Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Koshkin, Vadim S.; Bakaloudi, Dimitra Rafailia; Talukder, Rafee; Lin, Genevieve Ihsiu; Diamantopoulos, Leonidas; Jindal, Tanya; Vather-Wu, Naomi; Zakharia, Yousef; Tripathi, Nishita; Agarwal, Neeraj; Dawsey, Scott J.; Gupta, Shilpa; Lu, Eric; Drakaki, Alexandra; Liu, Sandy; Zakopoulou, Roubini; Bamias, Aristotelis; Fulgenzi, Claudia-Maria; Cortellini, Alessio; Pinato, David J.; Barata, Pedro C.; Grivas, Petros; Khaki, Ali Raza; Koshki, Vadim S.

doi:10.1016/j.clgc.2022.11.003

Cited by 12 publications

(7 citation statements)

References 37 publications

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“…Further investigation into potential re-challenge is warranted given these results and recent implications if ICI rechallenge in UC. 37 Taken together, these results substantiate the notion that irAEs may indeed serve as prognostic markers of beneficial response and outcomes in urothelial cancer. Additionally, the specific association of dermatologic irAEs with improved outcomes aligns with trends seen in other thoroughly studied cancers treated with ICIs.…”

Section: Discussionsupporting

confidence: 74%

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors

et al. 2023

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Background In advanced urothelial cancers (UC), immune checkpoint inhibitors (ICI) show promise as a durable therapy. Immune-related adverse events (irAEs), a side effect of ICIs, may serve as an indicator of beneficial response. We investigated the relationship between irAEs and clinical outcomes in patients with advanced UC who received ICI. Materials and Methods In this retrospective study, we investigated 70 patients with advanced UC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on patients were collected through chart review. Cox’s proportional hazard model and logistic regression were applied to estimate the association with overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). The possible lead-time bias was handled in extended Cox regression models. Results The median age of the cohort was 68. Over one-third (35%) of patients experienced an irAE, with skin being the most frequent organ involved (12.9%). Patients that experienced at least one irAE had significantly enhanced OS (HR: 0.38, 95% CI, 0.18-0.79, P = .009), PFS (HR: 0.27, 95% CI, 0.14-0.53, P < .001), and CB (OR: 4.20, 95% CI, 1.35-13.06, P = .013). Patients who experienced dermatologic irAEs also had significantly greater OS, PFS, and CB. Conclusion Of patients with advanced UC that had undergone ICI therapy, those who had irAEs, especially dermatologic irAEs, had significantly greater OS, PFS, and CB. These results may suggest that irAE’s may serve as an important marker of durable response to ICI therapy in urothelial cancer. The findings of this study need to be validated with larger cohort studies in the future.

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Section: Discussionsupporting

confidence: 74%

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors

et al. 2023

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“…There were 26 original studies on patients’ subgroups from primary cohorts, 2 case series (≤4) and 3 case reports. There were 812 patients diagnosed with several cancers including melanoma (13 studies) [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], non-small cell lung cancer (NSCLC; 9 studies) [ 17 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ], breast cancer (1 study) [ 45 ], renal cell carcinoma (1 study) [ 46 ], mesothelioma (1 study) [ 16 ], classic Hodgkin lymphoma (cHL; 1 study) [ 47 ], head and neck cancers (1 study) [ 48 ], urothelial carcinoma [ 49 ] and mixed cancers (3 studies) [ 15 , 50 , 51 ]. Additionally, we included 1 retreated melanoma patient from the Department of Oncology and Radiotherapy at the University Clinical Centre of Medical University of Gdansk ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

The Effectiveness of Cancer Immune Checkpoint Inhibitor Retreatment and Rechallenge—A Systematic Review

Perdyan

Sobocki

Balihodzic

et al. 2023

Cancers

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Despite a great success of immunotherapy in cancer treatment, a great number of patients will become resistant. This review summarizes recent reports on immune checkpoint inhibitor retreatment or rechallenge in order to overcome primary resistance. The systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was performed using PubMed, Web of Science and Scopus. In total, 31 articles were included with a total of 812 patients. There were 16 retreatment studies and 13 rechallenge studies. We identified 15 studies in which at least one parameter (overall response rate or disease control rate) improved or was stable at secondary treatment. Interval treatment, primary response to and the cause of cessation for the first immune checkpoint inhibitors seem to be promising predictors of secondary response. However, high heterogeneity of investigated cohorts and lack of reporting guidelines are limiting factors for current in-depth analysis.

