Cancer Research and Treatment

Pemetrexed Maintenance versus Observation in Patients with Advanced Urothelial Carcinoma Who Completed First-Line Platinum-Based Chemotherapy without Disease Progression (PREMIER, KCSG GU16-05): Inkeun Park, Shinkyo Yoon, Ilhwan Kim, Kwonoh Park, Suee Lee, Bhumsuk Keam, Joo-Hwan Park, Jin Young Kim, Yoon Ji Choi, Byeong Seok Sohn, Jae Lyun Lee; Received October 16, 2024 Accepted December 26, 2024 Published online December 27, 2024; DOI: https://doi.org/10.4143/crt.2024.1003 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
Platinum-based chemotherapy is the standard treatment for advanced urothelial carcinoma (aUC). Switch maintenance therapy after first-line (1L) treatment may delay disease progression. This study evaluated pemetrexed as switch maintenance therapy versus observation in aUC patients without disease progression after initial chemotherapy.
Materials and Methods
Eligible aUC patients who did not progress after 4-6 cycles of cisplatin or carboplatin-based chemotherapy were randomized 1:1 to receive maintenance pemetrexed (500 mg/m² intravenously every 3 weeks, up to 16 cycles) or observation. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and safety.
Results
The trial was closed early due to slow accrual after avelumab approval. From October 2016 to December 2022, 97 patients were randomized to pemetrexed (n=49) or observation (n=48). The median age was 69 years (range, 43 to 90) and 66 (range, 33 to 82), respectively, with 63% and 73% of patients being male, respectively. The median PFS was 6.0 months (95% confidence interval [CI], 3.4 to 8.5) with pemetrexed versus 2.3 months (95% CI, 1.8 to 2.7) with observation (p=0.044; hazard ratio [HR], 0.64; 95% CI, 0.41 to 0.99). The median OS was 18.1 months (95% CI, 6.9 to 29.4) for pemetrexed and 17.9 months (95% CI, 16.1 to 19.7) for observation (p=0.913; HR, 1.03; 95% CI, 0.61 to 1.73). Common adverse events in the pemetrexed group included anemia (30.6%), fatigue (18.4%), and neutropenia (12.2%), primarily grade 1 or 2.
Conclusion
The PREMIER trial showed that switch maintenance pemetrexed significantly prolonged PFS in aUC patients post-1L platinum-based chemotherapy, with a favorable safety profile. Further studies on combination maintenance therapies are warranted.

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Gastrointestinal cancer

Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-analysis Based on Individual Patient-Level Data of Randomized Trials: Jaewon Hyung, Minsu Kang, Ilhwan Kim, Kyu-pyo Kim, Baek-Yeol Ryoo, Jaekyung Cheon, Hyewon Ryu, Ji Sung Lee, Ji-Won Kim, In Sil Choi, Jin Hyun Park, Ghassan K. Abou-Alfa, Jin Won Kim, Changhoon Yoo; Cancer Res Treat. 2025;57(2):519-527. Published online October 17, 2024; DOI: https://doi.org/10.4143/crt.2024.652

Abstract PDF Supplementary Material PubReader ePub

Purpose
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

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Liposomal irinotecan for previously treated patients with biliary tract cancer: A pooled analysis of NIFTY and NALIRICC trials
Changhoon Yoo, Anna Saborowski, Jaewon Hyung, Patrick Wenzel, Ilhwan Kim, Henning Wege, Kyu-pyo Kim, Gunnar Folprecht, Baek-Yeol Ryoo, Phillip Schütt, Jaekyung Cheon, Thorsten Götze, Hyewon Ryu, Ji Sung Lee, Arndt Vogel
Journal of Hepatology.2025;[Epub] CrossRef

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Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for More Than 1 Year: Youngun Kim, Jung Sun Kim, Beodeul Kang, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Yun Beom Sang, Sanghoon Jung, Chansik An, Chan Kim, Hong Jae Chon; Cancer Res Treat. 2024;56(4):1231-1239. Published online May 27, 2024; DOI: https://doi.org/10.4143/crt.2024.237

Abstract PDF Supplementary Material PubReader ePub: Purpose
Since 2020, atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year.
Materials and Methods
This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group.
Results
Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden < 25%, Eastern Cooperative Oncology Group 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p < 0.001; median time to onset [mTTO], 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO, 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO, 4.2 months), and proteinuria (69.6% vs. 38.4%, p < 0.001; mTTO, 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87.0% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment.
Conclusion
The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.

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