Publication Practice Guidelines Research Articles

An Overview of the 2022 Update of Good Publication Practice (GPP) Guidelines: A Medical Writer’s Perspective

The Good Publication Practice (GPP) guidelines are a set of principles and recommendations pertaining to peer-reviewed or peer-orientated publications arising from research funded by or conducted in collaboration with industry sponsors, typically pharmaceutical, biotechnology, and medical device companies.
 This year marks the 20-year anniversary of the first GPP guidelines, which were published in 2003.1 These initial GPP guidelines were developed to promote transparency and to establish standards for publication practice used by pharmaceutical companies. Since then, GPP guidelines have undergone several updates to reflect changes within the publication field and to provide additional practical guidance on publication processes and procedures. These updates include GPP22 published in 2009 and GPP33 published in 2013. Good Practice for Conference Abstracts and Presentations (GPCAP)4 was published in 2019 to provide guidance specifically for congress abstract and presentations. The latest update of the GPP guidelines, the GPP 2022 update, was published in August 20225.

Good Publication Practice (GPP) 2022 Update: An Interview with Dikran Toroser

Dikran Toroser was educated in the UK and has a PhD in Biochemistry from Newcastle University in Newcastle upon Tyne. He did his post-doctoral research in the UK at the Cambridge lab on genetics and then moved to the US to work as a biochemist and researcher for the US Department of Agriculture (USDA). He has an extensive background in scientific publications as well as medical writing. He has led scientific publication teams involved with pre-clinical, clinical, and mature product studies and publications. Dikran is one of the founding faculty for the University of California San Diego medical writing certificate and a consulting director for the program. Active in professional organizations such as American Medical Writers Association (AMWA) and International Society for Medical Publication Professionals (ISMPP), Dikran most recently has been involved in compiling guidelines for the publication professionals, including the AMWA-EMWA-ISMPP joint position statement on the role of professional medical writers1 and GPP 2022, the latest 2022 update of Good Publication Practice (GPP) guidelines for company-sponsored biomedical research2.

Health care resource utilization and costs among individuals with vs without Huntington disease in a US population.

BACKGROUND: Quantifying the extent of health care resource utilization (HCRU) and costs associated with Huntington disease (HD) is vital for providers, decisionmakers, and payers to understand unmet treatment needs and to ensure limited resources can be used to benefit the maximum number of people with HD. OBJECTIVE: To quantify HCRU and costs for people with HD, overall and by disease stage, and compare these with non-HD controls. METHODS: This was a retrospective cohort study using administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases from January 1, 2009, to December 31, 2018. People with an HD claim between January 1, 2010, and December 31, 2017, were selected for this analysis and matched with non-HD controls for comparison. The HD cohort and the non-HD controls were exact matched on their follow-up duration and propensity score matched 1:4 to create the final analytical cohort. Index date was the first HD diagnosis for the HD cohort (proxy index date assigned to controls), and all individuals were required to have continuous enrollment for 12 or more months pre-index (baseline) and 3 or more months post-index. Proportions of all-cause HCRU (ie, outpatient visits, inpatient visits, emergency department visits, pharmacy fills, radiology visits, and physical/occupational therapy visits) in the 6-months post-index and HCRU counts and costs per patient per month (PPPM) over the entire follow-up were calculated for each cohort. RESULTS: A total of 2,473 individuals with HD and 9,522 matched non-HD controls were identified. HCRU in 6 months post-index was significantly greater in people with HD compared with non-HD controls for all health care service categories; P < 0.0001. The mean number of HCRU PPPM for all measured healthcare services was significantly higher in people with HD compared with non-HD controls (P < 0.001). Mean total costs (2018 USD PPPM) for the HD cohort ($2,260 [SD = $4,682]) were twice the total costs in the non-HD cohort ($1,056 [SD = $3,078]) (P < 0.0001) and were highest across all disease stages. CONCLUSIONS: This study provides current comprehensive HCRU and cost estimates in individuals with HD relative to those without the disease, thus demonstrating the high economic burden imposed by HD. DISCLOSURES: Dr Ta: Employment with Genentech (at time of study) and stock options with Roche; Dr To: Employment and stock options/dividends with Genentech; Dr Patel: Employment and stock options with Roche/Genentech; Dr Fuller: Employment with CHDI Management/CHDI Foundation; Mr Surinach: Employment with Genesis Research (which receives consulting fees from Genentech/Roche); Dr Abbass: Employment and stock options with Genentech; Dr Exuzides: Employment and stock options with Roche/Genentech; and Ms Luo: Employment with CHDI Management/CHDI Foundation. This study was funded by Genentech Inc. The authors thank Greg Rowe of Chrysalis Medical Communications for providing medical writing support, which was funded by F. Hoffmann-La Roche Ltd, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Patient perspectives on diagnosis and management of hidradenitis suppurativa: A web-based survey