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“…This finding implies that a limited subset of patients rechallenged with an ICI may experience clinical benefits, but whether enfortumab vedotin with pembrolizumab will provide additional benefit compared with single-agent enfortumab needs to be explored. Clinical trials are essential to address this crucial question . For patients for whom enfortumab vedotin with pembrolizumab is not a viable option, an alternative choice is nivolumab in combination with gemcitabine and cisplatin.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical trials are essential to address this crucial question. 42 For patients for whom enfortumab vedotin with pembrolizumab is not a viable option, an alternative choice is nivolumab in combination with gemcitabine and cisplatin.…”

Section: Jama Network Open | Oncologymentioning

confidence: 99%

“…Nevertheless, it remains uncertain whether enfortumab vedotin with pembrolizumab is the optimal choice for patients who have undergone prior anti-PD-1 therapy in the adjuvant setting. Makrakis et al 42 conducted a retrospective study revealing that patients receiving a second immune checkpoint inhibitor (ICI) after progression during initial ICI treatment demonstrated an overall response rate of 13%. This finding implies that a limited subset of patients rechallenged with an ICI may experience clinical benefits, but whether enfortumab vedotin with pembrolizumab will provide additional benefit compared with single-agent enfortumab needs to be explored.…”

Section: Jama Network Open | Oncologymentioning

confidence: 99%

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Treatment Patterns and Attrition With Lines of Therapy for Advanced Urothelial Carcinoma in the US

Mathew Thomas,

Jo,

Tripathi

et al. 2024

JAMA Netw Open

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ImportanceThe treatment paradigm for advanced urothelial carcinoma (aUC) has undergone substantial transformation due to the introduction of effective, novel therapeutic agents. However, outcomes remain poor, and little is known about current treatment approaches and attrition rates for patients with aUC.ObjectivesTo delineate evolving treatment patterns and attrition rates in patients with aUC using a US-based patient-level sample.Design, Setting, and ParticipantsThis retrospective cohort study used patient-level data from the nationwide deidentified electronic health record database Flatiron Health, originating from approximately 280 oncology clinics across the US. Patients included in the analysis received treatment for metastatic or local aUC at a participating site from January 1, 2011, to January 31, 2023. Patients receiving treatment for 2 or more different types of cancer or participating in clinical trials were excluded from the analysis.Main Outcomes and MeasuresFrequencies and percentages were used to summarize the (1) treatment received in each line (cisplatin-based regimens, carboplatin-based regimens, programmed cell death 1 and/or programmed cell death ligand 1 [PD-1/PD-L1] inhibitors, single-agent nonplatinum chemotherapy, enfortumab vedotin, erdafitinib, sacituzumab govitecan, or others) and (2) attrition of patients with each line of therapy, defined as the percentage of patients not progressing to the next line.ResultsOf the 12 157 patients within the dataset, 7260 met the eligibility criteria and were included in the analysis (5364 [73.9%] men; median age at the start of first-line treatment, 73 [IQR, 66-80] years). All patients commenced first-line treatment; of these, only 2714 (37.4%) progressed to receive second-line treatment, and 857 (11.8%) advanced to third-line treatment. The primary regimens used as first-line treatment contained carboplatin (2241 [30.9%]), followed by PD-1/PD-L1 inhibitors (2174 [29.9%]). The PD-1/PD-L1 inhibitors emerged as the predominant choice in the second- and third-line (1412 of 2714 [52.0%] and 258 of 857 [30.1%], respectively) treatments. From 2019 onward, novel therapeutic agents were increasingly used in second- and third-line treatments, including enfortumab vedotin (219 of 2714 [8.1%] and 159 of 857 [18.6%], respectively), erdafitinib (39 of 2714 [1.4%] and 28 of 857 [3.3%], respectively), and sacituzumab govitecan (14 of 2714 [0.5%] and 34 of 857 [4.0%], respectively).Conclusions and RelevanceThe findings of this cohort study suggest that approximately two-thirds of patients with aUC did not receive second-line treatment. Most first-line treatments do not include cisplatin-based regimens and instead incorporate carboplatin- or PD-1/PD-L1 inhibitor–based therapies. These data warrant the provision of more effective and tolerable first-line treatments for patients with aUC.

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Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Cited by 12 publications

References 37 publications

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors

The Effectiveness of Cancer Immune Checkpoint Inhibitor Retreatment and Rechallenge—A Systematic Review

Treatment Patterns and Attrition With Lines of Therapy for Advanced Urothelial Carcinoma in the US

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