Cabozantinib for previously treated radioiodine‐refractory differentiated thyroid cancer: Updated results from the phase 3 COSMIC‐311 trial

Brose, Marcia S.; Robinson, Bruce G.; Sherman, Steven I.; Jarząb, Barbara; Lin, Chia‐Chi; Vaisman, Fernanda; Hoff, Ana O.; Hitre, Erika; Bowles, Daniel W.; Sen, Suvajit; Oliver, Jennifer; Banerjee, Kamalika; Keam, Bhumsuk; Capdevila, Jaume

doi:10.1002/cncr.34493

Cited by 31 publications

(20 citation statements)

References 23 publications

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“…Patient disposition data have been previously published. 11 There were 96, 102, and 60 patients who received prior sorafenib only, prior lenvatinib only, and prior lenvatinib and sorafenib, respectively. Of these patients, 150 had papillary histology and 113 had follicular histology; 5 of these patients had both papillary and follicular histology and were included in both histology subgroups for analyses.…”

Section: Resultsmentioning

confidence: 99%

“…Grade 5 TEAEs not related to DTC that occurred ≤30 days after the last dose of the study treatment were reported in four patients receiving cabozantinib and one patient receiving placebo. 11 …”

Section: Resultsmentioning

confidence: 99%

“…COSMIC-311 demonstrated the benefit of cabozantinib as second- or third-line treatment after sorafenib, lenvatinib, or both. 10 , 11 COSMIC-311 was the first phase 3 study in RAIR DTC to include patients with prior lenvatinib treatment. A more detailed analysis of the benefit of cabozantinib based on prior treatment would interest physicians deciding on subsequent treatment for patients who progressed on first- or second-line VEGFR-targeted treatments.…”

Section: Introductionmentioning

confidence: 99%

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Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study

Capdevila,

Krajewska,

Hernando

et al. 2024

Thyroid®

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Background: Lenvatinib and sorafenib are standard of care first-line treatments for advanced, radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC). However, most patients eventually become treatment-resistant and require additional therapies. The phase 3 COSMIC-311 study investigated cabozantinib in patients with RAIR DTC who progressed on lenvatinib, sorafenib, or both and showed that cabozantinib provided substantial clinical benefit. Presented in this study is an analysis of COSMIC-311 based on prior therapy and histology. Methods: Patients were randomized 2:1 (stratification: prior lenvatinib [yes/no]; age [≤65, >65 years]) to oral cabozantinib (60 mg tablet/day) or matched placebo. Eligible patients received 1–2 prior vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors for DTC (lenvatinib or sorafenib required), had a confirmed DTC diagnosis, and were refractory to or ineligible for radioiodine therapy. For this analysis, progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by a blinded independent radiology committee were evaluated by prior therapy (lenvatinib only, sorafenib only, both) and histology (papillary, follicular, oncocytic, poorly differentiated). Results: Two hundred fifty-eight patients were randomized (170 cabozantinib/88 placebo) who previously received sorafenib only ( n = 96), lenvatinib only ( n = 102), or both ( n = 60). The median follow-up was 10.1 months. The median PFS (months) with cabozantinib/placebo was 16.6/3.2 (sorafenib only: hazard ratio [HR] 0.13 [95% confidence interval, CI, 0.06–0.26]), 5.8/1.9 (lenvatinib only: HR 0.28 [95% CI 0.16–0.48]), and 7.6/1.9 (both: HR 0.27 [95% CI 0.13–0.54]). The ORR with cabozantinib/placebo was 21%/0% (sorafenib only), 4%/0% (lenvatinib only), and 8%/0% (both). Disease histology consisted of 150 papillary and 113 follicular, including 43 oncocytic and 36 poorly differentiated. The median PFS (months) with cabozantinib/placebo was 9.2/1.9 (papillary: HR 0.27 [95% CI 0.17–0.43]), 11.2/2.5 (follicular: HR 0.18 [95% CI 0.10–0.31]), 11.2/2.5 (oncocytic: HR 0.06 [95% CI 0.02–0.21]), and 7.4/1.8 (poorly differentiated: HR 0.18 [95% CI 0.08–0.43]). The ORR with cabozantinib/placebo was 15%/0% (papillary), 8%/0% (follicular), 11%/0% (oncocytic), and 9%/0% (poorly differentiated). Safety outcomes evaluated were consistent with those previously observed for the overall population. Conclusions: Results indicate that cabozantinib benefits patients with RAIR DTC, regardless of prior lenvatinib or sorafenib treatments or histology. Clinical Trial Registration Number: NCT03690388.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study

