Systemic Anticancer Treatment Research Articles

Hospital Factors Influencing the Mobility of Patients for Systemic Therapies in Breast and Bowel Cancer in the Metastatic Setting: A National Population-based Evaluation

AimsThis national study investigated hospital quality and patient factors associated with treatment location for systemic anticancer treatment (SACT) in patients with metastatic cancers. Materials and methodsUsing linked administrative datasets from the English NHS, we identified all patients diagnosed with metastatic breast and bowel cancer between 1 January 2016 and 31 December 2018, who subsequently received SACT within 4 months from diagnosis. The extent to which patients bypassed their nearest hospital was investigated using a geographic information system (ArcGIS). Conditional logistic regression models were used to estimate the impact of travel time, hospital quality and patient characteristics on where patients underwent SACT. Results541 of 2,364 women (22.9%) diagnosed with metastatic breast cancer, and 2,809 of 10,050 (28.0%) patients diagnosed with metastatic bowel cancer bypassed their nearest hospital providing SACT. There was a strong preference for receiving treatment at hospitals near where patients lived (p < 0.001). However, patients who were younger (p = 0.043 for breast cancer; p < 0.001 for bowel cancer) or from rural areas (p = 0.001 for breast cancer; p < 0.001 for bowel cancer) were more likely to travel to more distant hospitals. Patients diagnosed with rectal cancer were more likely to travel further for SACT than patients with colon cancer (p = 0.002). Patients were more likely to travel to comprehensive cancer centres (p = 0.019 for bowel cancer) and designated Experimental Cancer Medicine Centres (ECMCs) although the latter association was not significant. Patients were less likely to receive SACT in hospitals with the highest readmission rates (p = 0.046 for bowel cancer). ConclusionPatients with metastatic cancer receiving primary SACT are prepared to travel to alternative more distant hospitals for treatment with a preference for larger comprehensive centres providing multimodal care or hospitals which offer early phase cancer clinical trials.

The role of integrating palliative care with systemic anticancer treatment at end-of-life: A single center experience.

e24067 Background: This study examines the utilization of systemic anticancer treatments, including chemotherapy, targeted therapy, and immunotherapy, in advanced cancer patients. Specifically, it aims to underscore the impact of integrating palliative care in the administration of anticancer treatment during the last months of life. Methods: A retrospective chart review of patients who received chemotherapy, targeted therapy, and immunotherapy at Ramathibodi Hospital and passed away between January 1, 2019, and December 31, 2022. Demographic data, cancer type, modality, intent, and route of anticancer therapy, as well as health scheme and referral to palliative care services, were collected. Information regarding systemic anticancer treatments administered at 2 weeks, 1 month, 3 months, and 6 months preceding death underwent thorough analysis. Logistic regression was employed to assess odds ratios (OR) and 95% CIs for factors influencing decision-making regarding anticancer treatments. Results: Among the 542 deceased patients, 378 had received anticancer treatments within the last 6 months of life. The distribution of anticancer treatments categorized by timing—6 months, 3 months, 1 month, and 2 weeks before death—was 378 (69.7%), 388 (71.6%), 206 (38.0%), and 129 (23.8%), respectively. Older adults constituted nearly half of the population (45.2%). The utilization of anticancer treatments, particularly in the realms of targeted therapy and immunotherapy, at the terminal stages of life is showing a discernible upward trend. Palliative care consultations were present in 26.9% of cases during cancer care. The presence of palliative care consultation was significantly associated with lower odds ratios of receiving end-of-life anticancer treatments at 2 weeks and 1 month before death (OR: 0.55 [95% CI: 0.33 to 0.89], p = 0.016 and 0.54 [95% CI: 0.36 to 0.85], p = 0.004, respectively). Specifically, integrating palliative care reduced the use of chemotherapy in treatment at 2 weeks and 1 month before death (OR: 0.51 [95% CI: 0.27 to 0.98], p = 0.042 and OR: 0.55 [95% CI: 0.33 to 0.90], p = 0.019, respectively). However, the data showed a decrease in the number of patients; nonetheless, no statistically significant differences were observed in the utilization of targeted therapy and immunotherapy. In our analysis, we examine the factors influencing the utilization of anticancer treatments, reveal that there were no significant differences observed among other factors, including age, cancer type, and health scheme. Conclusions: Integration of palliative care into oncology services significantly correlated with a reduced risk of receiving anticancer treatments, particularly chemotherapy, within the last 30 days of life for advanced cancer patients. Insufficient evidence exists to ascertain the impact of palliative care on the utilization of targeted therapy and immunotherapy.

