Shafique, Nouman

e20097 Background: Malignant Mesothelioma (MMe) is a neoplasm of mesothelium and has a very poor survival rate. Over half the patients of MMe express programmed death-ligand 1 (PD-L1) which binds to the PD-1 receptor on T-cells which in turn suppresses their ability to kill tumors. Pembrolizumab is a PD-1 inhibitor antibody and it has shown efficacy in combating MMe. Our analysis aims to summarize data related to objective response rates (ORR) and adverse effects of Pembrolizumab therapy in MMe patients. Methods: We conducted an online search through PubMed, Cochrane, and Clinicaltrials.gov databases from their inception till January 25, 2024, to identify studies that reported the use of Pembrolizumab in patients with MMe. Data were extracted and analyzed and proportions with their 95% confidence interval have been reported. Onlinemeta v1.0 was used for all analyses. Results: A total of six studies with 549 patients reported the use of Pembrolizumab in patients with MMe. ORR was observed in 36.2% (32.3% - 40.4%; p < 0.01) of patients receiving Pembrolizumab while 20.4% (17.2%- 24.0%; p < 0.01) of patients experienced adverse effects of the therapy. Median survival ranged from 9.5 to 17.3 months whereas progression-free survival ranged from 2.5 to 7.1 months in patients. Conclusions: Pembrolizumab has an ORR and safety profile comparable to other immunotherapies. Further studies are needed to extensively study the drug and its effects in detail in patients with MMe. [Table: see text]

e18073 Background: Selpercatinib is a highly selective RET inhibitor that is used for the treatment of RET-mutant medullary thyroid cancers, but its efficacy and safety is not fully understood. Our objective is to summarize available literature on the safety and efficacy profile of Selpercatinib. Methods: A search was conducted on PubMed, Embase and Cochrane from foundation to 31st January 2024. Patients aged above 18 with Advanced RET-Altered Medullary Thyroid Cancers who received Selpercatinib were identified. Data abstraction was done based on objective response rate, complete response rate, any grade adverse effect (AE) and grade ≥3 AE. Analysis was done using R (v.4.3) and reported as proportions with respective 95% confidence intervals (CI) on forest plots. Results: Four studies were identified that reported the use of Selpercatinib in Advanced RET-Altered Medullary Thyroid Cancers. Our analysis showed that the pooled proportion of objective response rate and complete response rate was 74.8% (95% CI: 70.1% – 79%) and 4.9% (95% CI: 3.1% – 7.7%) respectively. Pooled proportion of patients experiencing any grade AE and grade ≥3 AE was 93.4% (95% CI: 90.4% – 95.6%) and 46.2% (95% CI: 41.1% – 51.3%) respectively. Conclusions: Selpercatinib is a novel RET inhibitor which has potential use against RET-Altered Thyroid Cancers. It has an overall acceptable safety and efficacy profile. However it requires further studies to establish its adverse effects and clinical application. [Table: see text]

e16531 Background: Hypoxia-inducible Factor-2α (HIF-2α) is a transcription factor that accumulates in clear cell renal cell carcinoma (ccRCC) and is responsible for genes involved in oncogenesis. Belzutifan is a HIF-2α inhibitor that has shown promising anti-tumor effects in patients with ccRCC. Our objective is to summarize the available literature on the safety and efficacy profile of the drug. Methods: An electronic search was conducted on PubMed, Embase, and Cochrane from inception till January 31st, 2024. We identified patients aged ≥ 18 years with ccRCC who received Belzutifan. We extracted data on objective response rate, complete response rate, any grade adverse effect (AE) and grade ≥3 AE. Data was analyzed using R (v.4.3) and reported as proportions with respective 95% confidence intervals (CI) on forest plots. Results: Three studies (n=168 patients) were identified that reported the use of Belzutifan in ccRCC. Our analysis showed that pooled proportion of objective response rate and complete response rate was 35% (95% CI: 24% – 47%) and 1% (95% CI: 0% – 5%) respectively. Pooled proportion of patients experiencing any grade AE and grade ≥3 AE was 98% (95% CI: 95% – 99%) and 49% (95% CI: 29% – 69%) respectively. Conclusions: Belzutifan is a novel drug that inhibits HIF-2α which in turn results in anti-tumor effects of the drug against ccRCC. The drug has an acceptable safety and efficacy profile from limited data but more studies are needed to establish a complete picture of drug’s adverse effects and clinical benefits. Pooled proportion of patients developing (A) Objective Response, (B) Complete response (C) Any adverse effect and (D) Grade ≥3 adverse effects. [Table: see text]

