Stereotactic Body Radiotherapy as a Salvage Therapy after Incomplete Radiofrequency Ablation for Hepatocellular Carcinoma: A Retrospective Cohort Study

Residual tumor tissue after radiofrequency ablation (RFA) is inevitable in clinical practice, and the optimal management of residual tumor after RFA has not been established. To evaluate the efficiency and toxicity of stereotactic body radiotherapy (SBRT) as a salvage therapy after incomplete RFA for hepatocellular carcinoma (HCC), we retrospectively included 32 HCC patients with an initial incomplete response (iIR) to RFA from May 2011 to August 2018. An iIR was defined as the presence of residual enhancement on CT or MRI one month after RFA treatment. The primary endpoint was local tumor control (LTC); the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. All patients fulfilled 6 fractions of SBRT as planned, with dosages ranging from 30 Gy to 54 Gy. The objective response rate (ORR) was 50.0%. The 1- and 2-year LTC rates were 86.6% (95% CI, 74.3% to 98.9%) and 74.7% (95% CI, 55.9% to 93.5%), respectively. Fewer times of prior treatments was associated with better LTC (HR = 11.7, P=0.026). The 1- and 2-year PFS rate were 69.9% (95% CI, 53.4% to 86.4%) and 52.7% (95% CI, 33.1% to 72.3%), respectively. A higher Child-Pugh score was the only independent risk factor for tumor progression (HR = 5.17, P=0.012). The 1- and 3-year OS rate were 85.6% and 67.1%, respectively. Only two patients suffered grade 3 adverse events, and none experienced grade 4 or 5 events. In conclusion, for HCC patients confirmed to have an iIR to prior RFA, with compensated liver function, SBRT provided favorable LTC and OS along with acceptable toxicity.

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Dose-escalated external beam radiotherapy in unresectable hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.267 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 267-267

Author(s):

H. D. Skinner ◽

H. J. Sharp ◽

A. O. Kaseb ◽

M. M. Javle ◽

J. Vauthey ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Viral Hepatitis ◽

External Beam Radiotherapy ◽

Progression Free Survival ◽

Residual Tumor ◽

Local Tumor Control ◽

Tumor Control ◽

External Beam ◽

Grade 3 ◽

One Year

267 Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Data regarding the use of external beam radiotherapy is limited in patients from populations without endemic viral hepatitis. We examine the outcomes for patients treated with external beam radiotherapy in the modern era at a single institution. Methods: A total of 29 patients with localized HCC treated from 2000 to 2009 were reviewed. Patients with metastatic disease at the time of radiation were excluded. Median radiation dose was 50 Gy (range 30-75 Gy) with a median biologically effective dose (BED) of 80.6 (range 60-138.6). Median tumor size at the time of radiation was 5.2 cm (range 2-25 cm). Results: Median residual tumor following radiation was 80% (range 27%-278%), with a median residual α-fetoprotein of 47% (range 0.8%-8240%). Estimated one-year overall survival (OS) and in-field progression-free survival (PFS) rates for the study population were 56% and 79%, respectively. One year OS in patients treated to a BED <75 was 18% vs. 69% in patients treated to a BED ≥75 (p=0.002). One year in-field PFS rate (60% vs. 88%, p=0.023) and biochemical PFS duration (median 6.5 vs. 1.6 mos., p=0.001) were also significantly improved in patients treated to a BED ≥75. Grade 3 toxicity was seen in only 13.8% of patients. Conclusions: In a population without endemic viral hepatitis, unresectable HCC demonstrates significant response toexternal beam radiotherapy with minimal toxicity. Furthermore, our findings suggest that increased BED is associated with improved survival and local tumor control. No significant financial relationships to disclose.