Patient perspectives on diagnosis and management of hidradenitis suppurativa: A web-based survey

Annals for Educators - September 2022

Annals for Educators - September 2022

1779TiP Phase II clinical study evaluating the efficacy and safety of disitamab vedotin in patients (pts) with HER2-expressing urothelial carcinoma (RC48G001)

More than 212,000 deaths annually are related to bladder cancer worldwide (Sung 2021), with 5-year survival rates of <5% in metastatic urothelial carcinoma (UC) (Witjes 2021). Nearly half of all pts cannot tolerate standard cisplatin-based first line (1L) chemotherapy and opportunity still exists to improve outcomes in both 1L and later lines of therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in multiple malignant tumors and overexpression of HER2 may be associated with poor outcomes in UC (Zhao 2015). No HER2-directed therapies are currently approved for locally advanced unresectable or metastatic UC (LA/mUC). Disitamab vedotin (DV; RC48-ADC) is an investigational antibody–drug conjugate (ADC) comprised of a HER2-directed monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a protease-cleavable linker. DV elicits antitumor activity through MMAE-directed cytotoxicity and bystander effect (Li 2020). DV is conditionally approved in LA/mUC and gastric cancer in China and was granted Breakthrough Therapy designation by the FDA for second-line treatment of HER2-expressing LA/mUC after platinum-containing chemotherapy. RC48G001 (NCT04879329) is a phase 2, multicohort, open-label, multicenter trial to evaluate DV in pts with HER2-expressing LA/mUC. Pts are enrolled in 2 cohorts defined by HER2 expression (by immunohistochemistry [IHC]) and gene amplification (by in situ hybridization [ISH]) by central laboratory: Cohort A (IHC 3+, or 2+ and ISH+) and Cohort B (IHC 2+ and ISH-, or IHC 1+). Eligible pts must have measurable disease per RECIST v1.1, ECOG Performance Status of 0 or 1, and must have received 1 or 2 lines of prior systemic therapy, including 1 line of platinum-containing chemotherapy. The primary endpoint is confirmed objective response rate (ORR) assessed by blinded independent central review. Secondary endpoints include ORR assessed by investigator, duration of response, progression-free survival, disease control rate, overall survival, safety, and pharmacokinetic parameters. Enrollment for cohorts A and B is ongoing in North America and EU, and planned in LATAM, APAC, and Israel. NCT04879329. Under guidance of the authors, assistance in medical writing was provided by Hanna Thomsen, PhD, of Seagen Inc. and was funded by Seagen Inc. in accordance with Good Publication Practice (GPP3) guidelines. Seagen Inc.

Good Publication Practice (GPP) Guidelines for Company-Sponsored Biomedical Research: 2022 Update.

