual roles in tumor progression: i) direct growth and proliferation of cancer cells; ii) acting as an immune checkpoint molecule to suppress tumor immunity. HBI-2376 is an orally bioavailable selective SHP2 inhibitor developed for the treatment of solid tumors harboring KRAS or EGFR mutations, such as non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic cancer (PAC). Additionally, HBI-2376 has the potential to suppress tumor growth via induction of the activity of immune infiltrating cells in the TME (tumor microenvironment). Preclinical studies showed greater potency of HBI-2376 to inhibit cell proliferation in a variety of cancer cell lines compared to other SHP2 inhibitors such as TNO-155 (Novartis AG) and RMC-4550 (Revolution Medicines). Additionally, HBI-2376 was found to be more efficacious in tumor growth inhibition than TNO-155 and RMC-4550 in NCI-H1975L858R_T790M_C797S osimertinib-resistant cell line and other tumor models. Furthermore, Western blotting showed inhibition of p-ERK and DUSP6 in HBI-2376 treated cells indicative of a biomarker of response to the therapy. In addition to xenograft models, we tested efficacy of HBI-2376 as single agent or in combination with anti-PD-1 mAb in MC38 CRC syngeneic model. HBI-2376 showed greater efficacy in tumor growth inhibition vs. TNO-155 and RMC-4550 both as single agent and in combination therapy. IHC data showed reduction in infiltration of M2 macrophages (F4/80+Arg1+) in the HBI-2376 treated tumors suggesting a mechanism of action for its greater efficacy in MC38 model. HBI-2376 is currently being tested in Phase 1 clinical trials. Consistent with preclinical studies, we have observed efficacy signals in early cohorts in two patients with partial responses (PR). Both patients were harboring KRAS mutations beyond KRAS G12C. Additionally, HBI-2376 was well tolerated with no SAEs or DLTs in the first four cohorts indicative of a good tolerability in cancer patients. Analysis of pERK in PBMCs isolated from the treated patients showed dose dependent inhibition in pERK further supporting a mechanism driven response to HBI-2376. Therefore, the preclinical and clinical data may represent HBI-2376 as the best-in-class SHP2 inhibitor. Citation Format: Farbod Shojaei, Jill M Ricono, Che Fang, Yan Xing, John Ning, Gloria Lee, Mireille Gillings. HBI-2376, HUYABIO clinical stage SHP2 inhibitor, displays efficacy signal in patients with KRAS mutations in early clinical studies [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A098.

Abstract A045: EZH2 inhibition re-sensitizes drug resistant triple-negative breast cancer PDX models to Eribulin

Abstract Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer predominantly affecting younger women. The mainstay of treatment is chemotherapy, to which most patients eventually stop responding. After demonstrating improved overall survival in the metastatic setting, eribulin, a microtubule inhibitor, was approved for the treatment of late-stage, heavily pretreated breast cancer. While frequently used in the clinic, most patients either do not respond initially or they stop responding to eribulin. Considering that there is a lack of oncology drugs including targeted therapies to treat TNBCs, patients are therefore left with few therapeutic options after eribulin. There is a paucity of data on mechanisms of acquired resistance to eribulin, and few potential uncovered targetable alterations. The goal of our study is to determine mechanisms of acquired resistance to Eribulin using isogenic acquired-resistant PDX models and to attempt to reverse this resistance with novel combinations. Methods: PDX models are grown as mammary fat pad engraftments of patient tumours in immuno-compromised (NGS) mice. To determine drug response, we treat tumour-bearing mice with weekly eribulin, measure the tumor volume once per week, then classify response based on mRECIST 1.1 criteria. Acquired resistance was generated in vivo in TNBC PDXs via the continuous or interrupted treatment of Eribulin in sensitive models that regressed on Eribulin. RNA-Seq analysis was performed on isogenic pairs of Eribulin sensitive and resistant PDX tumors and analyzed for differential gene expression and pathway enrichments. Drug combinations targeting candidate regulators of enriched pathways across our models were assessed in vivo in resistant PDXs. Drug trials were performed with n=5-7 mice per treatment arm until endpoint (tumour volume reaches 2000mm^3 or BW loss of 20%). Statistical analysis included t-tests for tumour volume and Wilcoxon test for survival. Results: 6 isogenic pairs of Eribulin acquired resistant TNBC PDX models were generated in vivo and molecular analysis was performed by comparing transcriptomic profiles of sensitive and resistant tumours. Pathway analysis revealed that, across 5 of 6 acquired resistant models, differentially expressed genes were significantly enriched for targets of SUZ12 (BH p-value&amp;lt;0.01). As SUZ12 makes up a core component of the PRC2 complex, we attempted to target EZH2, the catalytic component of PRC2, in vivo. Combining Tazemetostat, an FDA-approved EZH2 inhibitor, with Eribulin in one PDX model, resulted in tumor regression and improved overall survival (p&amp;lt;0.005) in one model. We will be testing this combination in more models, and performing differential chromatin accessibility studies to identify candidate driver genes in these regions. Conclusion: Our results suggest that combining an approved EZH2 inhibitor, Tazemetostat, with Eribulin can re-sensitize acquired-resistant TNBC PDXs to Eribulin. This approach could have significant clinical benefit in late stage hard to treat TNBCs. Citation Format: Kathryn Bozek, Cedric Darini, Cathy Lan, Marguerite Buchanan, Catherine Chabot, Josiane Lafleur, Juliet Guay, Eva Filosa, Adriana Aguilar-Mahecha, Mark Basik. EZH2 inhibition re-sensitizes drug resistant triple-negative breast cancer PDX models to Eribulin [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A045.

