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

Bairi, Khalid El; Jarroudi, Ouissam Al; Afqir, Saïd

doi:10.1016/j.semcancer.2021.03.031

Cited by 15 publications

(10 citation statements)

References 122 publications

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“…EV-based measurement of tumor-derived biomarkers may be helpful in guiding clinical management through use in companion diagnostic applications. For example, folate receptor alpha, one of the ovarian cancer biomarkers included in the combination described in this study, is the target of several ongoing efforts focused on the development of antibody-drug-conjugate (ADC) therapeutics (El Bairi et al, 2021). A liquid biopsy assay indicative of the presence of folate receptor alpha positive tumors may be helpful in identifying patients more likely to respond to targeted ADC therapy.…”

Section: Resultsmentioning

confidence: 99%

Colocalization of Cancer Associated Biomarkers on Single Extracellular Vesicles for Early Cancer Detection

Salem

Bortolin

Couvillon

et al. 2023

Preprint

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Early detection of cancer remains a significant challenge. Existing liquid biopsy approaches to detect early-stage cancer show promise but suffer significant limitations including the abundance and stability of the analyte, large sample requirements, and insufficient specificity to distinguish biomarkers as originating from benign or cancerous cells. Extracellular vesicles (EVs) from cancer cells exhibit both stability and abundance in human biofluids which makes them an attractive target for early-cancer detection. Measurement of multiple, colocalized cancer-associated biomarkers on single EVs may improve upon existing methods for the non-invasive detection of cancer. To demonstrate this, we developed Mercy Halo(TM), an immunoassay designed to capture and detect cancer-specific biomarkers on the surface of EVs derived from cancer cells. Our platform shows promise for the sensitive and specific detection of early-stage ovarian tumors in human plasma, outperforming a single biomarker (CA125), for the detection of stage I and II high-grade serous ovarian cancer (HGSOC).

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Section: Resultsmentioning

confidence: 99%

Colocalization of Cancer Associated Biomarkers on Single Extracellular Vesicles for Early Cancer Detection

Salem

Bortolin

Couvillon

et al. 2023

Preprint

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“…Since ADCs have succeeded in treating other cancers, the use of this novel approach of targeting cytotoxic payloads to tumor cells is also being evaluated in PROC ( 73 ).…”

Section: Future Perspectivesmentioning

confidence: 99%

“…To date, the only ADC that has been evaluated for PROC in a pivotal trial is mirvetuximab soravtansine, an ADC that targets FRα, which is minimally expressed on normal tissues but overexpressed in >80% of epithelial ovarian tumors ( 73 – 75 ). In the open-label, phase 3 FORWARD I trial, mirvetuximab soravtansine did not meet its primary endpoint of PFS, but both ORR and OS favored mirvetuximab soravtansine over chemotherapy (ORR, 24% vs 10% [ P =.014]; OS, 17.3 vs 12.0 months [HR, 0.71; 95% CI, 0.49–1.02; [ P =.063]) in a subgroup of patients with high FRα expression, although these endpoints were not statistically significant ( 17 ).…”

Section: Future Perspectivesmentioning

confidence: 99%

Overcoming the challenges of drug development in platinum-resistant ovarian cancer

Eskander,

Moore,

Monk

et al. 2023

Front. Oncol.

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The definition of “platinum-resistant ovarian cancer” has evolved; it now also reflects cancers for which platinum treatment is no longer an option. Standard of care for platinum-resistant ovarian cancer is single-agent, non-platinum chemotherapy with or without bevacizumab, which produces modest response rates, with the greatest benefits achieved using weekly paclitaxel. Several recent phase 3 trials of pretreated patients with prior bevacizumab exposure failed to meet their primary efficacy endpoints, highlighting the challenge in improving clinical outcomes among these patients. Combination treatment with antiangiogenics has improved outcomes, whereas combination strategies with immune checkpoint inhibitors have yielded modest results. Despite extensive translational research, there has been a lack of reliable and established biomarkers that predict treatment response in platinum-resistant ovarian cancer. Additionally, in the platinum-resistant setting, implications for the time between the penultimate dose of platinum therapy and platinum retreatment remain an area of debate. Addressing the unmet need for an effective treatment in the platinum-resistant setting requires thoughtful clinical trial design based on a growing understanding of the disease. Recent cancer drug approvals highlight the value of incorporating molecular phenotypes to better define patients who are more likely to respond to novel therapies. Clinical trials designed per the Gynecologic Cancer InterGroup recommendations—which advocate against relying solely upon the platinum-free interval—will help advance our understanding of recurrent ovarian cancer response where platinum rechallenge in the platinum-resistant setting may be considered. The inclusion of biomarkers in clinical trials will improve patient stratification and potentially demonstrate correlations with biomarker expression and duration of response. With the efficacy of antibody-drug conjugates shown for the treatment of some solid and hematologic cancers, current trials are evaluating the use of various novel conjugates in the setting of platinum-resistant ovarian cancer. Emerging novel treatments coupled with combination trials and biomarker explorations offer encouraging results for potential strategies to improve response rates and prolong progression-free survival in this population with high unmet need. This review outlines existing data from contemporary clinical trials of patients with platinum-resistant ovarian cancer and suggests historical synthetic benchmarks for non-randomized trials.

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“…Most patients with ovarian cancer are diagnosed at an advanced stage (International Federation of Gynaecology and Obstetrics [FIGO] 2000 Stage III/IV), and over 75% of patients with late‐stage ovarian cancer die of the disease. Although the development of targeted therapies has gradually changed the prognosis of patients with platinum‐sensitive EOC, 3–6 effective treatments for patients with platinum‐resistant EOC are still lacking 7,8 . Therefore, chemotherapy is still the best therapeutic approach.…”

Section: Introductionmentioning

confidence: 99%

“…Although the development of targeted therapies has gradually changed the prognosis of patients with platinum‐sensitive EOC, 3 , 4 , 5 , 6 effective treatments for patients with platinum‐resistant EOC are still lacking. 7 , 8 Therefore, chemotherapy is still the best therapeutic approach. There is an urgent need to improve patient stratification for therapeutic strategies to overcome treatment resistance and search for new therapeutic targets for platinum resistance in patients with ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

High co‐expression of SLC7A11 and GPX4 as a predictor of platinum resistance and poor prognosis in patients with epithelial ovarian cancer

Shen

Qin

et al. 2022

BJOG

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

Cited by 15 publications

References 122 publications

Colocalization of Cancer Associated Biomarkers on Single Extracellular Vesicles for Early Cancer Detection

Colocalization of Cancer Associated Biomarkers on Single Extracellular Vesicles for Early Cancer Detection

Overcoming the challenges of drug development in platinum-resistant ovarian cancer

High co‐expression of SLC7A11 and GPX4 as a predictor of platinum resistance and poor prognosis in patients with epithelial ovarian cancer

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