Single institution analysis of glioblastoma multiforme (GBM) outcomes based on year of diagnosis: A 17 year review.

e14023 Background: GBM is the most common brain tumour in adults. The latest WHO classification excludes IDH mutated tumours, acknowledging their favourable prognosis. MGMT methylation is a prognostic biomarker and predicts level of benefit from Temozolomide. The standard of care management includes maximal surgical resection followed by radiotherapy with concurrent and adjuvant Temozolomide. This has remained largely unchanged for nearly 20 years. We analysed 17 years of newly diagnosed GBM cases attending Medical Oncology at our institution to assess outcome advancements. Methods: Demographic information, clinicopathological characteristics, surgery, radiotherapy and systemic anti-cancer treatment data were collected from the charts of patients diagnosed with GBM and seen by the Medical Oncology department at Cork University Hospital between 2005-2021. The study population was divided into 2 time periods: 2005-2016 and 2017-2021. Overall survival was recorded. Baseline characteristics was compared across time periods using the Chi-Square test. Univariate and multivariate analysis was performed to assess impact of different variables on overall survival. Results: The analysis comprised 306 patients, with 142 and 164 diagnosed between 2005-2016 and 2017-2021 respectively. Median age was 62 years (range 17-86) and patients were predominantly male (65%). Patients in the earlier time period were more likely to have ECOG performance status 0-1 (80% vs 65% p = 0.011) and were more likely to commence treatment on Stupp protocol (99% vs 80% p = &lt;0.001). IDH and MGMT testing were less prevalent in the earlier time period. Median overall survival (mOS) for the entire cohort was 11.6 months. Univariate analysis revealed correlations between overall survival and time period of diagnosis, age &gt;65, MGMT status, ECOG performance status, steroid use, surgery, re-resection, and completion of adjuvant chemoradiation protocols. The mOS was 12.3 months in the earlier time period and 10.4 months in the later time period (HR = 1.35 p = 0.012). Time period of diagnosis remained an independent prognostic factor for poor outcome on multivariate analysis. Notably, mOS during the COVID-19 pandemic (2020-2021) was 10.6 months, showing no difference from other time periods. Conclusions: Despite advances in our knowledge regarding the molecular biology of GBM, prognosis remains poor. Our institution’s 17 year survival data indicates no improvement over time emphasising the urgent need for new treatment strategies. Notably, the more recent time period had an increased number of frailer patients who were too unwell to commence any adjuvant treatment, possibly indicating a lower referral threshold which may have negatively impacted mOS in that cohort. Additionally, the absence of IDH status assessment in the earlier era means some IDH mutant patients were likely included, thereby inflating the mOS for that cohort.

Neoadjuvant toripalimab plus chemotherapy for resectable stage II-IIIB non-squamous non-small cell lung cancer with EGFR mutations: A multi-center, multi-cohort, exploratory study.

