Systemic Therapy Research Articles

390. CONTINUED IMPLICATIONS OF THE COVID-19 PANDEMIC ENVIRONMENT ON ESOPHAGEAL CANCER CHARACTERISTICS AND TREATMENT IN THE UNITED STATES

Abstract Background The COVID-19 pandemic significantly impacted the stage of presentation and subsequent therapies for patients who were diagnosed with esophageal cancer during the first pandemic year. We aimed to assess for continued implications of the altered healthcare landscape on esophageal cancer presentation and treatment in the second year of the pandemic. Methods This was a retrospective review of the United States National Cancer Database (2019-2021). Demographic, cancer-related and treatment variables were compared between patients diagnosed in the pre-pandemic year (2019), pandemic year one (2020) and pandemic year two (2021). Multivariate logistic regression was performed to control for the impact of demographics on oncologic variables, and then for the impact of oncologic variables on treatment modalities and outcomes. Results Of 42,807 esophageal cancer cases, 15,127 (35.3%) were pre-pandemic, 13,975 (32.7%) were pandemic year 1, and 13,705 (32.0%) were pandemic year two. There were significant differences in the distribution of clinical stage at presentation by year (p=0.0001), see figure, suggesting more advanced stage presentation throughout the pandemic. Compared to the pre-pandemic year, patients diagnosed in pandemic year two had risk-adjusted increases in time to first course treatment (incidence rate ratio 1.057 [95% confidence interval [1.036–1.078]), to radiation (1.029 [1.008–1.050]), and to systemic therapy (1.035 [1.018–1.051]). Additionally, when compared to pandemic year one, patients in pandemic year two continued to experience risk-adjusted increases in time to first course therapy (1.084 [1.063–1.106]), to surgery (1.049 [1.000–1.097]), to radiation (1.046 [1.024–1.068]) and to systemic therapy (1.060 [1.043–1.077]). Conclusions Compared to the pre-pandemic year, patients diagnosed with esophageal cancer in in the U.S. during pandemic year two continued to experience delays to treatment including delays to first course therapy, including delays to surgery, radiation and systemic therapy. The treatment characteristics of esophageal cancer have not returned to pre-pandemic baseline in the United States possibly due to compounding delays to diagnosis and treatment and a growing back log of cases.

50377 Factors associated with the initiation of a new systemic therapy among adults with atopic dermatitis: Data from the CorEvitas Atopic Dermatitis Registry

50377 Factors associated with the initiation of a new systemic therapy among adults with atopic dermatitis: Data from the CorEvitas Atopic Dermatitis Registry

591P Cost-utility of systemic anticancer therapy (SACT) with or without metastasectomy including local ablative therapy (LAT) for metastatic colorectal cancer (mCRC) patients

591P Cost-utility of systemic anticancer therapy (SACT) with or without metastasectomy including local ablative therapy (LAT) for metastatic colorectal cancer (mCRC) patients

A Comprehensive Review of Systemic Targeted Therapies in Cancer Treatment

Abstract: Cancer is one of the significant healthcare challenges in today’s world, even after advancements in modern science, including oncology. The complex nature of the disease, which involves multiple proteins and pathways, poses a substantial challenge in drug discovery. Several therapeutic options have emerged in the last decade. Systemic cancer therapies began with the advent of chemotherapy and were revolutionized with the development of targeted therapies. The present review is a definite overview of the advances in various therapeutic options for cancer, with a particular emphasis on targeted therapy using small molecules and biologicals.

Savolitinib in patients in China with locally advanced or metastatic treatment-naive non-small-cell lung cancer harbouring MET exon 14 skipping mutations: results from a single-arm, multicohort, multicentre, open-label, phase 3b confirmatory study.

