Cancer Research and Treatment

Original Articles

Bevacizumab Plus Erlotinib Combination Therapy for Advanced Hereditary Leiomyomatosis and Renal Cell Carcinoma-Associated Renal Cell Carcinoma: A Multicenter Retrospective Analysis in Korean Patients: Yeonjoo Choi, Bhumsuk Keam, Miso Kim, Shinkyo Yoon, Dalyong Kim, Jong Gwon Choi, Ja Young Seo, Inkeun Park, Jae Lyun Lee; Cancer Res Treat. 2019;51(4):1549-1556. Published online March 25, 2019; DOI: https://doi.org/10.4143/crt.2019.086

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Purpose
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic syndrome resulting from germline mutations in fumarate hydratase. The combination of bevacizumab plus erlotinib showed promising interim results for HLRCC-associated RCC. Based on these results, we analyzed the outcome of bevacizumab plus erlotinib in Korean patients with HLRCC-associated RCC.
Materials and Methods
We retrospectively reviewed the efficacy and safety of bevacizumab plus erlotinib in patients with HLRCC-associated RCC who were confirmed to have germline mutations in fumarate hydratase. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS) and overall survival (OS).
Result
We identified 10 patients with advanced HLRCC-associated RCC who received bevacizumab plus erlotinib. Median age at diagnosis was 41 years, and five of the patients had received the combination as first- or second-line treatments. The ORR was 50% and the median PFS and OS were 13.3 and 14.1 months, respectively. Most adverse events were predictable and manageable by conventional measures, except for one instance where a patient died of gastrointestinal bleeding.
Conclusion
This is the first real-world outcome of the treatment of advanced HLRCC-associated RCC. Bevacizumab plus erlotinib therapy showed promising activity with moderate toxicity. We should be increasingly aware of HLRCC-associated RCC and bevacizumab plus erlotinib should be a first-line treatment for this condition, unless other promising data are published.

Citations

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Application of the International Metastatic Renal Cell Carcinoma Database Consortium and Memorial Sloan Kettering Cancer Center Risk Models in Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma: A Multi-Institutional Retrospective Study Using the Korean Metastatic Renal Cell Carcinoma Registry: Jung Kwon Kim, Sung Han Kim, Mi Kyung Song, Jungnam Joo, Seong Il Seo, Cheol Kwak, Chang Wook Jeong, Cheryn Song, Eu Chang Hwang, Ill Young Seo, Hakmin Lee, Sung-Hoo Hong, Jae Young Park, Jinsoo Chung, Korean Renal Cell Carcinoma Study Group; Cancer Res Treat. 2019;51(2):758-768. Published online September 7, 2018; DOI: https://doi.org/10.4143/crt.2018.421

Abstract PDF Supplementary Material PubReader ePub

Purpose
The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and the Memorial Sloan Kettering Cancer Center (MSKCC) risk models were developed predominantly with clear cell renal cell carcinoma (RCC). Accordingly, whether these two models could be applied to metastatic non-clear cell RCC (mNCCRCC) as well has not been well-known and was investigated herein.
Materials and Methods
From the Korean metastatic RCC registry, a total of 156 patients (8.1%) with mNCCRCC among the entire cohort of 1,922 patients were analyzed. Both models were applied to predict first-line progression-free survival (PFS), total PFS, and cancer-specific survival (CSS).
Results
The median first-line PFS, total PFS, and CSS were 5, 6, and 24 months, respectively. The IMDC risk model reliably discriminated three risk groups to predict survival: the median firstline PFS, total PFS, and CSS for the favorable, intermediate, and poor risk groups were 9, 5, and, 2 months (p=0.001); 14, 7, and 2 months (p < 0.001); and 41, 21, and 8 months (p < 0.001), all respectively. The MSKCC risk model also reliably differentiated three risk groups: 9, 5, and, 2 months (p=0.005); 10, 7, and 3 months (p=0.002); and 50, 21, and 8 months (p < 0.001), also all respectively. The concordance indices were 0.632 with the IMDC model and 0.643 with the MSKCC model for first-line PFS: 0.748 and 0.655 for CSS.
Conclusion
The current IMDC and MSKCC risk models reliably predict first-line PFS, total PFS, and CSS in mNCCRCC.

Citations

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Pazopanib for the Treatment of Non-clear Cell Renal Cell Carcinoma: A Single-Arm, Open-Label, Multicenter, Phase II Study: Ki Sun Jung, Su Jin Lee, Se Hoon Park, Jae-Lyun Lee, Se-Hoon Lee, Jae Yun Lim, Jung Hun Kang, Suee Lee, Sun Young Rha, Kyung Hee Lee, Ho Young Kim, Ho Yeong Lim; Cancer Res Treat. 2018;50(2):488-494. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2016.584

Abstract PDF Supplementary Material PubReader ePub

Purpose
The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC.
Materials and Methods
Patientswith locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4weeks and tumorresponsewas evaluated every two cycles. The primary objective was overall response rate (ORR).
Results
A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay.
Conclusion
In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.

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