TPS8120 Background: Neoadjuvant immunotherapy has been widely applied in the treatment of resectable stage II-IIIB NSCLC patients without driver gene mutation. However, as for the EGFR-positive patients, the therapeutic effect of neoadjuvant treatment, either TKI or chemotherapy, is far from satisfied and the outcome of neoadjuvant immunotherapy plus chemotherapy in these patients remains an unanswered but crucial question. Herein, we conducted a phase 2 prospective trial (NCT05962021). Methods: This is a multicenter, multi-cohort prospective phase 2 study in the treatment-naïve patients with resectable stage II-IIIB (N2) (AJCC 8th edition) non-squamous NSCLC harboring EGFR mutations (19DEL or L858R). Enrolled patients will be divided into two cohorts according to EGFR status and receive neoadjuvant toripalimab (240mg, q3w) plus platinum-based doublet chemotherapy (pemetrexed 500mg/m2 plus carboplatin AUC 5, q3w) for 3 cycles. Surgery will be performed after completion of neoadjuvant therapy based on the multidisciplinary discussion, while local radiotherapy will be considered if the patient cannot undergo surgery due to disease progression. Key inclusion criteria: non-squamous NSCLC, resectable stage II-IIIB (N2), EGFR mutations (19DEL or L858R), age≥18 years, ECOG PS 0-1 and adequate cardiopulmonary function. Exclusion criteria: prior systemic anticancer treatment, contraindication to immunotherapy, active autoimmune disease. Adequate pre-treatment tissue samples are required for RT-PCR or next-generation sequencing to determine the EGFR mutation status and PD-L1 expression immunohistochemical detection. The primary study endpoint is complete pathological response (pCR) rate, per blinded independent pathologist review. Simon's optimal two-stage design will be used to test the null hypothesis of pCR rate ≤5% and alternative hypothesis of pCR rate ≥15%, and 5 or more pCRs among 56 patients per arm are needed for the primary endpoint to be met. Secondary endpoints include major pathological response (MPR) rate, pCR/MPR rate in different EGFR mutation subgroups (19DEL or L858R) and different PD-L1 expression subgroups (TPS &lt; 1% and ≥ 1%), event-free survival and safety and tolerability. Peripheral blood, stool and tissue samples will be obtained longitudinally at baseline, during perioperation and at follow-ups for exploratory analysis. Clinical trial information: NCT05962021 .

Patient-Reported Experiences of Supportive Cancer Care during the COVID-19 Pandemic

Background. During the COVID-19 pandemic, people affected by cancer were in need of information about the virus and about the (self-) management of cancer symptoms and treatment. It is important to understand how patients with cancer navigated through the pandemic and to explore their experience relating to their supportive care needs. Aim. This study aimed to describe the experience of Swiss oncological patients during the COVID-19 pandemic with additional supportive cancer care. Methods. A single-center study was conducted in 2021. Patients with melanoma, breast, lung, or colon cancer who received active systemic anticancer treatment at the time of the COVID-19 pandemic and who were additionally seeing either oncology clinical nurse specialists, integrative medicine physicians, or both were included. We conducted semistructured interviews alongside the patient-reported quantitative assessment of distress and resilience. Thematic analysis was performed for the qualitative data and descriptive statistics for the quantitative data. Results. Eighteen patients with cancer were interviewed. Patients seeing an integrative medicine physician highlighted that they positively felt being addressed as a whole person during the consultations. The oncology clinical nurse specialists were perceived as the first point of contact for the patients and had more time during the pandemic compared to what the patients normally received. In general, patients did not experience delays or disruptions in their cancer treatment. As immunosuppressed and fatigued patients with cancer, they felt supported by the restrictions and hygienic measures. Access to vaccination reassured patients against the risk of infection. These results were reflected in the quantitative data, as we found moderate distress levels (M = 4.1; SD = 2.5) and high resilience scores (M = 7.5; SD = 0.9) in this patient population. Conclusion. During the COVID-19 pandemic, patients with cancer felt particularly supported by integrative medicine and cancer nurse consultations. Secured resources for nursing consultations and integrative medicine services can help to address the supportive care needs of patients with cancer.

Insights for clinical management from the real-life data of the centralized West of Scotland biliary cancer clinic.

With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence approvals, it is as important as ever to have real-life data in national populations. We performed an audit of the first 2 year-activity (Sep 2019-Sep 2021) of the centralized West-of-Scotland-BTC clinic. 122 patients accessed the service, including 68% with cholangiocarcinoma (CCA), 27% with gallbladder cancer (GBC), and 5% with ampulla of Vater carcinoma with biliary phenotype (AVC). Median age at diagnosis was 66 (28-84), with 30% of newly diagnosed patients being younger than 60 years-old. Thirty-five cases (29%) underwent surgery, followed by adjuvant-chemotherapy in 66%. 60% had recurrent disease (80% with distant relapse). Sixty-four patients (58%) started first-line Systemic-AntiCancer-Treatment (SACT). Of these, 37% received second line SACT, the majority of which had iCCA and GBC. Thirty-% of those who progressed received third line SACT. About 30% of BTC were eligible for curative surgery. Fifty-eight and twenty% of the overall cohort of advanced BTC patients received first and second line SACT. Our data suggest that reflex genomic profiling may not be cost-effective until molecularly driven strategies are limited to second line setting.