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Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

Digestive Diseases ◽

10.1159/000480257 ◽

2017 ◽

Vol 35 (6) ◽

pp. 611-617 ◽

Cited By ~ 9

Author(s):

Kazuomi Ueshima ◽

Naoshi Nishida ◽

Masatoshi Kudo

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Progression Free Survival ◽

Sequential Therapy ◽

Advanced Hepatocellular Carcinoma ◽

Open Label ◽

Effective Treatment Option ◽

Sorafenib Treatment ◽

Advanced Hcc ◽

Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

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Sorafenib versus cytotoxic chemotherapy for patients with advanced hepatocellular carcinoma: A retrospective, single-institution study.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.339 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 339-339

Author(s):

S. Lee ◽

S. Yoon ◽

S. Shin ◽

H. Choi

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Progression Free Survival ◽

Cytotoxic Chemotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Chemotherapy Group ◽

Sorafenib Group ◽

The Difference ◽

Grade 3 ◽

Novel Target

339 Background: Prior to the sorafenib era, most of the advanced hepatocellular carcinoma (HCC) patients had to rely only on conventional cytotoxic chemotherapy. But the introduction of sorafenib in 2008 had given HCC patients additional option for their treatment. However, given that sorafenib has been a nonreimbursable drug under the Korea public health system, most of treatment strategy has largely been determined by patients' affordability of the drug rather than by difference in efficacy and toxicity of the two treatments. Therefore, we compared the efficacy and toxicity of the two treatments by observing HCC patients. Methods: From January 2002 to December 2009, 173 patients with unresectable HCC had been retrospectively analyzed. Among them, 44 (25.4%) had been treated with sorafenib and the remaining had received cytotoxic chemotherapy. We evaluated objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: The median OS of sorafenib group was 23.0 weeks (95% CI, 8.1-37.9) vs. 43.6 weeks (95% CI, 34.0-37.9) for cytotoxic chemotherapy group. The median PFS for sorafenib group was 11.1 weeks (95% CI, 6.5-15.8) versus 12.4 weeks (95% CI, 8.1-16.7) for cytotoxic chemotherapy group. However, the difference in both findings had not been statistically significant (p=0.105 and p=0.496, respectively). ORR and DCR for sorafenib group were 2.3% and 52.3% versus 6.2% and 43.4% for cytotoxic chemotherapy group, respectively. Patients treated with chemotherapy had shown higher frequencies of grade 3 or 4 neutropenia, 19.7%, (vs. 0% for sorafenib). However, the group with sorafenib had reported a higher rate of all grade dermatologic toxicities such as hand-foot skin reaction, rash and pruritus. Conclusions: Our analysis indicates that efficacy of conventional chemotherapy is not inferior to that of sorafenib. Further research including novel target agent and cytotoxic chemotherapy is needed to improve clinical outcomes for advanced HCC. No significant financial relationships to disclose.

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Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma and other pediatric solid malignancies: A European ITCC study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9517 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9517-9517

Author(s):

Angela Di Giannatale ◽

Kieran Mc Hugh ◽

Nathalie Dias ◽

Annick Devos ◽

Birgit Geoerger ◽

...

Keyword(s):

Solid Tumors ◽

Phase Ii ◽

Topoisomerase I ◽

Phase Ii Study ◽

Alkylating Agents ◽

Objective Response ◽

Progression Free Survival ◽

Tumor Control ◽

Disease Stabilization ◽

Grade 3

9517 Background: Temozolomide and topotecan have shown activity in several pediatric cancers, including neuroblastoma. Resistance to alkylating agents due to MGMT expression, MMR deficiency or microsatellite instability may be overcome through the combination with topoisomerase I inhibitors. The combination of temozolomide and topotecan (TOTEM) was well tolerated and showed preliminary activity in children with neuroblastoma and glioma (Rubie et al, 2010). Methods: This multicenter, non-randomized, multi-cohort Phase II study included children with neuroblastoma according to a 2-stage Simon design, and patients with central nervous system (CNS) and extra-cranial solid tumors in a descriptive design. Temozolomide was administered orally at 150 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously for 5 consecutive days every 28 days. The main endpoint was objective response (OR), i.e., Complete or Partial Response (CR+PR), evaluated after 2 cycles according to WHO criteria, or INRC criteria for neuroblastoma patients with mIBG-positive lesions, by an independent radiological review. Independent review of mIBG imaging is pending. Results: 103 patients, median age 9.4 years (range 1-21), were treated between June 2009 and May 2011 in 18 centers: 38 neuroblastoma, 33 CNS tumors and 32 other solid tumors. Overall 420 cycles were administered (median 3 per patient; range 1-12). Grade 3 or 4 neutropenia was frequent (55% courses), though only 6% of patients developed febrile neutropenia. In the neuroblastoma cohort, 1 CR and 7 PR were observed, leading to an estimated OR rate of 21% (95%CI, 10-37%). Additionally 22 patients had disease stabilization (SD), leading to an overall tumor control (CR+PR+SD) of 79% (63-90%), and a 12-month progression-free survival rate of 47% (31-64%). Overall, 17/102 evaluable patients achieved an OR (17%, 10-25%), with 1 CR and 3 PR in 9 medulloblastoma (44%, 14-79%), 2 PR in 4 PNET, 1 PR in 12 malignant glioma, and 2 PR in 9 RMS. Conclusions: Temozolomide-topotecan combination results in significant tumor control in children with neuroblastoma and medulloblastoma/PNET with favorable toxicity profile.