These updated Good Publication Practice (GPP) guidelines include recommendations for publishing company-sponsored biomedical research. The GPP guidelines apply to peer-reviewed or peer-oriented biomedical publications, such as manuscripts, meeting presentations, posters, and abstracts, as well as enhanced content, such as plain-language summaries. The current GPP guidelines incorporate guidance on ethics and transparency as well as the planning, development, review, and approval of biomedical publications and policies and procedures that describe these practices. Supplemental materials lay out processes for steering committees, publication plans, publication working groups, determining authorship, and documentation. Information about new topics, such as alliances and working with patients, has been included where appropriate within these supplemental materials. Incorporating the principles and best practices presented in these GPP guidelines will result in increased transparency and a firm ethical footing. This guidance is also intended to enable the compliant incorporation of new and emerging publication tools for the ethical publication of company-sponsored research.

P-156 MOUNTAINEER-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma: Trial in progress

Tucatinib (TUC), a highly selective HER2-directed tyrosine kinase inhibitor (TKI) approved in multiple regions for HER2+ metastatic breast cancer, is being developed as a novel therapy for patients with GI tumors including gastric or gastroesophageal junction adenocarcinoma (GEC). While trastuzumab (Tras) with chemotherapy is standard in the first-line setting for metastatic HER2+ GEC, no anti-HER2 therapy has demonstrated an OS benefit over chemotherapy as second-line therapy, possibly due to loss of HER2 expression following Tras-based therapy. In GEC xenograft models, dual targeting of HER2 with TUC and Tras showed superior activity to either agent alone. (Kulukian 2020) Interim results from the MOUNTAINEER study have shown promising activity for TUC and Tras for HER2+ mCRC.(Strickler 2019) The MOUNTAINEER-02 study (NCT04499924) is evaluating the efficacy and safety of TUC with Tras, ramucirumab (Ram), and paclitaxel (Pac) in patients with HER2+ GEC in the second-line setting. MOUNTAINEER-02 is a phase 2/3 study evaluating TUC + Tras with Ram and Pac. Eligible patients have locally-advanced unresectable or metastatic HER2+ GEC and have received a HER2-directed antibody and 1 prior line of therapy for advanced disease. Patients are ≥18 years of age; have an ECOG ≤1; and have had no prior exposure to Ram, an anti-HER2 or anti-EGFR TKI, HER2-directed antibody-drug conjugates, or taxanes ≤12 months before enrollment. Patients receive TUC 300 mg or placebo PO BID and Tras or placebo (IV on Days 1 and 15 of each 28-day cycle) in combination with Pac (IV on Days 1, 8, and 15) and Ram (IV on Days 1 and 15). The study includes an initial Pac-dose optimization stage because of the potential impact of TUC on Pac metabolism. The open-label phase 2 part determines the recommended dose of Pac (60 or 80 mg/m2) combined with TUC, Tras, and Ram in 6–18 patients and evaluates safety and activity of the regimen in Cohorts 2A and 2B (30 patients each). The randomized, double-blind, phase 3 part compares the efficacy and safety of TUC and Tras (Arm 3A, ∼235 patients) vs placebo (Arm 3B, ∼235 patients), both in combination with Ram and Pac, and evaluates activity of TUC with Ram and Pac (Arm 3C, ∼30 patients). The coprimary phase 3 endpoints are OS and PFS per investigator, and secondary endpoints include DOR, confirmed ORR, and DCR. Secondary objectives include patient-reported outcomes. HER2 status is determined by blood-based NGS assay or IHC/ISH assay of a tumor tissue sample (IHC3+ or IHC2+/ISH+) at screening. In Cohort 2A and phase 3, patients must be HER2+ by blood-based NGS. In Cohort 2B, patients must be HER2+ by biopsy but HER2 negative by blood-based NGS after progression in first-line or subsequent therapy. Disease assessments per RECIST v1.1 occur q6 weeks for 36 weeks, then q9 weeks. The pharmacokinetics of TUC, Pac, and their metabolites are evaluated in a subset of patients, including a cohort with gastrectomies. Enrollment in phase 2 is ongoing. NCT04499924. The authors thank Joseph Giaconia of MMS Holdings, Michigan, USA for providing medical writing support/editorial support, which was funded by Seagen Inc., Bothell, WA, USA in accordance with Good Publication Practice (GPP3) guidelines. Seagen Inc.