Evaluation of patient satisfaction of receiving Systemic Anti-Cancer Therapy prescribed by nurse Non-Medical Prescribers

PurposeTo evaluate patient satisfaction of patients receiving Systemic Anti-Cancer Treatment prescribed by nurse Non-Medical Prescribers as a new model of care at a Cancer Unit in Northern Ireland, United Kingdom. MethodsA cross-sectional survey design, with a convenience sample of patients from five tumour groups who received Systemic Anti-Cancer Therapy by nurse Non-Medical Prescribers, across a 3-month period in 2022 was employed. Anonymised data were collected via postal survey, which incorporated a minimally modified version of the 45-item Leeds Satisfaction Questionnaire (LSQ). ResultsOne-hundred and sixteen surveys were returned, yielding a 36% response rate. Overall patients’ satisfaction levels with nurse non-medical prescribing of systemic anti-cancer therapy were high across all six subscales of the modified LSQ corroborated by qualitative free-text comments. Eighty-five percent of participants indicated they were happy to continue being prescribed systemic anti-cancer therapy by the nurse non-medical prescribers. ConclusionOverall patient satisfaction of Systemic Anti-Cancer Treatment prescribed by nurse Non-Medical Prescribers was positively rated; with high standards of compassionate, person-centred care reported, demonstrating an acceptable transformation in care delivery from a consultant-led model. Nonetheless, there was scope for improved health literacy to enhance patients’ understanding and compliance with treatment.

Palliative care integration and end-of-life care intensity for patients with NSCLC

BackgroundNon-small cell lung cancer (NSCLC) without oncogenic driver mutations is considered to have a poor prognosis, although recent therapeutic progress. This study aims to assess the real-life integration of palliative care (PC) and the intensity of end-of-life (EOL) care for this population. MethodsThis was an observational cohort study of decedent patients from metastatic NSCLC without oncogenic driver mutations over the period 01/2018 to 12/2022, treated in first line with immunotherapy +/- chemotherapy. We analysed PC integration and aggressiveness criteria of EOL care in the last month before death: systemic anti-cancer treatment administration, emergency room visits, intensive care unit admission, hospitalization, hospitalization duration > 14 days, and hospital death. ResultsAmong 149 patients, 75 (50 %) met the PC team at least once, and the median time from the first encounter to death was 2.3 months. In the last month before death, at least one criterion of aggressive EOL care was present for 97 patients (70 %).For patients with PC use < 30 days and for patients with PC use < 90 days before death, there were significant changes: increase in the frequency of systemic anti-cancer treatment (respectively 51.1 % vs 20 %; p < 0.001 and 58.7 % vs 6.2 %; p < 0.001); decrease in hospitalization lasting > 14 days (respectively 30 % vs 7 %; p = 0.001 and 36 % vs 6.2 %; p = 0.018) and in death hospitalisation (respectively 66 % and 18 %; p < 0.001 and 58.7 % and 10.3 %; p < 0.001).After adjusting for the factors tested, patients with no PC or late PC use in the last month before death or in the last three month before death, the odds ratio (OR) remained significantly greater than 1 (respectively OR = 3.97 [1.70; 9.98]; p = 0.001 and OR = 23.1 [5.21–177.0], p < 0.0001). ConclusionPC is still insufficiently integrated for patients with NSCL cancer. Cancer centres should monitor key indicators such as PC use and aggressiveness criteria of EOL care.

Early prehabilitation reduces admissions and time in hospital in patients with newly diagnosed lung cancer.