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Stereotactic Body Radiotherapy as a Salvage Therapy after Incomplete Radiofrequency Ablation for Hepatocellular Carcinoma: A Retrospective Propensity Score Matching Study

Cancers ◽

10.3390/cancers11081116 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1116 ◽

Cited By ~ 3

Author(s):

Yang-Xun Pan ◽

Mian Xi ◽

Yi-Zhen Fu ◽

Dan-Dan Hu ◽

Jun-Cheng Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Propensity Score ◽

Disease Progression ◽

Propensity Score Matching ◽

Stereotactic Body Radiotherapy ◽

Progression Free Survival ◽

Progression Rate ◽

Local Disease ◽

Disease Progression Rate

Abstract: (1) Background: To investigate the clinical outcomes between radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) for residual hepatocellular carcinoma (RHCC). (2) Methods: 139 patients were diagnosed with the RHCC after post-operative checkup, among whom 39 and 33 patients underwent RFA or SBRT as salvage treatments, respectively. We applied the propensity score matching (PSM) to adjust for imbalances in treatment assignment. Local disease progression, progression-free survival (PFS), overall survival (OS), and treatment-related side effects were the study endpoints. (3) Results: Before PSM, the SBRT group demonstrated significantly lower local disease progression rate (6/33 vs. 23/39; p = 0.002), better PFS (the 1- and 3-year PFS were 63.3% and 49.3% vs. 41.5% and 22.3%, respectively, p = 0.036), and comparable OS (the 1- and 3-year OS were 85.4% and 71.1% vs. 97.3% and 57.6%, respectively, p = 0.680). After PSM of 23 matched cases, the SBRT group demonstrated significantly lower local disease progression rate, better PFS and comparable OS. Centrally located tumor predicted the worse OS. No acute grade 3+ toxicity was observed in both groups. (4) Conclusion: SBRT might be the preferred treatment for RHCC, especially for patients with larger tumors or tumors abutting major vessels, rather than repeated RFA.

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HIFU for the treatment of difficult colorectal liver metastases with unsuitable indications for resection and radiofrequency ablation: A phase I clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16715 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16715-e16715

Author(s):

Tong Yang

Keyword(s):

Radiofrequency Ablation ◽

Liver Metastases ◽

Colorectal Liver Metastases ◽

Focused Ultrasound ◽

Objective Response ◽

Progression Free Survival ◽

Complete Response ◽

High Intensity Focused Ultrasound ◽

Hifu Treatment ◽

Grade 3

e16715 Background: Previous studies showed that high intensity focused ultrasound (HIFU) treatment could treat liver tumor and pancreatic cancer, with fewer serious adverse reactions.To evaluate the safety and efficacy of HIFU for patients with colorectal liver metastases(CRLM) that were contraindicated for resection and radiofrequency ablation. Methods: Patients between 20 to 80 years of age with 1-3 liver metastases from colorectal cancer were included. The primary colorectal lesions were thoroughly resected and any case with extra-hepatic metastasis was excluded. Ultrasound guided HIFU system was employed and target region ablation was achieved with repeated sonications from the deep to shallow regions of the tumor section by section. Results: Thirteen patients were enrolled. Pain was the most common adverse events(AEs) (n = 8), followed by fatigue (n = 7), increased aspartate aminotransferase (AST) (n = 7), increased alanine aminotransferase(ALT) (n = 5), and skin edema (n = 4). No grade≥3 AEs occurred.The majority of patients (76.9%) had a complete response and the remaining three patients achieved partial response. The objective response rate was 100% after the first HIFU treatment. Nine patients relapsed but most were isolated only in the liver (8/9). The median follow-up was 25 months. The 2-year progression-free survival (PFS) was 16.7%, and median PFS was 9 months. Notably, the 2-year overall survival (OS) was 77.8%, and median OS was 25 months. Conclusions: This study indicates that HIFU treatment is safe, has an excellent tumor response and long-termprognosis even when the foci in risky locations, and is probably a considerable option for patients who were unsuitable for other local treatments.