OP0023 A RANDOMIZED, DOUBLE-BLIND TRIAL COMPARING SECUKINUMAB 300 MG AND 150 MG AT WEEK 52 IN PATIENTS WITH ANKYLOSING SPONDYLITIS WHO DID NOT ACHIEVE INACTIVE DISEASE DURING AN INITIAL 16 WEEKS OF OPEN-LABEL TREATMENT WITH SECUKINUMAB 150 MG

OP0023 A RANDOMIZED, DOUBLE-BLIND TRIAL COMPARING SECUKINUMAB 300 MG AND 150 MG AT WEEK 52 IN PATIENTS WITH ANKYLOSING SPONDYLITIS WHO DID NOT ACHIEVE INACTIVE DISEASE DURING AN INITIAL 16 WEEKS OF OPEN-LABEL TREATMENT WITH SECUKINUMAB 150 MG

A case of normal C1 esterase inhibitor hereditary angioedema successfully treated with berotralstat

A case of normal C1 esterase inhibitor hereditary angioedema successfully treated with berotralstat

AMWA, EMWA, and ISMPP Promote Ethical, Professional Medical Writing in JAMA Oncology Letter to the Editor

In March 2021, Del Paggio et al. published an article in JAMA Oncology that included disparaging comments about medical writers. American Medical Writers Association (AMWA) leaders, in partnership with representatives from the European Medical Writers Association (EMWA) and the International Society for Medical Publication Professionals (ISMPP), immediately and swiftly drafted and submitted a letter of response to this article, which was published on August 26, 2021, along with 2 other letters and the authors‘ response to all 3 letters. Del Paggio et al.’s article reported on multiple aspects of randomized clinical trials in oncology, including the use of professional medical writers. Specifically, the authors stated, “There is reason to be concerned that medical writers may unduly influence the interpretation of trials, … as it is unlikely that medical writers have a neutral effect on the clinical trial reporting.” Although we all share an understanding of the value of medical writers, it is imperative that we respond publicly to these attacks to safeguard the reputation of our profession. As highlighted in our letter, the use of our profession’s expertise improves accuracy, timeliness, and adherence to ethical conduct. Evidence from independent research on the benefits of working with medical writers was included in the response. The commitment of medical writers to adhere to Good Publication Practice (GPP3) guidelines and to ethical principles in scientific publishing as well as to the professional codes of conduct of their professional organizations was also identified as a significant benefit of working with professional medical writers.

Effectiveness of Sodium Zirconium Cyclosilicate in Hemodialysis Patients With Severe Hyperkalemia

Effectiveness of Sodium Zirconium Cyclosilicate in Hemodialysis Patients With Severe Hyperkalemia

Economic impact of abrocitinib monotherapy and combination therapy in patients with moderate-to-severe atopic dermatitis: Results from JADE MONO-2 and JADE COMPARE

Economic impact of abrocitinib monotherapy and combination therapy in patients with moderate-to-severe atopic dermatitis: Results from JADE MONO-2 and JADE COMPARE

FRI0271 IMPACT OF HLA-B27 STATUS ON CLINICAL OUTCOMES AMONG PATIENTS WITH ANKYLOSING SPONDYLITIS TREATED WITH SECUKINUMAB