Lung cancer is the leading cause of cancer death in the UK. Prehabilitation aims to maximise patient fitness and minimise the negative impact of anticancer treatment. What constitutes prehabilitation before non-surgical anticancer treatment is not well established. We present data from a pilot project of Early prehabilitation In lung Cancer. All new patients with likely advanced lung cancer were offered prehabilitation at respiratory clinic, if fit for further investigation. Prehabilitation included assessment and appropriate intervention from a consultant in palliative medicine, registered dietitian and rehabilitation physiotherapist. Four objective endpoints were identified, namely admissions to hospital, time spent in the hospital, treatment rates and overall survival. Outcomes were to be compared with 178 prehab eligible historical controls diagnosed from 2019 to 2021. From July 2021 to June 2023, 65 patients underwent prehabilitation and 72% of patients underwent all 3 interventions. 54 patients had a stage 3 or 4 lung cancer. In the prehab group, fewer patients attended Accident and Emergency (31.5 vs 37.4 attendances per 100 patients) and fewer were admitted (51.9 vs 67.9) when compared with historical controls. Those receiving prehab spent a lot less time in the hospital (129.7 vs 543.5 days per 100 patients) with shorter admissions (2.5 vs 8 days). Systemic anticancer treatment rates increased in the short term but were broadly similar overall. Median survival was higher in the prehabilitation group (0.73 vs 0.41 years, p=0.046). Early prehabilitation appears to reduce time spent in the hospital. It may improve survival. Further work is required to understand its full effect on treatment rates.

Advances in Radionuclide Therapies for Patients with Neuro-endocrine Tumors.

To provide insights into the role of peptide receptor radionuclide therapy (PRRT) in patients with advanced neuroendocrine tumors (NET) and an overview of possible strategies to combine PRRT with locoregional and systemic anticancer treatments. Research on combining PRRT with other treatments encompasses a wide variety or treatments, both local (transarterial radioembolization) and systemic therapies, chemotherapy (i.e., capecitabine and temozolomide), targeted therapies (i.e., olaparib, everolimus, and sunitinib), and immunotherapies (e.g., nivolumab and pembrolizumab). Furthermore, PRRT shows promising first results as a treatment prior to surgery. There is great demand to enhance the efficacy of PRRT through combination with other anticancer treatments. While research in this area is currently limited, the field is rapidly evolving with numerous ongoing clinical trials aiming to address this need and explore novel therapeutic combinations.

Reducing renal function assessment prior to platinum-based chemotherapy: a real-world evaluation.

Platinum-based chemotherapy, a widely used backbone of systemic cytotoxic anticancer treatment, is associated with nephrotoxicity. Currently, renal function is generally assessed prior to each administration of cisplatin or carboplatin, but there is no guideline regarding the frequency of renal function determination. The primary objective was to determine the median time to a clinically relevant dosage adjustment (>10%) due to change in renal function in patients treated with cisplatin and carboplatin. Secondly, variables influencing changes in renal function were assessed. We conducted a retrospective analysis of serial renal function assessments in platinum-treated patients with cancer in two academic medical centers, using a query to extract data from the electronic health records between 2017 and 2019. In total, 512 patients receiving cisplatin and 628 patients receiving carboplatin were included. In total, 15% of all cisplatin-treated patients were found to have a renal function less than 60 mL/min at least once during treatment, with a median time to renal function decline of 67 days (range 5-96 days), which did not differ between treatment regimens. For carboplatin 21% of patients were found to have had a dosage variation of more than 10% at least once during treatment, with a median time-to-event period of 64 days (range 5-100 days). Dose adjustments during platinum-based chemotherapy resulting from renal function decline occur after a median time of ≥64 days. Our data provide substantiated guidance to recommend renal function assessment during platinum-based chemotherapy in clinically stable patients to once every 3 weeks.

Utility of 30-Day Mortality Following Systemic Anti-Cancer Treatment as a Quality Indicator in Advanced Lung Cancer

Background30-day mortality after systemic anti-cancer therapy (SACT) has been suggested as a quality indicator primarily for measuring use of chemotherapy towards the end of life. Utility across different cancer types is unclear, especially when using immunotherapy and targeted therapies. MethodsThis retrospective study included patients with a diagnosis of lung cancer who received palliative-intent SACT at an Australian metropolitan cancer center between 2015 and 2022. Using a prospectively maintained lung cancer database, patient, disease, and treatment characteristics were evaluated against annual 30-day mortality rates following SACT. Results1072 patients were identified. Annual 30-day mortality rate after palliative-intent SACT for lung cancer ranged between 9% and 15%, with significant variance between treatment types. Calculated rates of 30-day mortality are higher if longer reporting time periods are used. Patients who died within 30 days of SACT were more likely to have received targeted therapies or immunotherapy as their final line of treatment, have a poorer performance status at diagnosis, and have received multiple lines of treatment. ConclusionsOur data support differential interpretation of 30-day mortality for quality assurance, especially with regard to lung cancer. Consistency in population and reporting time periods, and accounting for treatment type is crucial if 30-day mortality is to be utilized as cancer care performance quality indicator. Relevance to quality care is questionable in the lung cancer setting.

