LBA73 Study EV-103 Cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC)

Rosenberg, Jacob; Milowsky, M.; Ramamurthy, Chethan; Mar, Nataliya; McKay, Rana R.; Friedlander, Terence W.; Ferrario, C.; Bracarda, Sergio; George, Saby; Moon, Helen; Geynisman, Daniel M.; Petrylak, Daniel P.; Borchiellini, Delphine; Burgess, Earle F.; Rey, José Pablo Maroto; Carret, A-S.; Yu, Yao; Guseva, M. V.; Moreno, Blanca Homet; O’Donnell, Peter H.

doi:10.1016/j.annonc.2022.08.079

Cited by 34 publications

(28 citation statements)

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“…Finally, microtubule-inhibitor payloads (maytansinoids, dolastatins, auristatins) and topoisomerase-I inhibitor payloads are able to directly induce dendritic cell activation [ 66 , 67 ]. Altogether, these evidence represent a strong rationale for combining ADCs and immunotherapy, a combination that could further augment the T cell infiltration within the tumor microenvironment [ 68 – 71 ].…”

Section: Future Adcs Combination Strategies In Breast Cancermentioning

confidence: 99%

Antibody–Drug Conjugate Revolution in Breast Cancer: The Road Ahead

Grinda

Rassy

Pistilli

2023

Curr. Treat. Options in Oncol.

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Opinion statementAntibody drug-conjugates (ADCs) have revolutionized the treatment of many types of cancer, including breast cancer. Recently, two new ADCs have been approved, trastuzumab deruxtecan and sacituzumab govitecan; both have demonstrated impressive improvements in overall survival, trastuzumab deruxtecan in all three subtypes of metastatic breast cancer and sacituzumab govitecan in luminal and triple negative metastatic breast cancer. These drugs are the results of significant progress and innovation in the construction of the three components of an ADC, the monoclonal antibody, the payload, and the linker, and of the discovery of new target antigens. ADC engineering has profoundly changed the paradigm of cancer treatment, on one side being effective on tumors considered inherently resistant to the payload class of drugs and on the other side demonstrating activity in tumors with very low target expression. Yet, it is likely that we are just at the beginning of a new era as the identification of new targets and the introduction of new ADC constructs and combinations will expand the field of ADC rapidly over the coming years.

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Section: Future Adcs Combination Strategies In Breast Cancermentioning

confidence: 99%

Antibody–Drug Conjugate Revolution in Breast Cancer: The Road Ahead

Grinda

Rassy

Pistilli

2023

Curr. Treat. Options in Oncol.

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“…For example, the EV-302 trial is investigating the efficacy of the Nectin-4 targeted antibody–drug conjugate enfortumab vedotin. In the EV-103 Phase 1b/2 trial in cisplatin-ineligible patients with previously untreated la/mUC (randomized Cohort K), enfortumab vedotin in combination with pembrolizumab demonstrated a clinically meaningful ORR of 64.5%, as did enfortumab vedotin monotherapy (ORR, 45.2%) [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC)

Bloudek¹,

Wright

McKay

et al. 2023

Current Oncology

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To compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC) with standard of care (SOC), a network meta-analysis (NMA) was conducted. A systematic literature review (SLR) identified phase 2 and 3 randomized trials investigating 1L treatment regimens in la/mUC published January 2001–September 2021. Three networks were formed based on cisplatin (cis) eligibility: cis-eligible/mixed (cis-eligible patients and mixed populations of cis-eligible/ineligible patients), cis-ineligible (strict; exclusively cis-ineligible patients), and cis-ineligible (wide; including studies with investigator’s choice of carbo). Analyses examined comparative efficacy by hazard ratio (HR) for overall survival (OS), and progression-free survival (PFS), and odds ratio (OR) for overall response rate (ORR), with 1L regimens vs. SOC. SOC was gemcitabine + cis (GemCis) or carboplatin (GemCarbo), cis-eligible/mixed network, and GemCarbo cis-ineligible networks. Of 1906 SLR identified citations, 55 trials were selected for data extraction. The NMA comprised 11, 6, and 8 studies in the cis-eligible/mixed, cis-ineligible (strict), cis-ineligible (wide) networks, respectively. In a meta-analysis of SOC control arms, median (95% CI) overall survival (OS) in months varied by network: 13.19 (12.43, 13.95) cis-eligible/mixed, 11.96 (10.43, 13.48) cis-ineligible (wide), and 9.74 (6.71, 12.76) cis-ineligible (strict). Most differences in OS, PFS, and ORR with treatment regimens across treatment networks were not statistically significant compared with SOC. Outcomes with current 1L regimens remain poor, and few significant improvements over SOC have been made, despite inclusion of recent clinical trial data, highlighting an unmet need in the la/mUC patient population.

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“…At the 2022 ESMO Congress, we saw initial results from cohort K of the EV-103 trial (ClinicalTrials.gov identifier: NCT03288545) which randomly assigned cisplatin-ineligible, previously untreated patients 1:1 to EV/pembrolizumab or EV alone. 12 Patients on the combination arm achieved a median ORR of 64.5%, and only 7.9% of evaluable patients had primary progressive disease. These are promising early efficacy signals supporting the excellent disease control achieved with EV/pembrolizumab.…”

Section: Clinical Challenges In Evaluation Treatment and Relevant Lit...mentioning

confidence: 93%

Platinum-Free Systemic Therapy in First-Line Metastatic Urothelial Carcinoma: Mirage or Oasis in the Platinum Desert?

Plimack

Zibelman

2023

JCO

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The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series was to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. The systemic treatment for metastatic urothelial carcinoma has evolved over the past decade; however, changes in the first-line setting have remained elusive and dependent on platinum-based chemotherapy regimens. Hoimes et al now present an update on the results of cohort A of the EV-103 phase Ib/II trial combining enfortumab vedotin and pembrolizumab in the first-line setting for patients with cisplatin-ineligible metastatic urothelial carcinoma. The efficacy results in this small, phase I cohort demonstrate an impressive response rate with the majority of patients deriving benefit in tumor control. In conjunction with the results from cohort K of EV-103, recently reported at the 2022 ESMO Congress, there is much anticipation regarding this combination as a future standard of care. However, despite this combination not including a traditional cytotoxic chemotherapeutic, it is still associated with potentially life-altering treatment-related toxicity, most notably rash and peripheral neuropathy, along with the risks of immune-related adverse events, which will need to be carefully calibrated for patients.

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LBA73 Study EV-103 Cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC)

Cited by 34 publications

References 0 publications

Antibody–Drug Conjugate Revolution in Breast Cancer: The Road Ahead

Antibody–Drug Conjugate Revolution in Breast Cancer: The Road Ahead

Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC)

Platinum-Free Systemic Therapy in First-Line Metastatic Urothelial Carcinoma: Mirage or Oasis in the Platinum Desert?

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