Background:Ankylosing spondylitis (AS) is strongly associated with the genetic marker HLA-B27. Approximately 80%-90% of white patients with AS express HLA-B27 compared with &lt; 8% of the general population. In patients with AS, negative HLA-B27 status is a predictor of worse response to TNFis.1The impact of HLA-B27 status on clinical efficacy of secukinumab, a fully human monoclonal antibody that selectively inhibits IL-17A, has not been studied.Objectives:To analyze the impact of HLA-B27 status on clinical outcomes at Week 16 in patients with AS treated with secukinumab vs placebo.Methods:Patients with AS were pooled from the MEASURE 1-4 studies (NCT01358175,NCT01649375,NCT02008916, andNCT02159053) and stratified by HLA-B27 status. All trials included patients who received secukinumab 150 mg every 4 weeks with or without an initial loading dose (10 mg/kg IV at Weeks 0, 2, 4 or 150 mg SC at Weeks 0, 1, 2, and 3) or placebo control. MEASURE 3 included patients receiving secukinumab 300 mg every 4 weeks following the initial IV loading dose. Efficacy at Week 16 was determined by the proportion of patients achieving ASAS20/40, ASAS5/6, ASAS partial remission, BASDAI50, ASDAS-CRP &lt; 2.1, ASDAS-CRP &lt; 1.3, and improvement in Patient Global Assessment (VAS) and total spinal/back pain (VAS) scores. In MEASURE 1, 2, and 4, quality of life (QOL) was assessed at Week 16 by the SF-36 PCS, SF-36 MCS, and ASQOL. ASAS, BASDAI, and ASDAS-CRP responses were analyzed by nonresponder imputation, and all other outcomes by mixed models for repeated measures. For hypothesis generation, outcomes at Week 16 with secukinumab vs placebo within HLA-B27 strata were compared by logistic regression analysis without adjustment for multiple comparisons.Results:Baseline characteristics were balanced across treatment groups, although more HLA-B27+ patients than HLA-B27− patients were male (71%-73% vs 43%-50%). HLA-B27+ patients receiving any dose of secukinumab were significantly more likely to achieve ASAS, BASDAI50, and ASDAS-CRP responses vs those receiving placebo (P&lt; .05; Figure 1). HLA-B27− patients receiving secukinumab 300 mg were significantly more likely to achieve ASAS40, ASAS partial remission (Figure 1A), and BASDAI50 (Figure 1B) responses than those receiving placebo (P&lt; .05). Patients receiving any dose of secukinumab were more likely to achieve ASAS5/6 and ASDAS-CRP &lt; 2.1 than those receiving placebo, regardless of HLA-B27 status (P&lt; .05; Figure 1B). All secukinumab-treated patients experienced significant improvement in Patient Global Assessment at Week 16 vs placebo, regardless of HLA-B27 status, while only HLA-B27+ patients experienced significant reduction in total spinal/back pain vs placebo (P&lt; .05; Figure 2A). Numerical improvements in QOL were observed in all patients receiving secukinumab 150 mg vs placebo; these reached significance for HLA-B27+ patients (Figure 2B).Conclusion:Secukinumab is effective in patients with AS regardless of HLA-B27 status; HLA-B27+ patients may derive increased therapeutic benefit compared with HLA-B27− patients.Reference:[1]Alazmi M, et al.Arthritis Care Res (Hoboken). 2018;70:1393-9.Acknowledgments:This study was funded by Novartis Pharmaceuticals Corporation. The authors thank Rich Karpowicz, PhD, of Health Interactions, Inc, for providing medical writing support/editorial support, which was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).Disclosure of Interests:Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Renato Calheiros Shareholder of: Novartis, Employee of: Novartis, Xiangyi Meng Shareholder of: Novartis, Employee of: Novartis, Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Marina Magrey Grant/research support from: AbbVie, Amgen, and UCB, Consultant of: Eli Lilly and Novartis

THU0162 LIKELIHOOD OF CLINICAL WORSENING AMONG RHEUMATOID ARTHRITIS PATIENTS WHO ACHIEVED A PARTIAL RESPONSE TO ADALIMUMAB AND WERE SUBSEQUENTLY SWITCHED TO SARILUMAB