British Oncology Pharmacy Association Delphi consensus guidelines: Co-infusion of trometamol-containing calcium folinate (Leucovorin) with systemic anti-cancer treatments.

Drug stability and compatibility are critical factors influencing the cost and logistics of treatment delivery, therapeutic effectiveness, and patient safety. This is particularly significant in the realm of cancer chemotherapeutics, where stability and compatibility studies play a vital role in ensuring rational and safe medicine administration. Oxaliplatin, fluorouracil, and irinotecan, commonly used in various combinations for gastrointestinal cancers, are complemented by co-administration of folinic acid in certain protocols. Notably, some folinic acid preparations include trometamol as an excipient, potentially impacting the stability of the chemotherapeutic agents if infused concomitantly. This study seeks to establish guidelines for oncology multidisciplinary teams, addressing potential risks associated with the combination of trometamol-containing folinic acid and chemotherapeutics. To achieve this, a quantitative questionnaire was distributed to members of the British Oncology Pharmacy Association (BOPA) and non-BOPA members through an online survey. Nineteen healthcare professionals with oncology experience, comprising 18 pharmacists and one nurse, completed the questionnaires. Each participant rated the validity and clarity of statements on a 5-point scale. The Delphi process concluded after the fourth round, consolidating the findings and recommendations from the multidisciplinary team. Twelve recommendations for safe practice have been made.

Abstract CT168: A phase 1/2a, multicenter, open-label, non-randomized first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1310 (a HER3-targeting ADC) in patients with advanced/metastatic solid tumors

Abstract Background: Overexpression of epidermal growth factor receptor 3 (HER3 or ERBB3) has been reported in various cancers, including lung, prostate, head and neck, breast, and ovarian cancers, and is associated with disease progression and poor prognosis. DB-1310 is an antibody-drug conjugate (ADC) comprised of a humanized anti-HER3 IgG1 monoclonal antibody, covalently linked to a proprietary DNA topoisomerase I inhibitor (P1021) via a maleimide tetrapeptide-based cleavable linker, with a high drug-to-antibody ratio (~8). Preclinical studies of DB-1310 demonstrated promising antitumor activity in solid tumors and a tolerable safety profile, warranting further clinical development. Methods: This global, first-in-human, Phase 1/2a study includes dose escalation and expansion parts to assess the safety, tolerability, pharmacokinetics, and antitumor activity of DB-1310 in patients (pts) with pretreated advanced/metastatic solid tumors (NCT05785741). Eligible pts must have progressed on or after standard systemic anticancer treatments have ECOG PS ≤1, and evidence adequate organ function. Phase 1 part will evaluate 5 ascending dose levels of DB-1310 with a standard “3+3” design to identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) in pts with advanced/metastatic solid tumors. Phase 2a part will initiate after MTD and/or RP2D are determined and enroll pts with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutation, NSCLC without EGFR activating mutation, castration-resistant prostate cancer, head and neck squamous cell carcinoma, and HER2-positive (immunohistochemistry [IHC] 3+, or IHC 2+ and in situ hybridization-positive) breast cancer (BC). DB-1310 is administrated intravenously every 3 weeks as monotherapy, or plus trastuzumab in pts with HER2-positive BC only, until discontinuation criteria are met. The study plans to enroll approximately 95 pts in Phase 1 and 192 in Phase 2a from the United States and China. Citation Format: Aaron Lisberg, Shun Lu, Alexander Starodub, Harshad Amin, Julia Rotow, Lin Wu, Alexander Spira, Erika Hamilton, Weidi Shen, Liming Liu, Zhongyuan Zhu, Wei Gu, Yang Qiu, Rong Shi, Shengxue Liu. A phase 1/2a, multicenter, open-label, non-randomized first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1310 (a HER3-targeting ADC) in patients with advanced/metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT168.

