The Christie School of Oncology: Christie Research Publications Repository
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Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: drug profile and expert opinion on the prevention and management of adverse events
No full textDiffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma in the United States and Western Europe and patients with relapsed or refractory (R/R) DLBCL who do not respond to salvage therapies have a poor prognosis. Loncastuximab tesirine (loncastuximab), a CD19-directed antibody-drug (pyrrolobenzodiazepine, PBD) conjugate approved as single agent for the third-line treatment of adult patients with R/R DLBCL and high-grade B-cell lymphoma, has shown durable clinical antitumor activity, including in difficult-to-treat subgroups. While loncastuximab has an overall manageable safety profile, it may cause drug-specific adverse events (AEs) different from other R/R DLBCL treatments. After summarizing the profile of loncastuximab, here we discuss PBD-specific AEs such as phototoxicity & cutaneous reactions, edema & effusions, and liver enzyme elevation; and use available clinical trial data, real-world evidence and clinical scenarios to provide expert opinion and practical advice on how to prevent and manage these non-hematological, PBD-specific AEs
Correction: Examining the Effectiveness of Electronic Patient-Reported Outcomes in People With Cancer: Systematic Review and Meta-Analysis
No full text[This corrects the article DOI: 10.2196/49089.]
Pregnancy associated breast cancer: an Australian perspective
No full textPregnancy associated breast cancer (PABC) is a relatively rare diagnosis, but with advancing maternal age at pregnancy, it is likely the number of cases will increase. The diagnosis and management of PABC is complex due to the need to balance the risk of optimal treatment of the mother with the potential fetal risks posed by prematurity and exposure to cancer treatment. In this article, we summarize the latest evidence for the diagnosis and surgical care of women with PABC within an Australasian context
Association between body composition and survival in gynecological cancer patients undergoing radiotherapy
No full textIntegrating electronic patient-reported outcome measures (ePROMs) into personalised follow-up for patients after radiotherapy. a feasibility study
No full textBACKGROUND: There is an unmet need in patient monitoring between the end of radiotherapy and the first follow-up appointment during which patients may experience severe side effects. Personalised follow-up has the potential to tailor healthcare to individual needs. ePROMs enable remote monitoring and identification of those needing earlier intervention. PURPOSE: To assess the feasibility of integrating ePROMs into personalised follow-up of patients after radiotherapy. MATERIALS AND METHODS: Patients with lung or head and neck (HN) cancer were enrolled. ePROMs questionnaires, comprising EQ-5D-5L and 14 lung or 19 HN cancer-specific questions adapted from CTCAE v5.0, were sent to patients at eight timepoints: pre-radiotherapy, mid-radiotherapy, end of radiotherapy, weekly for four weeks post-treatment, and first face-to-face follow-up appointment. Upon completion, automated advice was provided based on responses. Grade 2 or above symptoms were escalated to clinicians. Patient feedback was obtained through structured interviews. RESULTS: Over two months, 19 eligible patients (10 lung, 9 HN) were recruited: 13 received concurrent chemoradiotherapy, and six received radiotherapy alone. ePROMs completion rate was 69.1%, ranging from 47.4% to 89.5% at each timepoint. Three patients reported grade 3 or above symptoms on 5 instances during and after radiotherapy. Fourteen patients participated in the interviews: all 14 reported ePROMs were easy to complete, took an acceptable amount of time, and made them feel better supported. CONCLUSION: Integrating ePROMs into personalised follow-up is feasible and acceptable to patients. ePROMs provide insights into patients' symptoms during and after radiotherapy, highlighting the need for a tailored approach
Overlap of high-risk individuals across family history, genetic & non-genetic breast cancer risk models: Analysis of 180,398 women from European & Asian ancestries