Savolitinib has been approved in China for advanced or metastatic non-small-cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations in previously treated patients and those unable to receive platinum-based chemotherapy. We report results from a treatment-naive cohort of a phase 3b study that was designed to evaluate the efficacy and safety of savolitinib in locally advanced or metastatic METex14-mutated NSCLC. This single-arm, multicohort, multicentre, open-label, phase 3b study was done at 48 hospitals in China in adult (≥18 years) patients with locally advanced or metastatic METex14-mutated NSCLC who had not received previous systemic antitumour therapy. Patients with a bodyweight of 50 kg or more and those with a bodyweight of less than 50 kg received savolitinib once daily at 600 mg or 400 mg, respectively, in 21-day cycles. The primary endpoint was objective response rate assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumours, version 1.1. The full analysis set comprised all patients who received at least one dose of study medication, which was used to assess the efficacy endpoints and baseline and safety data. This study is registered with ClinicalTrials.gov (NCT04923945) and is closed to accrual. Between Aug 31, 2021, and Oct 20, 2023, 125 treatment-naive patients were assessed for eligibility, of whom 87 were enrolled and received savolitinib. The median age of patients was 70·0 years (IQR 65·2-75·8) and 51 (59%) of 87 patients were male and 36 (41%) were female. In the full analysis set, the IRC-assessed objective response rate was 62% (95% CI 51-72) and the investigator-assessed objective response rate was 60% (49-70), showing a high concordance rate (84%). Treatment-related adverse events were reported in 85 (98%) of 87 patients, with peripheral oedema (54 [62%]) being the most common. Two of these treatment-related adverse events led to death (cardiac failure n=1, unknown reasons n=1). Savolitinib showed manageable toxicity and promising efficacy in treatment-naive patients with advanced or metastatic METex14-mutated NSCLC. HUTCHMED and AstraZeneca.

Safe and supportive prescribing in transgender and non-binary patients with cancer.

Global prevalence rates for transgender individuals vary with estimates ranging from 0.3% to 1%, translating to a potential global population of 24.3 million to 81 million. It is estimated that one in two people will develop cancer in their lifetime. Gender-affirming hormone therapy (GAHT) is a common medical intervention for transgender and non-binary individuals. GAHT requires careful consideration for concurrent medical care due to potential drug interactions and physiological changes. A multi-disciplinary team with expertise in transgender health, oncology and pharmacy met to develop a document summarizing current knowledge on the topic for practical use. The team included trans and non-binary authors who shaped the document's language and focus. The document gives a status update on the current understanding of GAHT and how this may intersect with the safe prescribing of systemic anti-cancer therapies (SACT). The document underwent multiple review stages including internal review, review by the British Oncology Pharmacy Association (BOPA) EDI Subcommittee and, finally, BOPA Executive Committee review and final approval. Key recommendations of this document include the use of inclusive and effective communication, vigilant monitoring of kidney function and cardiovascular health, and considerations for hormone receptor-positive cancers. The document also recognizes the multidisciplinary nature of transgender healthcare and where this relates to social prescribing.

286. TREATMENT WITH CURATIVE INTENT FOR OLIGOMETASTATIC GASTROESOPHAGEAL CANCER-RESULTS OF A PROSPECTIVE MULTICENTER STUDY

Abstract Background Oligometastatic gastroesophageal cancer is a clinical entity with no standard treatment recommendation. Treatment with curative intent has recently emerged as an option in selected patients in contrast to the traditional palliative treatment strategy. This prospective study aimed to assess the safety and efficacy of combined systemic and local treatment with curative intent for patients with oligometastatic gastroesophageal cancer. Methods In a multicenter collaborative study, consecutive patients with gastroesophageal cancer and metastases in the liver and/or extra-regional lymph nodes were screened for inclusion. Eligible patients were offered treatment with combined systemic and local therapy within the study. Primary endpoints were treatment safety and feasibility, secondary outcomes included postoperative mortality, treatment response, progression-free and overall survival. Subgroup analyses were stratified based on oligometastatic location. Results A total of 29/35 patients completed systemic and local treatment with surgical resection, liver ablation or definitive chemoradiotherapy. The majority of postoperative complications were mild-moderate, no patient died due to postoperative complications within 30 days of surgery. Median progression-free survival was 7.1 (interquartile range 4.3-12.4) months and median overall survival was 23.8 (interquartile range 12.3-33.0) months. Conclusion This study found combined systemic and local treatment to be a safe treatment option and to potentially improve long-term survival in strictly selected patients with oligometastatic gastroesophageal cancer.

1168P Overall survival (OS) and progression-free survival (PFS) in patients with advanced, non-resectable, progressive rectal NET treated with 90Y DOTA-TATE, 177Lu DOTA-TATE and mix of both as systemic radioligand therapy: Real-world data

1168P Overall survival (OS) and progression-free survival (PFS) in patients with advanced, non-resectable, progressive rectal NET treated with 90Y DOTA-TATE, 177Lu DOTA-TATE and mix of both as systemic radioligand therapy: Real-world data

1798P Relapsed and refractory systemic therapy real-world outcomes in the Canadian small cell lung cancer database (CASCADE)

1798P Relapsed and refractory systemic therapy real-world outcomes in the Canadian small cell lung cancer database (CASCADE)

Contemporary Molecular Markers for Predicting Systemic Treatment Response in Urothelial Bladder Cancer: A Narrative Review.