One million question: How would you reduce admission rate for toxicity from Systemic Anti-Cancer Treatment (SACT) to negligible levels?

One million question: How would you reduce admission rate for toxicity from Systemic Anti-Cancer Treatment (SACT) to negligible levels?

Abstract 927: Real-world (RW) biomarker characteristics and clinical outcomes in pre-treated non-MSI-H/dMMR metastatic colorectal cancer (mCRC) patients

Abstract Introduction: Given sparse RW evidence, we assessed biomarker characteristics &amp; clinical outcomes in community oncology practices among pre-treated non-MSI-H/dMMR mCRC patients. Methods: This retrospective cohort study used structured &amp; chart review data from iKnowMed, The US Oncology Network electronic health record data &amp; included non-MSI-H/dMMR adult mCRC patients pre-treated with standard of care (SoC) chemo who initiated subsequent systemic anticancer treatment (SACT), best supportive care (BSC) or neither from 1/1/2016 - 12/31/2021. Index date for SACT users was the regimen start date post SoC chemo &amp; for patients on BSC &amp; no SACT/BSC, it was last chemo administration date. Patients were followed from index date until 8/31/2022 for overall survival (OS) &amp; real-world progression-free survival (rwPFS). KM analyses assessed outcomes, overall &amp; stratified by treatment, RAS status &amp; metastasis sites. Results: Of mCRC patients with &amp;gt;2 visits, 70.9% received MSI/MMR testing. In 292 eligible chart review patients, 69.5% received SACT in pre-treated setting (regorafenib 14.8%, trifluridine/tipiracil (TAS-102) 12.3%, other 72.9%), 28.8% received BSC &amp; 1.7% neither. 76.7% reported KRAS/NRAS testing with 60.7% wild-type &amp; 39.3% mutant. Common metastasis sites were liver-only (44.2%), liver &amp; lung (10.3%) &amp; lung-only (8.9%). Median (range) duration of follow-up was 5.2 (2.7, 10.0) months for regorafenib, 5.3 (2.5, 8.6) for TAS-102 &amp; 10.7 (5.3, 18.0) for the other treatments group. Median OS was 7.4 (95% CI: 5.8, 8.8) months &amp; median rwPFS was 3.5 (95% CI: 3.2, 4.3) months (outcomes data in Table). Conclusions: 29.1% pre-treated, mCRC patients did not receive guideline recommended MSI/MMR testing, highlighting the need to improve testing. Outcomes varied by treatment, RAS status, &amp; metastatic sites. The modest RW clinical benefit for SoC regorafenib &amp; TAS-102, was consistent with trials &amp; other RW studies; all highlighting an unmet need. Cohorts Median (95% CI) OS (months) Median (95% CI) rwPFS1 (months) Overall 7.4 (5.8, 8.8) 3.5 (3.2, 4.3) Regorafenib 5.6 (3.1, 9.7) 2.4 (1.8, 3.0) TAS-102 5.9 (3.4, 8.6) 3.0 (2.1, 3.4) Other SACT2 12.8 (9.8, 17.2) 4.9 (3.7, 5.8) BSC 2.4 (1.8, 3.2) - RAS mutation Wild-type 8.6 (6.6, 11.5) 4.0 (3.3, 4.9) Mutant 5.4 (3.4, 9.5) 3.2 (2.1, 4.6) Metastatic sites Liver only 8.0 (5.7, 11.7) 3.9 (3.0, 4.9) Lung only 17.0 (7.8, 35.6) 7.9 (3.3, 10.5) Liver &amp; lung only 5.4 (2.4, 7.2) 3.5 (2.1, 5.4) Other 6.7 (4.1, 9.4) 3.2 (2.7, 3.9) Abbreviation: CI: confidence interval, TAS-102: trifluridine/tipiracil, OS: overall survival, rwPFS: real-world progression-free survival, SACT: systemic anticancer treatment 1Overall rwPFS was calculated among patients receiving subsequent SACT only (n = 203) 2Top 2 “other SACT” included irinotecan- or oxaliplatin-based treatment Citation Format: Mayur M. Amonkar, Sneha Sura, Kaushal Desai, Rishi Jain, Zhimei Liu, Nicole Niehoff, Thomas W. Wilson, Gregory Patton, David Cosgrove. Real-world (RW) biomarker characteristics and clinical outcomes in pre-treated non-MSI-H/dMMR metastatic colorectal cancer (mCRC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 927.