No full textBACKGROUND: Breast cancer is multifactorial. Focusing on limited risk factors may miss high-risk individuals. METHODS: We assessed the performance and overlap of various risk factors in identifying high-risk individuals for invasive breast cancer (BrCa) and ductal carcinoma in situ (DCIS) in 161,849 European-ancestry and 18,549 Asian-ancestry women. Discriminatory ability was evaluated using the area under the receiver operating characteristic curve (AUC). High-risk criteria included: 5-year absolute risk ≥1·66% by the Gail model [GAIL(binary)]; first-degree family history of breast cancer [FH(binary)]; 5-year absolute risk ≥1·66% by a 313-variants polygenic risk score [PRS(binary)]; and carriers of pathogenic variants in breast cancer predisposition genes [PTV(binary)]. FINDINGS: The 5-year absolute risk by PRS outperformed the Gail model in predicting BrCa (Europeans(vs controls): AUC(PRS)=0·635 [0·632-0·638] vs AUC(Gail)=0·492 [0·489-0·495]; Asians(vs controls): AUC(PRS)=0·564 [0·556-0·573] vs AUC(Gail)=0·506 [0·497-0·514]). PRS(binary) and GAIL(binary) identified more high-risk European than Asia individuals. High-risk proportions were higher among BrCa (16-26%) and DCIS (20-33%) compared to controls (9-15%) among young Europeans and all Asians. Fewer than 7% of BrCa, 10% of DCIS, and 3% of controls were classified as high-risk by multiple risk classifiers. Overlap between PRS(binary) and PTV(binary) was minimal (<0·65% Europeans, <0·15% Asians) compared to the proportion at high risk using PTV(binary) alone (Europeans: 4·6%, Asians: 4·4%) and PRS(binary) alone (Europeans: 13·9%, Asians: 8·5%). PRS(binary) and FH(binary) uniquely identified 5-6% and 9-11% of young BrCa, respectively. INTERPRETATION: The incomplete overlap between high-risk individuals identified by PRS(binary), GAIL(binary), FH(binary,) and PTV(binary) highlights the need for a comprehensive approach to breast cancer risk prediction
Mezigdomide (MEZI) in novel combinations effectively reactivates immune system in patients with relapsed/refractory multiple myeloma (RRMM) including those after T-cell-redirecting therapies (TCRT)
No full textBody composition is associated with worse clinician-and patient-reported late radiotherapy-related toxicity in the REQUITE study
No full textDurvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study
No full textBACKGROUND & AIMS: At the TOPAZ-1 (NCT03875235) primary analysis, durvalumab plus gemcitabine and cisplatin (GemCis) significantly improved overall survival (OS) in advanced biliary tract cancer (aBTC). We report updated exploratory analyses of OS and safety, extended long-term survivors (eLTS), and subsequent anticancer therapy use. METHODS: Participants with aBTC received durvalumab+GemCis or placebo+GemCis every 3 weeks (≤8 cycles), then durvalumab or placebo monotherapy every 4 weeks until progressive disease or other discontinuation criteria were met. OS and serious adverse events were assessed in the full analysis and safety analysis sets, respectively. eLTS outcomes were assessed (full analysis set participants alive ≥30 months after randomisation). RESULTS: A total of 685 participants were randomised: durvalumab+GemCis (n = 341); placebo+GemCis (n = 344). After a median 41.3 (95% CI 39.3-44.1) months' follow-up in all participants, median OS (95% CI) for durvalumab+GemCis vs. placebo+GemCis was 12.9 (11.6-14.1) vs. 11.3 (10.1-12.5) months (hazard ratio, 0.74 [95% CI 0.63-0.87]); 36-month OS rate was 14.6% vs. 6.9%, respectively. In participants who achieved disease control (566/685; 82.6%), the 36-month OS rate was higher for durvalumab+GemCis (17.0%) vs. placebo+GemCis (7.6%). Overall, 12.8% were eLTS, with more eLTS in the durvalumab+GemCis (17.0%) vs. placebo+GemCis (8.7%) arms; eLTS included all clinically relevant subgroups. Durvalumab+GemCis improved OS regardless of subsequent anticancer therapy use. In eLTS, serious adverse events were comparable between arms and less frequent than in the full safety analysis set. CONCLUSIONS: Survival benefit and manageable safety continued with durvalumab+GemCis vs. placebo+GemCis approximately 3 years after the last participant was randomised. All clinically relevant subgroups were represented in eLTS, supporting standard-of-care status for durvalumab+GemCis in aBTC. IMPACT AND IMPLICATIONS: Durvalumab plus gemcitabine and cisplatin (GemCis) was approved for use in advanced biliary tract cancer (aBTC) after the primary analysis of the randomised, double-blind, phase III TOPAZ-1 study demonstrated that it significantly improved overall survival (OS) vs. placebo plus GemCis. This update, with analyses of OS and safety, extended long-term survivors, and subsequent anticancer therapy use, took place at a median follow-up of 41.3 months, which, to our knowledge, represents the longest follow-up to date in participants with aBTC. Survival benefit and manageable safety continued with durvalumab plus GemCis, all clinically relevant subgroups were represented in extended long-term survivors, and OS benefit with durvalumab plus GemCis was consistent regardless of subsequent anticancer therapy use. These long-term follow-up results support the standard-of-care status for durvalumab plus GemCis in aBTC, and enable physicians, patients and caregivers to make informed treatment decisions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03875235; https://clinicaltrials.gov/study/NCT03875235