The search for dependable molecular biomarkers to enhance routine clinical practice is a compelling challenge across all oncology fields. Urothelial bladder carcinoma, known for its significant heterogeneity, presents difficulties in predicting responses to systemic therapies and outcomes post-radical cystectomy. Recent advancements in molecular cancer biology offer promising avenues to understand the disease's biology and identify emerging predictive biomarkers. Stratifying patients based on their recurrence risk post-curative treatment or predicting the efficacy of conventional and targeted therapies could catalyze personalized treatment selection and disease surveillance. Despite progress, reliable molecular biomarkers to forecast responses to systemic agents, in neoadjuvant, adjuvant, or palliative treatment settings, are still lacking, underscoring an urgent unmet need. This review aims to delve into the utilization of current and emerging molecular signatures across various stages of urothelial bladder carcinoma to predict responses to systemic therapy.

Survival prognostic factors in nonsmall cell lung cancer patients with simultaneous brain metastases and poor performance status at initial presentation

PurposeAlthough the treatment of nonsmall cell lung cancer (NSCLC) has rapidly progressed recently, there is little evidence of treatment for patients with symptomatic brain metastases (BM) and poor performance status (PS). However, in symptomatic BM patients, appropriate upfront intracranial treatment can often lead to rapid improvement in PS and effective systemic therapy. Thus, this study investigated the prognostic factors for the survival of poor PS NSCLC patients with synchronous BM. MethodsData of patients with BM and Karnofsky PS (KPS) ≤70 at the first diagnosis of NSCLC who were treated in our hospital between January 2017 and December 2021 were reviewed. Patient survival was compared among patients stratified by type of first-line regimen of systemic treatment. Correlations between patient characteristics and survival were examined. ResultsFifty patients receiving aggressive treatment were enrolled. The median survival times for tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor (ICI), and chemotherapy alone groups were 19 (95% confidence interval [CI], 2.8–68.5), 19 (3.0–62.0), and 13 (1.2–24.8) months, respectively. Survival in the TKI and ICI groups was significantly longer than in the chemotherapy alone group (p = 0.046, TKI vs. chemo; p = 0.022, ICI vs. chemo; p = 0.023). Both sex and type of systemic treatment correlated to survival time on univariate analysis. Chemotherapy alone for systemic treatment [p = 0.034; hazard ratio (HR), 0.44 (0.20–0.94)] remained significant for predicting overall survival in the multivariate analysis. ConclusionEven in patients with poor PS and BM at the initial diagnosis of NSCLC, the ICI group had a survival time comparable to that of the TKI group when combined with tailor-made intracranial treatment. There is a subgroup in the patient population that was previously considered unsuitable for ICI, whose PS improves with individualized intracranial treatment, and who may benefit from immunotherapy.

A pH-Responsive Drug-Delivery System Based on Apatinib-Loaded Metal-Organic Frameworks for Ferroptosis-Targeted Synergistic Anti-Tumor Therapy.

The efficacy of systemic therapy for hepatocellular carcinoma (HCC) is limited mainly by the complex tumor defense mechanism and the severe toxic side-effects of drugs. The efficacy of apatinib (Apa), a key liver cancer treatment, is unsatisfactory due to inadequate targeting and is accompanied by notable side-effects. Leveraging nanomaterials to enhance its targeting represents a crucial strategy for improving the effectiveness of liver cancer therapy. A metal polyphenol network-coated apatinib-loaded metal-organic framework-based multifunctional drug-delivery system (MIL-100@Apa@MPN) was prepared by using metal-organic frameworks (MOFs) as carriers. The nanoparticles (NPs) were subsequently characterized using techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), zeta potential measurements, and particle size analysis. In vitro experiments were conducted to observe the drug release kinetics and cytotoxic effects of MIL-100@Apa@MPN on HepG2 cells. The in vivo anti-tumor efficacy of MIL-100@Apa@MPN was evaluated using the H22 tumor-bearing mouse model. The formulated MIL-100@Apa@MPN demonstrates remarkable thermal stability and possesses a uniform structure, with measured drug-loading (DL) and encapsulation efficiency (EE) rates of 28.33% and 85.01%, respectively. In vitro studies demonstrated that HepG2 cells efficiently uptake coumarin-6-loaded NPs, and a significant increase in cumulative drug release was observed under lower pH conditions (pH 5.0), leading to the release of approximately 73.72% of Apa. In HepG2 cells, MIL-100@Apa@MPN exhibited more significant antiproliferative activity compared to free Apa. In vivo, MIL-100@Apa@MPN significantly inhibited tumor growth, attenuated side-effects, and enhanced therapeutic effects in H22 tumor-bearing mice compared to other groups. We have successfully constructed a MOF delivery system with excellent safety, sustained-release capability, pH-targeting, and improved anti-tumor efficacy, highlighting its potential as a therapeutic approach for the treatment of HCC.