Assessing the clinical benefit of systemic anti-cancer treatments in the Netherlands: The impact of different thresholds for effectiveness

BackgroundIn the Netherlands, the clinical benefit of systemic anti-cancer treatments (SACTs) is assessed by the Committee for the Evaluation of Oncological Agents (cieBOM). For non-curative SACTs, the assessment is based on the hazard ratio (HR) for progression-free survival and/or overall survival (OS), and the difference in median survival. We evaluated the impact of different thresholds for effectiveness by reassessing the clinical benefit of SACTs. MethodsWe reassessed SACTs that were initially assessed by cieBOM between 2015 and 2017. Four scenarios were formulated: replacing an “OR” approach (initial assessment) by an “AND” approach (used in all scenarios), changing the HR threshold from < 0.70 (initial assessment) to < 0.60, changing the threshold for the difference in median survival from > 12 weeks (initial assessment) to > 16 weeks, and including thresholds for OS rates. The outcomes of these scenarios were compared to the outcomes of the initial assessment. ResultsReassessments were conducted for 41 treatments. Replacing the “OR” approach by an “AND” approach substantially decreased the number of positive assessments (from 33 to 22), predominantly affecting immunotherapies. This number further decreased (to 21 and 19, respectively) in case more restrictive thresholds for the HR and difference in median survival were used. Including thresholds for OS rates slightly mitigated the impact of applying an “AND” approach. ConclusionsThe scenario-specific thresholds had a substantial impact; the number of negative assessments more than doubled. Since this was not limited to treatments with marginal survival benefits, understanding the potential challenges that may arise from applying more restrictive thresholds is essential.

Case Report on a Multidisciplinary Approach to Address Malnutrition and Improve a Patient’s Fitness for Treatment

Approximately 5,700 people are diagnosed with myeloma each year in the UK. The standard of care is to receive an autologous stem cell transplant after completion of induction therapy. There are no specific dietary recommendations for people with myeloma, however they are at risk of malnutrition due to symptoms and side effects of treatments. This report describes the journey of a 73-year-old male diagnosed with immunoglobulin A (IgA) lambda myeloma in April 2021. The patient lost 23% of his body weight during 6 months of systemic anti-cancer treatment (SACT), resulting in postponing his transplant twice due to reduced fitness. This report describes an effective, although late, multidisciplinary intervention which was successful for the patient who managed to reestablish a healthy weight and good quality of life. The patient received his transplant in January 2023. This case highlights two important aspects of patient care that should not be underestimated in dietetic clinical practice: early screening and multidisciplinary collaboration. Monitoring the nutritional status of patients and providing early nutrition support can prevent hospital admissions, treatment delays and reduce the associated costs. Multidisciplinary teamwork can improve patient care and clinical outcomes, and it is fundamental to strengthen communication and collaboration among clinical disciplines.

Belzutifan for von Hippel-Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study.

Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas]. Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor >3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily. End points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and linear growth rate (LGR) in all pancreatic lesions and pNETs per RECIST version 1.1 by independent review committee, and safety. All 61 enrolled patients (100%) had ≥1 pancreatic lesion and 22 (36%) had ≥1 pNET measurable at baseline. Median follow-up was 37.8 months (range, 36.1-46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs. Median DOR and median PFS were not reached in pancreatic lesions or pNETs. After starting treatment, median LGR for pNETs was -4.2 mm per year (range, -7.9 to -0.8). Eleven patients (18%) had ≥1 grade 3 treatment-related adverse event (AE). No grade 4 or 5 treatment-related AEs occurred. Belzutifan continued to show robust activity and manageable safety in VHL disease-associated pNETs.

Real-world sequential treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in Japan.

Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.