Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the human epidermal growth factor receptor 2 (HER2)-positive BCBM population. We searched PubMed, Embase, and Cochrane Library databases as well as American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and San Antonio Breast Cancer Symposium (SABCS) websites for clinical trials (CTs) and observational studies evaluating T-DXd in patients with HER2-positive BCBM. Heterogeneity was assessed with I² statistics. Random effects models were used for all statistical analyses, which were carried out using R software (version 4.2.2). Ten studies were included, six CTs (n = 189) and four observational studies (n = 130), with a total of 319 patients. The median progression-free survival was 15 months [95% confidence interval (CI) 13.9-16.1 months]. The objective response rate (ORR) was 61% (95% CI 52% to 70%), and the intracranial (IC)-ORR was 61% (95% CI 54% to 69%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (P = 0.31 and 0.58, respectively). The clinical benefit rate (CBR) was 80% (95% CI 52% to 94%), and the IC-CBR was 70% (95% CI 54% to 82%). The ORR was 68% (95% CI 57% to 77%) in the subgroup of patients with stable BMs and 60% (95% CI 48%-72%) in patients with active BM, with no significant difference between groups (P = 0.35). Our systematic review and meta-analysis supports the IC activity of T-DXd in patients with stable BM and active BM. International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023422589.

Clinical manifestations and severity of SARS-CoV-2 infection in individuals with sickle cell disease (SCD) and sickle cell trait (SCT) are not well understood yet. We performed a systematic review and meta-analysis to assess COVID-19 outcomes in individuals with SCD or SCT compared to individuals without sickle cell disease or trait. An electronic search on PubMed, Embase, and Cochrane Library was performed on August 3, 2023. Two authors (IFM and ISP) independently screened (IFM and ISP) and extracted data (IFM and ILC) from included studies. Main exclusion criterion was the absence of the non-SCD/SCT group. Exposure effects for binary endpoints were compared using pooled odds ratio (OR) with 95% confidence intervals (CI). I² statistics was used to assess the heterogeneity and DerSimonian and Laird random-effects models were applied for all analyses to minimize the impact of differences in methods and outcomes definitions between studies. The overall quality of evidence was assessed using the GRADE system. Review Manager 5.4 and R software (v4.2.2) were used for statistical analyses. Registered with PROSPERO, CRD42022366015. Overall, 22 studies were included, with a total of 1892 individuals with SCD, 8677 individuals with SCT, and 1,653,369 individuals without SCD/SCT. No difference in all-cause mortality was seen between SCD/SCT and non-SCD/SCT (OR 1.18; 95% CI 0.78–1.77; p = 0.429; I² = 82%). When considering only studies adjusted for confounders (8 studies), patients with SCD/SCT were shown to be at increased risk of death (OR 1.86; 95% CI 1.30–2.66; p = 0.0007; I² = 34%). No significant difference was seen between individuals with SCD and SCT (p = 0.863). The adjusted for confounders analysis for hospitalisation revealed higher rates for the SCD (OR 5.44; 95% CI 1.55–19.13; p = 0.008; I² = 97%) and the SCT groups (OR 1.31; 95% CI 1.10–1.55; p = 0.002; I² = 0) compared to the non-SCD/SCT population. Moreover, it was significantly higher for the SCD group (test for subgroup difference; p = 0.028). Our findings suggest that patients with SCD or SCT may present with a higher mortality and hospitalisation rates due to COVID-19 infection. None.