Background: Rheumatoid arthritis (RA) patients who achieve a response to therapy but fail to reach low disease activity (LDA) or remission (partial responders) may decline treatment changes for fear of clinical worsening and losing their achieved response. Little is known about the likelihood of worsening after switching therapy in partial responders, and this limits patients’ ability to make informed treatment decisions. Objectives: This post hoc analysis of the open-label extension (OLE) of MONARCH (NCT02332590) assesses the effects of switching from adalimumab to sarilumab in patients with RA who achieved a partial response to adalimumab but not remission or LDA. Methods: MONARCH was a 24-week, head-to-head monotherapy trial comparing sarilumab with adalimumab. At study end, patients randomized to adalimumab were switched to sarilumab 200 mg q2w for the OLE. Partial responders to adalimumab were defined as patients who had improved more than the minimal clinically important difference (MCID) in the Clinical Disease Activity Index (CDAI) during MONARCH, but who continued to have moderate to high disease activity (CDAI >10) at OLE baseline (BL). MCID was defined as a CDAI decrease ≥12 from a BL CDAI >22 or ≥6 from a BL CDAI >10 to ≤22. Response following treatment switch was assessed by change in CDAI and other outcomes from OLE BL to OLE Week 24. The effect of switching was analyzed descriptively and categorized: worsening = CDAI increase ≥6; improvement = CDAI decrease ≥6; stable = CDAI absolute change Results: Of 369 patients enrolled in MONARCH, 320 (87%) entered the OLE; 155 were switched from adalimumab to sarilumab, and of these, 91 were partial responders, who had a mean (SE) CDAI at OLE BL of 19.56 (0.86). Mean (SE) improvement in CDAI from OLE BL to OLE Week 24 in these patients was 7.37 (1.10). At OLE Week 24, only 6% of adalimumab partial responders had worsened after switching to sarilumab, while 57% had improved; the remaining 37% maintained stable disease activity. Analyses of other efficacy measures—patient and physician global assessments, disease activity score 28-joint erythrocyte sedimentation rate, and swollen and tender joint counts—demonstrated similar results: improvement was seen in 27–78% and worsening in 2–17%. No new safety signals emerged during the OLE. The adverse event profile among patients switching from adalimumab to sarilumab was consistent with the established safety profile of sarilumab. Conclusion: Among adalimumab CDAI partial responders who switched to sarilumab, there was a low likelihood of clinical worsening, while more than half of such patients achieved clinically meaningful improvement. Similar results were observed for other efficacy measures. This small risk of worsening coupled with the substantial likelihood of improvement after switch may help alleviate patients’ concerns around loss of response and help inform shared decision-making. Acknowledgments: Study funding and medical writing support (Gregory Bezkorovainy, Adelphi Communications, New York) were provided by Sanofi Genzyme (Cambridge, USA) and Regeneron Pharmaceuticals, Inc. (Tarrytown, USA) in accordance with Good Publication Practice (GPP3) guidelines. Amy Praestgaard (Sanofi Genzyme employee) contributed to the statistical analysis for this abstract. Disclosure of Interests: Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Gerd Rudiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Kerri Ford Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, Hubert van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, Henry Leher Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Karthinathan Thangavelu Shareholder of: Sanofi Genzyme, Employee of: EMD Serono, Sanofi Genzyme, Vivian Bykerk: None declared

LBA2 First-line durvalumab plus platinum-etoposide in extensive-stage (ES)-SCLC: Safety, pharmacokinetics (PK) and immunogenicity in CASPIAN

LBA2 First-line durvalumab plus platinum-etoposide in extensive-stage (ES)-SCLC: Safety, pharmacokinetics (PK) and immunogenicity in CASPIAN

474O - Efficacy and safety of first-line durvalumab (D) ± tremelimumab (T) vs chemotherapy (CT) in Asian patients with metastatic NSCLC: Results from MYSTIC

