Purpose TP53 mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial.
Materials and Methods
We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: Group 1, alpelisib; Group 2, poziotinib; Group 3, nintedanib; and Group 4, abemaciclib. If there was no identifiable target, the patients were allocated to Group 5 (durvalumab ± tremelimumab).
Results TP53 mutations were detected in 116/179 patients (64.8%), more frequently in HPV-negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival (PFS) than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in Group 5 (8.1 vs. 33.0 months, p=0.001).
Conclusion TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.
Kyoo Hyun Kim, Sun Min Lim, Hee Kyung Ahn, Yun-Gyoo Lee, Keun-Wook Lee, Myung-Ju Ahn, Bhumsuk Keam, Hye Ryun Kim, Hyun Woo Lee, Ho Jung An, Jin-Soo Kim
Cancer Res Treat. 2024;56(1):37-47. Published online July 20, 2023
Purpose Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial.
Materials and Methods The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)–based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis.
Results Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable.
Conclusion Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.
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Cancer Res Treat. 2024;56(1):48-60. Published online June 27, 2023
Purpose This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC).
Materials and Methods Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS).
Results In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib.
Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.
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Cancer Res Treat. 2022;54(1):109-117. Published online April 27, 2021
Purpose Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy.
Materials and Methods Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments.
Results Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%).
Conclusion Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients’ preference, morbidity, and prognosis.
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Purpose This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.
Materials and Methods We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.
Results The patients received anti–programmed cell death protein-1 (PD-1) (n=73, 58%), anti–programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti–PD-1/PD-L1 and anti–cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.
Conclusion ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.
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Purpose
This study aimed to investigate the prevalence and risk factors of burnout and occupational stress among medical oncologists in Korea.
Methods
A survey was conducted of medical oncologists who were members of Korean Society for Medical Oncology (KSMO) using the Korean Occupational Stress Scale, the validated Maslach Burnout Inventory (MBI) and supplemental questions about work and lifestyle factors.
Results
Among 220 active KSMO members, 111 responses were collected. The median age was 42 years (range, 32 to 63 years). Two-thirds of responders worked 6 days per week and half of them worked a total of 60-80 hours per week. Each medical oncologist treated a median of 90-120 patients per week in outpatient clinics and 20-30 patients per week in patient practices. MBI subscales indicated a high level of emotional exhaustion in 74%, a high level of depersonalization in 86%, and a low level of personal accomplishment in 65%: 68% had professional burnout according to high emotional exhaustion and high depersonalization scores. The risk of burnout was higher for medical oncologists aged from 30-39 than 40-49 years, and unmarried than married. Considering personal accomplishment, females had a higher risk of burnout. The median score of occupational stress was 63 (range, 43 to 88). Having night-duty call was the strongest risk factor on more stress. A higher stress score was associated with a higher prevalence of burnout.
Conclusion
Burnout and occupational stress are quite common amongst Korean medical oncologists. Achieving a healthy work-life balance, ensuring balanced workload distribution, and engaging in proper stress relief solutions are necessary.
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Cancer Res Treat. 2020;52(3):907-916. Published online March 18, 2020
Purpose
The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting.
Materials and Methods
Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.
Results
A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.
Conclusion
In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.
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Cancer Res Treat. 2019;51(3):1249-1256. Published online January 2, 2019
Purpose
The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy.
Materials and Methods
Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC).
Results
The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006).
Conclusion
KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.
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Purpose
This study was conducted to explore the process and operation of a cancer multidisciplinary team (MDT) after the reimbursement decision in Korea, and to identify ways to overcome the major barriers to effective and sustainable MDTs.
Materials and Methods
Approximately 1,000 cancer specialists, including medical oncologists, surgical oncologists, radiation oncologists, pathologists, and radiologists in general hospitals in Koreawere invited to complete the survey. The questionnaire covered the following topics: organizational structure of MDTs, candidates for consulting, the clinical decision-making initiative, and responsibility for dealing with legal disputes.
Results
We collected a total of 179 responses (18%) from physicians at institutions where an MDT approachwas active. A surgical oncologist (91%), internist (90%),radiologist (89%),radiation oncologist (86%), pathologist (71%), and trainees (20%) regularly participated in MDT operations. Approximately 55% of respondents stated that MDTs met regularly. In cases of a split opinion, the physician in charge (69%) or chairperson (17%) made the final decision, and most (86%) stated they followed the final decision. About 15% and 32% of respondents were “very satisfied” and “satisfied,” respectively, with the current MDT’s operations. Among 38 institutional representatives, 34% responded that the MDT operation became more active and 18% stated an MDT was newly implemented after the reimbursement decision.
Conclusion
The reimbursement decision invigorated MDT operations in almost half of eligible hospitals. Dissatisfaction regarding current MDTs was over 50%, and the high discordance rates regarding risk sharing suggest that it is necessary to revise the current system of MDTs.
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Purpose Cisplatin-associated arterial and venous thromboembolic events (TEEs) are becoming an increasing concern. In patients with small-cell lung cancer (SCLC) who are treated using cisplatin-based chemotherapy, we assume that the overall risk of TEEs is high. However, cisplatin-associated vascular toxicity in patients with SCLC has been overlooked to date. The aim of this study was to determine the incidence of TEEs in patients with SCLC and to analyze the predictors for TEE occurrence. Materials and Methods We retrospectively analyzed 277 patients who received chemotherapy for SCLC between 2006 and 2012. As the influence of chemotherapy on TEE occurrence developed after its initiation, a time-dependent Cox regression analysis was used to estimate the significant predictors for TEE. Results Among the 277 patients, 30 patients (11%) developed a TEE. The 3-month, 6-month, and 1-year cumulative incidences of TEEs were 5.0%, 9.1%, and 10.2%, respectively. Of 30 total TEEs, 22 (73%) occurred between the time of initiation and 4 weeks after the last dose of platinum-based chemotherapy. Approximately 218 patients (79%) received cisplatin-based chemotherapy. In multivariate analysis, cisplatin-based chemotherapy was an independent risk factor for TEE occurrence (hazard ratio [HR], 4.36; p=0.05). Variables including smoking status (common HR, 2.14; p=0.01) and comorbidity index (common HR, 1.60; p=0.05) also showed significant association with TEE occurrence. Conclusion The 1-year cumulative incidence of TEE is 10.2% in Asian patients with SCLC. Cisplatinbased chemotherapy in SCLC might be a strong predictor for the risk of TEE.
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Purpose
We previously reported the prevalence of monoclonal gammopathy of undetermined significance (MGUS) to be 3.3% among an elderly Korean urban cohort recruited during 2005-2006. Here, we report a 5-year follow-up study of the previously identified MGUS cohort.
Materials and Methods
The 680 participants from the initial cohort were followed-up for a median of 5 years. Sera were collected between 2010 and 2011. Two-step screening was performed with standard serum electrophoresis followed by immunofixation and determination of the serum concentration of monoclonal-protein (M-protein).
Results
Of the 680 participants (21 with MGUS), 348 (51%) agreed to participate in the follow-up study and 10 were found to have MGUS. Among the 21 MGUS patients initially identified, nine were followed-up, six had persistent M-protein, and one patient had progressed to multiple myeloma (progression rate, 1.0%/yr). The M-protein disappeared in the remaining two individuals. Among the 339 participants without MGUS who were followed-up, four developed an M-protein. There was no significant difference in survival with respect to the presence of MGUS (p=0.66).
Conclusion
The 5-year follow-up data show that the natural clinical course of MGUS in Korea is similar to that in Western countries. MGUS was not associated with an increased risk of death over the 5-year study period.
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