52332 Safety of Total Skin Electron Therapy with Concurrent Systemic Therapy

52332 Safety of Total Skin Electron Therapy with Concurrent Systemic Therapy

555. SUPRACLAVICULAR NODE INVOLVEMENT, A NODAL OR METASTATIC DISEASE? - A 10-YEAR EXPERIENCE IN ESOPHAGEAL CARCINOMA AT A TERTIARY REFERRAL CENTRE

Abstract Background Despite the advance in neoadjuvant chemothepray/chemoradiotherapy and favourable outcomes of surgical management in supraclavicular lymph node (SCLN) involvement reported in recent studies, the latest AJCC/UICC TMN classification still regards SCLN metastasis as extra-regional i.e Stage IVB (M1) disease. The role of SCLN dissection and surgical management remain controversial. At National University Hospital of the present study, bilateral supraclavicular lymphadenectomy is routinely performed for resectable thoracic ESCC. The aim of this retrospective cohort study is to investigate the long-term outcome of surgical management in pathological SCLN metastasis and its survival benefit comparing to Stage IIB-IVA diseases. Methods Patients with ESCC who underwent esophagectomy and 3-field lymphadenectomy with curative intent between January 2013 and January 2023 at the single centre were included; cases of salvage esophagectomy post-definitive concurrent chemoradiotherapy, palliative resections, and concurrent head and neck cancers were excluded. Neoadjuvant treatments were considered in cases staged clinically as T2 and/or N1 or greater. Pathological status of lymph nodes was recorded according to JES classification. Demographics and prognostic factors were examined using univariant analysis of overall survival (OS). Patients with SCLN metastases and other LN involvements were compared and OS were analysed using Kaplan-Meier method. Results 544 patients were included. 183 had one or more pathological LN metastasis (pN1:126, pN2 46, and PN3: 11) in which 55 patients had SCLN metastasis. Patients with LN metastasis had poorer prognosis than those without (pN0) with a Hazard Ratio (HR) of 2.68 (95% CI, 1.12-3.40, p<0.01); similar pattern was seen in patients with SCLN metastasis (HR 2.28, p<0.01). The 3-year and 5-year OS of patients with SCLN metastasis was 18.5% and 11.6% respectively whereas those of other LN metastasis was 21.4% and 15.8%; the difference between the groups was not statistically significant (p=0.525) (graph 1). Conclusion Lymph node status (pN) is a well-recognised prognostic factor as reaffirmed, however, within the pN positive cohort, long-term survival of patients with SCLN metastasis, considered as stage IVB (M1), was comparable (p<0.05) to those with other LN metastases. This supports the survival benefit of surgical resection with neoadjuvant therapy in SCLN metastases as following nodal disease treatment algorithm; further evaluation including systemic therapy and lymph node sub-group analysis is being conducted. Whilst randomised controlled trials such as Japanese JCOG2013 provides level I evidence, the present study provides complementary real-world experience for SCLN dissection.

1460P Association between effectiveness of treatment with curative intent and outcomes of first-line systemic therapy in metachronous metastatic esophagogastric cancer

1460P Association between effectiveness of treatment with curative intent and outcomes of first-line systemic therapy in metachronous metastatic esophagogastric cancer

Rationale and Design of the COPERNIC Trial: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients

BackgroundEvidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies. MethodsCOPERNIC is an international, multicenter clinical trial. The pilot study aims to confirm the predictive potential of early on-treatment ctDNA dynamics, and inform the design of a larger ctDNA-driven trial. Advanced CRC patients who are candidates for ≥3rd lines of systemic therapy undergo longitudinal blood sample collection during treatment (day 1, 15 and 29 for 2- or 4-weekly treatment regimens; day 1, 22 and 43 for 3-weekly treatment regimens) and at each imaging assessment. ctDNA analyses are carried out with the FoundationOne Liquid CDx and FoundationOneMonitor assays, and ctDNA changes during treatment are correlated with radiologic response (as assessed every 8-12 weeks by RECIST v1.1). The primary objective is to select the optimal timepoint and cut-off value for early ctDNA changes (at D15/D22) to predict progressive disease as best radiological response with a high positive predictive value. The cut-off value for ctDNA will be defined based on nonparametric ROC-curves with bootstrapping. Based on the expected rate of progressive disease and statistical assumptions, 109 patients are needed to be screened to have 87 assessable patients. COPERNIC is sponsored by the Institut Jules Bordet, and supported by Roche and Foundation Medicine. Recruitment is open in 13 centres across Belgium and France. The study is registered with clinicaltrials.gov (NCT05487248).

Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma

Belzutifan is a first-in-class HIF-2α inhibitor approved at a dose of 120 mg once daily for certain adults with VHL disease and adults with advanced renal cell carcinoma (RCC) following therapy with a programmed death receptor (or ligand)-1 (PD-[L]1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor. However, whether belzutifan dose could be optimized is unclear. The phase 2 LITESPARK-013 study (NCT04489771) enrolled patients with advanced clear cell RCC whose disease progressed after 1-3 prior systemic therapies, including an anti-PD-(L)1 regimen. Patients were randomly assigned 1:1 to receive belzutifan 120 mg or 200 mg once daily. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Overall, 154 patients were enrolled (120 mg: n = 76; 200 mg: n = 78). Median follow-up was 20.1 months (range 14.8-28.4). ORR was 23.7% vs 23.1% for the 120 mg and 200 mg groups, respectively (P = 0.5312; -0.5% [95% CI, -14.0 to 12.9]. Median DOR was not reached for the 120 mg arm and was 16.1 months (2.1+ to 23.5+) for the 200 mg arm. No between-group differences were observed for PFS (HR 0.94 [95% CI 0.63-1.40]) or OS (medians not reached; HR 1.11 [95% CI, 0.65-1.90]). Grade 3 or 4 treatment-related adverse events were observed in 35 patients (46.1%) in the 120 mg group and 36 patients (46.2%) in the 200 mg group. The efficacy of belzutifan was similar between the 120-mg dose and the 200-mg dose for previously treated clear cell RCC. Safety at both doses was consistent with the known safety profile of belzutifan. These results further support 120 mg once daily as the preferred dose for belzutifan.

2018P Nephron-sparing surgery combined with perioperative systemic therapy in select high-risk upper tract urothelial carcinoma (UTUC) Patients: A pilot study for a prospective phase II trial

2018P Nephron-sparing surgery combined with perioperative systemic therapy in select high-risk upper tract urothelial carcinoma (UTUC) Patients: A pilot study for a prospective phase II trial

1905P Impact of proactive callback in patients with solid tumors receiving systemic therapy: A meta-analysis

1905P Impact of proactive callback in patients with solid tumors receiving systemic therapy: A meta-analysis

430. PROGNOSTIC PATTERNS OF LYMPH NODES WITH COMPLETE TREATMENT RESPONSE IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER NEOADJUVANT CHEMORADIOTHERAPY AND NEOADJUVANT CHEMOTHERAPY

Abstract Background The prognostic significance of lymph nodes with pathological complete treatment response (pcr-LN) has not been well investigated in esophageal squamous cell carcinoma (ESCC). We aimed to determine the prognostic impact of pcr-LNs in ESCC after either neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). Methods 578 patients with ESCC from two medical facilities were analyzed retrospectively, with 303 patients receiving nCRT and 275 receiving nCT. Pcr-LNs were defined as LNs exhibiting regression changes, such as fibrosis, mucin lakes, keratinization, and giant cell responses but no evidence of living tumor cells. 5 LN status subgroups were identified based on the ypN category in 8th AJCC: ypN0/pcr-LN-, ypN0/pcr-LN+, ypN1, ypN2, and ypN3. The Kaplan-Meier approach was used to analyze the overall survival (OS), and subgroup findings were compared using the log-rank test. Multivariate analysis of OS was performed using a Cox proportional hazard model. Results 45 patients were classified into ypN0/pcr-LN+ (7.8%), 33 in the nCRT group, and 12 in the nCT group (p = 0.006). Compared to the nCRT group, the nCT group underwent a more thorough LN dissection (LN (mean (SD)): nCRT, 21.05 (8.77); nCT, 26.08 (11.66); p = 0.001). Survival analysis of OS showed the subgroup ypN0/pcr-LN+ had a significantly worse prognosis than ypN0/pcr-LN- in the nCRT group (p = 0.047), but no difference was seen in the nCT group. Multivariable analysis revealed that ypN0/pcr-LN+ patients in the nCRT group had a greater risk of mortality than ypN0/pcr-LN- patients (p = 0.0487). Conclusion The nCRT group had a more noticeable complete treatment response in LNs than the nCT group. However, in comparison to the nCT group, the nodal downstaging with radiotherapy in the nCRT group may not translate into improved outcomes. More aggressive systemic therapy might be required to improve the overall survival in esophageal cancer patients receiving neoadjuvant treatment.