Capdevila,

Krajewska,

Hernando

et al. 2024

Thyroid®

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“…There was no marked difference among the three types of cancer in terms of the incidence of proteinuria with VEGFR‐TKIs (Table 1). 12–37 In a meta‐analysis ( n = 9446) examining the incidence of proteinuria in clinical trials of five VEGFR‐TKIs (regorafenib, vandetanib, cabozantinib, lenvatinib, and axitinib) in patients with multiple carcinomas, including mRCC and HCC, the use of VEGFR‐TKIs significantly increased the relative risk (RR) of all‐grade proteinuria (RR 2.35, 95% confidence interval [CI] 1.69–3.27, p < 0.001) and high‐grade proteinuria (RR 3.70, 95% CI 2.09–6.54, p < 0.001) 2 . For each cancer type, the RR of proteinuria with VEGFR‐TKIs compared with the control arm was higher for HCC and mRCC for all‐grade proteinuria, and significantly higher for HCC and mRCC for high‐grade proteinuria.…”

Section: Frequency Of Proteinuria With Vegfr‐tkismentioning

confidence: 99%

Prevalence and management of proteinuria associated with vascular endothelial growth factor receptor‐targeted tyrosine kinase inhibitor treatment in advanced renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer

Kato,

Mizuno,

Miyake

2024

Int J of Urology

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Vascular endothelial growth factor receptor‐targeted tyrosine kinase inhibitors (VEGFR‐TKIs) are often used for treatment of several types of cancer; however, they are associated with an increased risk of proteinuria, sometimes leading to treatment discontinuation. We searched PubMed and Scopus to identify clinical studies examining the incidence and risk factors for proteinuria caused by VEGFR‐TKIs in patients with renal cell carcinoma, thyroid cancer, and hepatocellular carcinoma. The global incidence of proteinuria ranged from 6% to 34% for all grades of proteinuria, and from 1% to 10% for grade ≥3 proteinuria. The incidence of proteinuria did not differ significantly by cancer type, but in all three cancer types, there was a trend toward a higher incidence of proteinuria with lenvatinib than with other VEGFR‐TKIs. In terms of risk factors, the incidence of proteinuria was significantly higher among Asians (including Japanese) compared with non‐Asian populations. Other risk factors included diabetes mellitus, hypertension, and previous nephrectomy. When grade 3/4 proteinuria occurs, patients should be treated according to the criteria for dose reduction or withdrawal specified for each drug. For grade 2 proteinuria, treatment should be continued when the benefits outweigh the risks. Referral to a nephrologist should be considered for symptoms related to decreased renal function or when proteinuria has not improved after medication withdrawal. These management practices should be implemented universally, regardless of the cancer type.

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“…In recent years, research has continued to investigate the different treatment options for DTC patients (especially for those refractory to RAI) or for improving the tolerance of systemic therapies. Brose et al [76] published data regarding the phase 3 COSMIC-311 trial of 258 patients (170 treated with cabozantinib and 88 with placebo) who received cabozantinib for previously treated RAI-refractory DTC. The median PFS was 11.0 months (96% CI, 7.4-13.8 months) for cabozantinib and 1.9 months (96% CI, 1.9-3.7 months) for the placebo group (hazard ratio, 0.22; 96% CI, 0.15-0.32; p < 0.0001).…”

Section: New Perspectivesmentioning

confidence: 99%

Recurrent Differentiated Thyroid Cancer: The Current Treatment Options

Coca‐Pelaz

Rodrigo

Shah

et al. 2023

Cancers

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Differentiated thyroid carcinomas (DTC) have an excellent prognosis, but this is sometimes overshadowed by tumor recurrences following initial treatment (approximately 15% of cases during follow-up), due to unrecognized disease extent at initial diagnosis or a more aggressive tumor biology, which are the usual risk factors. The possible sites of recurrence are local, regional, or distant. Local and regional recurrences can usually be successfully managed with surgery and radioiodine therapy, as are some isolated distant recurrences, such as bone metastases. If these treatments are not possible, other therapeutic options such as external beam radiation therapy or systemic treatments should be considered. Major advances in systemic treatments have led to improved progression-free survival in patients previously considered for palliative treatments; among these treatments, the most promising results have been achieved with tyrosine kinase inhibitors (TKI). This review attempts to give a comprehensive overview of the current treatment options suited for recurrences and the new treatments that are available in cases where salvage surgery is not possible or in cases resistant to radioiodine.

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Cabozantinib for previously treated radioiodine‐refractory differentiated thyroid cancer: Updated results from the phase 3 COSMIC‐311 trial

Cited by 31 publications

References 23 publications

Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study

Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study

Prevalence and management of proteinuria associated with vascular endothelial growth factor receptor‐targeted tyrosine kinase inhibitor treatment in advanced renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer

Recurrent Differentiated Thyroid Cancer: The Current Treatment Options

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