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Upfront or add-on combination therapeutic strategy exploration in unresectable hepatocellular carcinoma using sorafenib plus sintilimab: A retrospective analysis of real-world evidence.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16135 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16135-e16135

Author(s):

Jiamin Cheng ◽

Yinyin Li ◽

Tong Wu ◽

Zhen Zhang ◽

Yan Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Kinase Inhibitor ◽

Objective Response ◽

Progression Free Survival ◽

Second Line ◽

First Line ◽

First Line Therapy ◽

Treatment Naïve ◽

Inhibitor Regimen ◽

Grade 3

e16135 Background: Recently, tyrosine kinase inhibitor plus PD-1 inhibitor regimen has shown promising effects on hepatocellular carcinoma (HCC). So far, no study explored the effectiveness of upfront versus add-on combination therapy in patients with systemic treatment-naïve and treatment-experienced HCCThis study aimed to explore the effectiveness and safety of sintilimab combined sorafenib in patients with untreated or sorafenib monotherapy-refractory unresectable HCC. Methods: In this retrospective study, unresectable HCC patients received sintilimab plus sorafenib from January 2018 to December 2020 were enrolled. According to the prior treatment, patients were grouped as first-line and second-line (received sorafenib combined sintilimab after progression on sorafenib alone). Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), safety, and the change of Child-Pugh score from baseline to progression were recorded. The PFS was defined as the time from first dosing of sintilimab until disease progressive or death. Results: A total of 31 patients were reviewed, including 19 patients in first-line group and 12 patients in second-line group. There were two patients with Barcelona Clinic Liver Cancer (BCLC) stage B and 17 patients with BCLC stage C in first-line group, and one patient with BCLC stage A and 11 patients with BCLC stage C in second-line group, respectively. The ORR and DCR were 27.8% and 77.8% in first-line group, and 16.7% and 75.0% in second-line group, respectively. Fourteen cases in first-line group and 10 cases in second-line group showed PD during the follow-up. The 6-month PFS rate of first-line group and second-line group were 47.1% and 64.8%, respectively. Thirteen and 9 patients experienced AE in two groups. Four and 2 grade 3 AEs occurred in two groups, respectively. The most frequency AE were hand-foot-skin reaction in both group (58.0% and 50.0%, respectively). One patient discontinued sintilimab due to AE in second-line group. Among PD patients, the Child-Pugh score improved in 2 cases, maintained in 5 cases, and deteriorated in 7 cases in the first-line group; and improved in 3 cases, miantained in 3 cases, and deteriorated in 4 cases in the second-line group. Conclusions: Sorafenib plus sintilimab showed potential anti-tumor effect and tolerance on unresectable HCC, either as first-line therapy or after progression with sorafenib monotherapy. Outcomes.[Table: see text]

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Real-Life Clinical Practice with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Center Experience Second Analysis

Digestive Diseases ◽

10.1159/000439079 ◽

2015 ◽

Vol 33 (6) ◽

pp. 728-734 ◽

Cited By ~ 5

Author(s):