474O - Efficacy and safety of first-line durvalumab (D) ± tremelimumab (T) vs chemotherapy (CT) in Asian patients with metastatic NSCLC: Results from MYSTIC

322P - Three-year overall survival update from the PACIFIC trial

322P - Three-year overall survival update from the PACIFIC trial

201P - Efficacy and safety of darolutamide in non-metastatic castration-resistant prostate cancer (nmCRPC) in the ARAMIS trial

Abstract Background Asymptomatic nmCRPC patients (pts) would benefit from treatments (Tx) that delay disease progression and maintain quality of life (QoL), with minimal Tx-related adverse events (AEs). In ARAMIS, darolutamide (DARO) prolonged metastasis-free survival vs placebo (PBO) (40 vs 18 months; HR 0.41; 95% CI 0.34–0.50; P Methods Pts were randomized to DARO 600 mg twice daily (n = 955) or PBO (n = 554), while androgen deprivation therapy continued in both arms. Secondary/exploratory endpoints included safety, time to cytotoxic chemotherapy, time to antineoplastic therapy, time to PSA progression, and QoL. Results DARO substantially delayed times to PSA progression (33 vs 7 months; HR 0.13; 95% CI 0.11–0.16; P 10% of pts. Discontinuation rates due to AEs were 8.9% with DARO and 8.7% with PBO. AEs noted with other androgen receptor inhibitors (including fracture, falls, seizures, hypertension and cognitive disorder) showed minimal or no difference in incidence between groups. DARO maintained QoL, and delayed the onset of pain and disease-related urinary symptoms compared with PBO. Conclusions DARO delays disease progression and subsequent Tx for metastatic castration-resistant prostate cancer vs PBO, maintaining QoL without increasing incidence of key AEs. Clinical trial identification NCT02200614. Editorial acknowledgement Medical writing support for the development of this abstract was provided by Lucy Smithers, PhD, and editorial support, including formatting, proofreading, and submission was provided by Beth King, both of Scion Medica, London, supported by Bayer according to Good Publication Practice guidelines. Legal entity responsible for the study Orion Corporation, Orion Pharma and Bayer AG. Funding Orion Corporation and Bayer AG. Disclosure J.S-T. Pang: Non-remunerated activity/ies, Writing support: Bayer. N. Shore: Advisory / Consultancy, Research grant / Funding (self): Ferring; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Research grant / Funding (self): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Dendreon; Advisory / Consultancy, Research grant / Funding (self): Tolmar; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (self): Myovant Sciences; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Research grant / Funding (self): BMS; Advisory / Consultancy, Research grant / Funding (self): Nymox. M.R. Smith: Honoraria (self): Amgen; Honoraria (self): Astellas; Honoraria (self): Bayer; Honoraria (self): Clovis; Honoraria (self): Gilead; Honoraria (self): Janssen; Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Pfizer. T.L. Tammela: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (self): Lidds AB; Advisory / Consultancy, Research grant / Funding (self): Astellas. E. Vjaters: Research grant / Funding (self): Ipsen; Research grant / Funding (self): Bayer; Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Orion. M. Jievaltas: Honoraria (self): Bayer; Honoraria (self): Ipsen; Honoraria (self): Janssen. M. Luz: Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Research grant / Funding (self): Janssen; Research grant / Funding (self): AstraZeneca; Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (self): Ferring; Speaker Bureau / Expert testimony: Sanofi. B. Alekseev: Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Bayer; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Astellas; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: BMS; Honoraria (self), Non-remunerated activity/ies: Ferring; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Janssen; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: MSD; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Pfizer; Research grant / Funding (self), Non-remunerated activity/ies: Sanofi. I. Kuss: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bayer. M-A. Le Berre: Full / Part-time employment: Bayer Healthcare. A. Snapir: Full / Part-time employment: Orion Pharma. T. Sarapohja: Full / Part-time employment: Orion Corporation. K. Fizazi: Honoraria (self), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self): Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Curevac; Advisory / Consultancy: ESSA; Advisory / Consultancy: Orion Pharma; Advisory / Consultancy: Roche/Genentech. All other authors have declared no conflicts of interest.

