Khalid El Bairi

New horizons for platinum-resistant ovarian cancer: insights from the 2023 American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) Annual Meetings

Platinum-resistant ovarian cancer is difficult to treat and has a poor prognosis. Patients with platinum-resistant ovarian cancer have limited treatment options and often have a limited benefit from existing chemotherapeutic agents. There is a lack of contemporary effective anticancer drugs and reliable predictive biomarkers for this aggressive cancer. Recent cutting-edge research presented at the 2023 American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) Annual Meetings has provided insights into several potential therapeutic targets, such as DNA damage repair proteins, cell-cycle regulators, and immune-modulating agents. In addition, antibody-drug conjugates have provided new practice-changing results in platinum-resistant ovarian cancer. Here, we review the results of research presented at this annual event, with a focus on clinical trials investigating novel treatment approaches for platinum-resistant ovarian cancer, in addition to predictive and prognostic biomarkers for optimal patient selection, and other topics, such as real-world evidence.

The OVANORDEST project: making an impact on ovarian cancer in Morocco

Is HE4 Superior over CA-125 in the Follow-up of Patients with Epithelial Ovarian Cancer?

Notwithstanding important advances in the treatment of epithelial ovarian cancer (EOC), this disease is still a leading cause of global high mortality from gynecological malignancies. Recurrence in EOC is inevitable and it is responsible for poor survival rates. There is a critical need for novel effective biomarkers with improved accuracy compared to the standard carbohydrate antigen-125 (CA-125) for follow-up. The human epididymis protein 4 (HE4) is used for early detection of EOC (ROMA algorithm) as well as for predicting optimal cytoreduction after neoadjuvant chemotherapy and survival outcomes. Notably, the emerging HE4 is a promising prognostic biomarker that has displayed better accuracy in various recent studies for detecting recurrent disease. In this mini-review, we discussed the potential of HE4 as an accurate predictor of EOC recurrence.

Revisiting antibody-drug conjugates and their predictive biomarkers in platinum-resistant ovarian cancer

Until to date, platinum derived drugs are still the backbone of treating ovarian cancer (OC). Most patients treated with platinum-based chemotherapy develop resistance during the course of their management. The treatment of platinum-resistant ovarian cancer (PROC) is challenging. Few therapeutic options are available for patients with this aggressive disease. Besides, there are liminal advances regarding new anticancer drugs as well as validated predictive biomarkers of clinical outcomes in this setting. The enrollment of PROC patients in interventional studies is limited as compared to newly launched clinical trials for platinum-sensitive OC. Enthusiastically, the emergence of antibody-drug conjugates (ADCs) has provided promising findings for further clinical development in PROC. ADCs have the advantage to selectively deliver cytotoxic drugs to cancer cells expressing several of antigens using specific monoclonal antibodies based on the concept of immune bioconjugation. This innovative class of therapeutics showed encouraging early signs of clinical efficacy in PROC particularly mirvetuximab soravtansine that has been successfully introduced into three randomized and controlled phase III studies. In this review, the evidence from clinical trials supporting the development of ADCs targeting folate receptor alpha, sodium-dependent phosphate transporter 2B, dipeptidase 3, mesothelin, mucin 16, and tissue factor using various cytotoxic payloads in PROC is reviewed.

Does the “Devil” originate from the fallopian tubes?

Epithelial ovarian cancer (OC) is a heterogeneous disease and continues to be mostly diagnosed in advanced stages. The high lethality, the high rate of platinum-resistance, and the poor survival outcomes are the principal factors for categorizing OC among the most aggressive gynecological cancers. Only recently, a substantial progress has been made in our latest understanding of the origins of OC, particularly of high-grade serous histology. For a long time, the accumulation of genetic alterations in epithelial single layer cells of ovarian cysts caused by cyclic ovulations was considered as the most important driver and the long-standing dogma of ovarian tumorigenesis. Besides, the unique biological features and high histological heterogeneity of OC did not support this hypothesis. Indeed, various extra-ovarian cells of origin and multiple sites to each histotype were proposed, supported by cogent evidence from clinical cohorts and animal studies. In light of this enigma, this review was conducted to discuss the recent evidence supporting the revised origins of ovarian carcinoma histotypes with a particular focus on high-grade serous OC which may impact diagnostic and preventive approaches.

Exploring the prognostic impact of tumor sidedness in ovarian cancer: A population-based survival analysis of over 10,000 patients

Very recently, emerging evidence demonstrated that laterality might be an independent prognostic factor in patients with advanced ovarian cancer (OC). Based on preliminary provocative observations, our study aimed to investigate the prognostic impact of sidedness in a large cohort of women with OC. Survival was estimated based on Kaplan-Meier method and survival curves were compared using Log-rank test. Cox proportional-hazards model was used to study the association between survival and covariates. A total of 10,177 women with OC were included. Mean age at diagnosis was 59.58 years (±13.5); 36.7% OC right-sided, 36.9% were left- sided, and 26.4% had bilateral OC. The median overall survival (OS) for the entire population was 77 months, with the lowest median OS observed in bilateral OC (median OS: 34 months). The prognostic value of OC sidedness was not confirmed at the univariable analysis (HR = 0.958; 95% CI: 0.888-1.033, p = 0.268). However, women with bilateral OC has a 45% higher risk of death as compared with unilateral diagnosis (HR = 1.453; 95% CI: 1.410-1.497; p< 0.001). The independent prognostic value was further confirmed on multivarible analysis after adjusting for covariates including age, marital status, histological type, CA-125 at diagnosis, grade, stage, chemotherapy and surgery (HR = 1.087; 95% CI: 1.043-1.136, p = 0.02). However, the ultimate prognostic significance appeared less prominent, with bilateral OC conferring a relative increase of 8.7% of mortality. Our real-world study demonstrated that impact of tumor sidedness has no prognostic implication (right vs left OC) but bilateral OCs might be marginally more prognostically unfavorable. Prospective validation might be warranted, to confirm the prognostic significance of OC sidedness, including for the presence of key genetic alterations and lymph nodes asymmetry, to better stratify patients with OC and predict outcomes according to tumor sidedness at diagnosis.