Tadaaki Arizumi ◽

Kazuomi Ueshima ◽

Mina Iwanishi ◽

Hirokazu Chishina ◽

Masashi Kono ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Response ◽

Objective Response ◽

Real Life ◽

Progression Free Survival ◽

University Hospital ◽

Phase Iii ◽

Advanced Hepatocellular Carcinoma ◽

Single Center ◽

Grade 3

Objectives: Sorafenib has become a standard therapy for advanced hepatocellular carcinoma following the demonstration of significant increase in progression-free survival as well as overall survival (OS) in the 2-phase III trials. We examined efficacy and adverse events (AEs) in patients treated with sorafenib over a 6-year period since approval in Japan. Methods: Two hundred and forty-one patients treated with sorafenib at the Kinki University Hospital were retrospectively analyzed clinically for the factors related to survival periods, tumor response evaluated by the Response Evaluation Criteria In Cancer of the Liver (RECICL) and AEs. Results: OS was 14.3 months. According to the RECICL, the objective response and disease control rates were 18.6% (43 of 241) and 61.1% (137 of 241), respectively. AEs were seen in 77.3% (187 of 241), with Grade 3 or higher in 23.6% (57 of 241). The most frequent AE was hand-foot skin reaction in 109 patients (45.0%), and 28 patients (11.8%) showed Grade 3 or higher. Significant factors contributing to the OS were treatment duration (p = 0.0204), up-to-7 criteria (p = 0.0400), increase of Child-Pugh score (p = 0.0008) and tumor response determined by the RECICL (p = 0.0007). Conclusion: Based on the analysis, using many cases at a single center, we concluded that continuation of treatment with sorafenib for ≥90 days without decrease of liver function was critical if tumor response was determined as stable disease or higher.

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Phase II Study of Gemcitabine and Oxaliplatin in Combination With Bevacizumab in Patients With Advanced Hepatocellular Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.9130 ◽

2006 ◽

Vol 24 (12) ◽

pp. 1898-1903 ◽

Cited By ~ 275

Author(s):

Andrew X. Zhu ◽

Lawrence S. Blaszkowsky ◽

David P. Ryan ◽

Jeffrey W. Clark ◽

Alona Muzikansky ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase Ii ◽

Phase Ii Study ◽

Objective Response ◽

Progression Free Survival ◽

Vascular Tumor ◽

Advanced Hepatocellular Carcinoma ◽

Close Monitoring ◽

Grade 3 ◽

Transient Elevation

Purpose Hepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis. Given the reported activity of gemcitabine and oxaliplatin (GEMOX) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab (B), a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients. Patients and Methods Eligible patients had pathologically proven measurable unresectable or metastatic HCC. For cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone intravenously on day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was administered on days 1 and 15, gemcitabine 1,000 mg/m2 was administered as a dose rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and 16. Results Thirty-three patients were enrolled and 30 patients were assessable for efficacy. The objective response rate was 20%, and 27% of patients had stable disease. Median overall survival was 9.6 months (95% CI, 8.0 months to not available) and median progression-free survival (PFS) was 5.3 months (95% CI, 3.7 to 8.7 months); the PFS rate at 3 and 6 months was 70% (95% CI, 54% to 85%) and 48% (95% CI, 31% to 65%), respectively. The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia, transient elevation of aminotransferases, hypertension, and fatigue. Conclusion GEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC. The high 6-month PFS rate is encouraging, and this regimen is worthy of further investigation.

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Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: A Subgroup Analysis of Asian Patients in the Phase 3 KEYNOTE-240 Trial

Liver Cancer ◽

10.1159/000515553 ◽

2021 ◽

pp. 1-10

Author(s):

Masatoshi Kudo ◽

Ho Yeong Lim ◽

Ann-Lii Cheng ◽

Yee Chao ◽

Thomas Yau ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Progression Free Survival ◽

Best Supportive Care ◽

The Philippines ◽

Advanced Hepatocellular Carcinoma ◽

Asian Patients ◽

Primary Endpoints ◽

Duration Of Response ◽

Grade 3

Introduction: KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. Methods: Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. Results: The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6–4.1) versus 1.4 months (95% CI 1.4–2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32–0.70). The median OS was 13.8 months (95% CI 10.1–16.9) for pembrolizumab versus 8.3 months (95% CI 6.3–11.8) for placebo (HR 0.55; 95% CI 0.37–0.80). ORR was 20.6% (95% CI 13.4–29.5) for pembrolizumab versus 2.0% (95% CI 0.1–10.6) for placebo (difference: 18.5%; 95% CI 8.3–27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3–5 TRAEs, respectively. No treatment-related deaths occurred. Conclusion: Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.

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