e24003 Background: Cancer patients undergoing chemotherapy suffer from a variable degree of cancer therapy–related cardiac dysfunction and heart failure (HF). It is known that sodium glucose co-transporter 2 (SGLT2) inhibitors improve outcomes in patients with HF independent of diabetes mellitus and left ventricular ejection fraction; our study aims to investigate the potential benefits of SGLT2 inhibitory therapy specifically in cancer patients undergoing chemotherapy. Methods: We performed an electronic search on PubMed, Embase, and Cochrane, from the inception of databases till January 29, 2024, to identify all the articles that compared the use of SGLT2 inhibitors in adult (≥18 years) with type 2 diabetes mellitus and exposure to cardiotoxic antineoplastic therapy, subsequently diagnosed with cardiomyopathy, heart failure, or LVEF < 40%. The data was extracted and pooled using a random effects model to calculate the odds ratio (OR) with a respective 95% confidence interval (CI). R software (v.4.3) was used for all statistical analyses. Results: Our search identified three observational studies with a total of 3,164 patients (SGLT2- inhibitor group: 1,550; Control group: 1,614). We found that the use of SGLT2 inhibitors was associated with a lower risk of all-cause mortality (OR: 0.25 [0.20, 0.31]; I2 = 16%; p < 0.001), hospitalizations from heart failure (OR: 0.25 [0.10, 0.62]; I2 = 0%; p = 0.003), and acute exacerbation of heart failure (OR: 0.35 [0.27, 0.47]; I2 = 0%; p < 0.001). Conclusions: Our findings suggest a favorable association between the use of SGLT2 inhibitors and reduced mortality, as well as improved cardiac clinical outcomes in cancer patients undergoing chemotherapy. However, further validation through large-scale studies and randomized controlled trials across diverse malignancies is warranted to establish the efficacy of these drugs. [Table: see text]

Introduction: The safety and efficacy of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) remain unknown in patients with BMI ≥ 40 kg/m 2 . We aim to evaluate the risk of recurrent VTE and major bleeding in patients with a BMI ≥ 40 when started on DOACs versus VKAs. Methods: We conducted a systematic literature search according to PRISMA guidelines to identify studies using the terms: “venous thromboembolism”, “Vitamin K antagonists” and “direct oral anticoagulants”. After the screening, We extracted the data till May 2023 in a data extraction sheet. Our inclusion criteria were: adult patients, morbidly obese (BMI ≥ 40 kg/m 2 ), who were on DOACs or VKAs for VTE or atrial fibrillation. We used a variance-weighted random-effects model to analyze data on DOACs vs. VKAs, estimating event rates and odds ratios while assessing heterogeneity. Data were analyzed using the ‘meta’ package in R. Results: Our analysis included a total of 16 studies (n= 62704 patients). Obese patients on DOACs had a significant reduction in the risk of recurrent VTEs compared to VKAs OR 0.72 (95% CI: 0.59 - 0.88, I2 :19%). Also, DOACs were associated with a lower risk of major bleeding compared to VKAs in morbidly obese patients (OR = 0.65, 95% CI: 0.58 - 0.74, I2 :0%). For non-major bleeding, although the statistical significance was not reached, a consistent trend favoring DOACs was observed (OR = 0.76, 95% CI: 0.47-1.21). (Figure1) Conclusions: Among morbidly obese patients (BMI ≥ 40), DOACs are associated with a significantly lower risk of recurrent VTEs, and major bleeding compared to VKA. For non-major bleeding, there was a trend favoring DOACs over VKA. Increased recruitment of obese patients in clinical trials is needed to provide us with robust data for informed clinical decision-making.