131P - Cabozantinib in Asian patients with hepatocellular carcinoma and other solid tumours: Population pharmacokinetics analysis

BackgroundCabozantinib, an inhibitor of MET, AXL and VEGF receptors, was recently approved for the treatment of patients with advanced hepatocellular carcinoma (HCC) who had previously received sorafenib, based on findings of the CELESTIAL trial. We previously reported cabozantinib pharmacokinetics (PK) data based on 9 cabozantinib studies (N = 1534), Here, we report updated cabozantinib PK data in Asian and non-Asian ethnicities including patients with HCC. MethodsWe used data from ten cabozantinib studies that included healthy volunteers (HV) and patients with various cancer types (HCC, renal cell carcinoma, castration-resistant prostate cancer, medullary thyroid cancer [MTC], and glioblastoma multiforme). Studies pertinent to HCC were the CELESTIAL trial (NCT01908426) and the HCC cohort of a phase 2 trial (NCT00940225). The impact on PK parameters of selected covariates (age, weight, sex, race, cancer type, formulation, and liver dysfunction according to the National Cancer Institute Organ Dysfunction Working Group [NCI-ODWG]) was evaluated. Steady-state PK parameters were predicted for Asian and non-Asian patients. ResultsData from 2023 individuals were included (cancer patients, n = 1883; HV, n = 140), of whom 211 were of Asian ethnicity and 1812 of non-Asian ethnicity. MTC cancer type had the largest effect on cabozantinib PK parameters, with a 90% increase in apparent clearance (CL/F) relative to HV. Other cancer types, including HCC, and liver dysfunction per NCI-ODWG did not impact cabozantinib PK. However, because CELESTIAL excluded patients with Child-Pugh scores of B or C, results on patients with more compromised liver function are limited. A 24% decrease in CL/F was observed in females; Asian ethnicity, age, and weight had no clinically significant impact on cabozantinib clearance. ConclusionsMinimal cabozantinib PK and predicted exposure differences were observed across various cancer types except for MTC. The PK of cabozantinib was similar in individuals of Asian and non-Asian ethnicity. These findings are consistent with the major metabolic pathway of cabozantinib via cytochrome P450 3A4 which is not prone to genetic polymorphism. Editorial acknowledgementThe authors thank Isabelle Kaufmann, PhD of Oxford PharmaGenesis, Oxford, UK for providing medical writing support, which was sponsored by Ipsen, Abingdon, UK in accordance with Good Publication Practice guidelines. Legal entity responsible for the studyIpsen. FundingIpsen. DisclosureC-H. Hsu: Research grant/Funding (self): Ipsen; Honoraria (self): Ipsen. L. Nguyen: Full / Part-time employment: Exelixis. A-L. Cheng: Honoraria (self): Bayer; Honoraria (self): Eisai; Honoraria (self): Merck Sharp Dohme; Honoraria (self): Merck Serono; Honoraria (self): Novartis; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Roche/Genentech; Honoraria (self): IQVIA. Advisory/Consultancy: Bayer Schering Pharma; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Eisai; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ono Pharmaceutical; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Nucleix Ltd.; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: IQVIA. Speaker Bureau/Expert testimony: Bayer Yakuhin, Ltd.; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Amgen Taiwan. Travel/Accommodation/Expenses: Bayer Yakuhin, Ltd.; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Ono Pharmaceutical; Travel/Accommodation/Expenses: Roche/Genentech; Travel/Accommodation/Expenses: IQVIA. T.X.Q. Nguyen: Full / Part-time employment: Ipsen. K. Brendel: Full / Part-time employment: Ipsen. V. Aslanis: Full / Part-time employment: Ipsen. F. Benzaghou: Full / Part-time employment: Ipsen.