Abstract A163: Exoribonuclease XRN1 is a therapeutic vulnerability in tumors with intrinsically elevated type I interferon signaling

Abstract Background: 5′→3′ exoribonuclease 1 (XRN1) degrades single stranded mRNA from the 5′→3′ direction and plays a key role in endogenous cellular mRNA turnover. In addition, XRN1 can degrade double-stranded RNA (dsRNA), and as such plays a role in innate immunity by prevention of dsRNA accumulation and pPKR induction in virus-infected cells. We identified XRN1 as a putative selective vulnerability in tumor cells with intrinsic elevation of a Type I Interferon Stimulated Gene (TISG) signature through analysis of publicly available CRISPR screen data across 483 tumor cell lines. We further explored the role of XRN1 in a set of lung cancer cell lines with differential TISG expression in order to validate XRN1 as a compelling target for oncology drug development. Materials and Methods: NCI-H1650, NCI-H1703, NCI-H1944, and NCI-H838 lung adenocarcinoma cell lines were infected with lentiviruses containing Cas9 and sgRNAs targeting XRN1. Non-targeting sgRNAs were used as negative controls. XRN1 knockout (KO) cells and controls were evaluated in proliferation, apoptosis, qPCR and western blot assays. Results: Consistent with a selective dependency on XRN1 in cells with high intrinsic interferon signaling, XRN1 KO via CRISPR leads to robust anti-proliferative effects in TISG high NCI-H1650 and NCI-H1703 cells, but not in TISG low NCI-H838 and NCI-H1944 cells. Annexin V staining of NCI-H1650 cells upon XRN1 KO demonstrates that apoptosis is induced in TISG high cells. XRN1 KO in the TISG high setting leads to robust upregulation of Interferon-β mRNA consistent with activation of the MDA5 pathway by elevation of cytoplasmic dsRNA. Similarly, XRN1 loss induces pPKR activation in TISG high, but not TISG low cells. As pPKR activation triggers translational shutdown, TISG high selective pPKR elevation is consistent with the cell death observed. Exogenous treatment with Interferon-β or dsRNA mimetic Poly I:C to induce elevated Type I Interferon expression sensitizes NCI-H838 cells to XRN1 KO, with effects on cell proliferation. Conclusions: Taken together, these results demonstrate a critical role of XRN1 in cancer cells with intrinsically elevated Type I Interferon signaling. Cell death is triggered via accumulation of dsRNA and downstream activation of the MDA5 and PKR innate immune pathways. These data suggest that XRN1, through its regulation of dsRNA burden, is a compelling oncology target for TISG high tumors. Conflict of Interests: All authors are current or former employees and shareholders of Accent Therapeutics, Inc. Citation Format: Maureen M Lynes, Sophie A Shen, Sunaina P Nayak, Brian A Sparling, Scott Ribich, Stephen J Blakemore, Serena J Silver. Exoribonuclease XRN1 is a therapeutic vulnerability in tumors with intrinsically elevated type I interferon signaling [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A163.

HPR10 Added Benefit and Revenues of Oncology Drugs Approved By the European Medicines Agency between 1995 and 2020

HPR10 Added Benefit and Revenues of Oncology Drugs Approved By the European Medicines Agency between 1995 and 2020

MSR7 Incorporating External Data to Inform Overall Survival Extrapolation: A Review of NICE Health Technology Appraisals for Oncology Drugs

MSR7 Incorporating External Data to Inform Overall Survival Extrapolation: A Review of NICE Health Technology Appraisals for Oncology Drugs