Background: Until recently, targeted therapies have failed to benefit patients with human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC). Nevertheless, antibody–drug conjugates (ADCs) have reshaped their prognosis. Objectives: We performed a systematic review and meta-analysis to assess the effectiveness of ADCs in patients with HER2-low advanced/metastatic (a/m) BC. Design: This study is a systematic review and meta-analysis. Data sources: We searched PubMed, Embase, and Cochrane databases as well as the American Society of Clinical Oncology, European Society for Medical Oncology, and San Antonio Breast Cancer Symposium conference proceedings. Methods: Studies evaluating ADCs (trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), MRG002, and RC48-ADC) in patients with HER2-low a/mBC were included. We used R software (v.4.2.2) and random effects models for all analyses. Heterogeneity was assessed using the I² test. Results: Overall, 14 studies were included (five real-world studies and nine clinical trials (CTs)), with 2883 HER2-low a/mBC patients: 808 received treatment of physician’s choice (TPC), and 2075 ADCs. Most were treated with T-DXd ( n = 1691), followed by SG ( n = 310), MRG002 ( n = 56), and RC48-ADC ( n = 18). Patients treated with T-DXd achieved a significantly higher objective response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) than those receiving other ADCs. In the pooled analysis of four randomized CTs, ADCs statistically prolonged progression-free survival ( n = 1828, hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.36–0.68, I² = 82%, p < 0.001) and overall survival ( n = 1546, HR 0.70, 95% CI 0.57–0.86, I² = 43%, p < 0.001) compared with TPC. Patients on ADCs also achieved a greater antitumor response than TPC, including better ORR (odds ratio (OR), 3.7, 95% CI 2.5–5.6, I² = 59%, p < 0.001), DCR (OR, 2.7, 95% CI 2.1–3.5, I² = 0%, p < 0.001), and CBR (OR, 3.6, 95% CI 2.6–5.2, I² = 56%, p < 0.01). Conclusion: Our systematic review and meta-analysis confirms the efficacy of ADCs in HER2-low a/m BC patients over TPC. Future studies should focus on bringing ADCs into earlier lines of therapy in this population. Trial registration: This study was registered in PROSPERO (CRD42024452962).

Purpose: There is no agreed-upon standard option for patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) unfit for cisplatin-based regimens. Therefore, we performed a systematic review to explore alternative options for this population. Methods: We searched PubMed, Cochrane, and Embase databases for observational studies and clinical trials (CTs) assessing treatment options for LA HNSCC cisplatin-ineligible patients. This study was registered in PROSPERO under the number CRD42023483156. Results: This systematic review included 24 studies (18 observational studies and 6 CTs), comprising 4450 LA HNSCC cisplatin-ineligible patients. Most patients were treated with cetuximab-radiotherapy [RT] (50.3%), followed by carboplatin-RT (31.7%). In seven studies reporting median overall survival (OS) in patients treated with cetuximab-RT, it ranged from 12.8 to 46 months. The median OS was superior to 40 months in two studies assessing carboplatin-RT, and superior to 15 months in two studies assessing RT alone. For other regimens such as nimotuzumab-RT, docetaxel-RT, and carboplatin-RT plus paclitaxel the median OS was 21, 25.5, and 28 months, respectively. Conclusions: Our systematic review supports the use of a variety of therapy combinations for LA HNSCC cisplatin-ineligible patients. We highlight the urgent need for clinical studies assessing treatment approaches in this population.

We performed a systematic review and meta-analysis to assess the efficacy of EGFR-tyrosine kinase inhibitors (TKI) retreatment in advanced/metastatic non-small-cell lung cancer (NSCLC) patients. We systematically searched PubMed, Embase, Cochrane databases, ASCO, and ESMO websites for studies evaluating EGFR-TKI retreatment in advanced/metastatic NSCLC patients. All analyses were performed using R software (v.4.2.2). We included 19 studies (9 CTs and 10 retrospective cohorts) with a total of 886 patients. In a pooled analysis of all patients during retreatment with TKI, median OS was 11.7 months (95% confidence interval [CI] 10.2–13.4 months) and PFS was 3.2 months (95% CI 2.5–3.9 months). ORR was 15% (95% CI 10–21%) and DCR was 61% (95% CI 53–67%). The subanalysis by generation of TKI in the rechallenge period revealed a slightly better ORR for patients on 3rd generation TKI (p = 0.05). Some limitations include the high heterogeneity of some of the analyses and inability to perform certain subanalyses. Our results unequivocally support the benefit of EGFR-TKI rechallenge in EGFR-mutated NSCLC patients progressing on TKI treatment after a TKI-free interval. These findings may be especially valuable in areas where access to novel therapeutic drugs and clinical trials is limited.

Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease. A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses. We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4 %; disease control rate [DCR], 94.4 %; and clinical benefit rate [CBR], 79.3 %) and a 12-month PFS of 64.7 % and OS of 82.7 %. Intracranial ORR, DCR, and CBR were seen in 62.2 %, 88.6 %, and 68.6 % of patients, respectively, and 67.4 % achieved intracranial PFS at 12 months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95 % confidence interval 1.3-10.8, p = 0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4 % and 94.1 % of patients, respectively. This updated meta-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.