Evaluating the effect of a mobile-based symptom monitoring system for improving physical function in patients with cancer during chemotherapy: study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Symptoms due to chemotherapy are common in patients with cancer. Cancer-related symptoms are closely associated with the deterioration of physical function which can be associated with decreased quality of life and increased mortality. Thus, timely symptom identification is critical for improving cancer prognosis and survival. Recently, remote symptom monitoring system using digital technology has demonstrated its effects on symptom control or survival. However, few studies examined whether remote monitoring would contribute to retaining physical function among patients with cancer. Therefore, this study aimed to evaluate the effectiveness of mobile-based symptom monitoring in improving physical function among patients with cancer under chemotherapy. METHODS AND ANALYSIS: This study is a multicentre, open-label, parallel-group, randomised controlled trial. We will recruit 372 patients at three tertiary hospitals located in Seoul, South Korea. Study participants will be randomly assigned to either an intervention group receiving the ePRO-CTCAE app and a control group receiving routine clinical practice only. The primary outcome is changes in physical function from commencement to completion of planned chemotherapy. A linear mixed model will be performed under the intention-to-treat principle. The secondary outcomes include physical activity level; changes in pain interference; changes in depressive symptom; unplanned clinical visits; additional medical expenditure for symptom management; completion rate of planned chemotherapy; changes in symptom burden and health-related quality of life; and 1-year overall mortality. ETHICS AND DISSEMINATION: The study has been approved by the institutional review board and ethics committee at the three university hospitals involved in this trial. Written informed consent will be obtained from all the participants. The results of the trial will be submitted for publication in peer-reviewed academic journals and disseminated through relevant literatures. TRIAL REGISTRATION NUMBER: KCT0007220.

Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study.

OBJECTIVES: This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment. MATERIALS AND METHODS: We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab. RESULTS: We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil-lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001). CONCLUSION: Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers.

Lazertinib as a frontline treatment in patients with EGFR-mutated advanced non-small cell lung cancer: Long-term follow-up results from LASER201.

OBJECTIVE: This analysis of the first-line cohort of LASER201 study evaluated the efficacy and safety of lazertinib 240 mg as a frontline therapy for epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: A total of 43 patients, with EGFR mutation-positive (Exon19Del, n = 24; L858R, n = 18; G719X, n = 1) locally advanced or metastatic NSCLC who had not previously received EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, received once-daily lazertinib 240 mg. EGFR mutation status was confirmed by local or central testing. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review. Secondary efficacy endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), tumor shrinkage, and overall survival (OS). RESULTS: At the primary data cut-off (DCO; January 8, 2021), the ORR was 70 % (95 % confidence interval [CI]: 56.0-83.5), DCR was 86 % (95 % CI: 75.7-96.4) and the median DoR was 23.5 (95 % CI: 12.5-not reached) months. The median PFS was 24.6 (95 % CI: 12.2-30.2) months. At the final DCO (March 30, 2023), the median OS was not estimable and the median follow-up duration for OS was 55.2 [95 % CI: 22.8-55.7] months. OS rates at 36 months and 54 months were 66 % (95 % CI: 47.5-79.3 %) and 55 % (95 % CI: 36.6-70.7 %), respectively. The most commonly reported TEAEs were rash (54 %), diarrhea (47 %), pruritus (35 %), and paresthesia (35 %). No drug-related rash or pruritus TEAEs of grade 3 or higher were reported. Diarrhea and paresthesia of grade 3 or higher were reported in 3 (7 %) and 1 (2 %) patients, respectively. CONCLUSION: This analysis demonstrated long-term clinical benefit with lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for lazertinib was tolerable and consistent with that previously reported.

Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset.

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.

Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial.

PURPOSE: A precise oncologic approach for head and neck squamous cell carcinoma (HNSCC) is necessary. We performed a genomic profile-based umbrella trial for the patients with platinum-refractory recurrent and/or metastatic HNSCC. METHODS: In this multicenter, open-label, single-arm phase II trial, we performed targeted next-generation sequencing (NGS). Patients were assigned to each treatment arm on the basis of their matching genomic profiles: arm 1, alpelisib, a PIK3CA inhibitor; arm 2, poziotinib, an epidermal growth factor receptor/HER2 inhibitor; arm 3, nintedanib, an fibroblast growth factor receptor inhibitor; and arm 4, abemaciclib, a CDK4/6 inhibitor. If there was no matching target, patients were allocated to arm 5, duvalumab ± tremelimumab, anti-PD-L1/cytotoxic T-cell lymphocyte-4 inhibitor. When progressive disease (PD) occurred in arms 1-4, cross over to arm 5 was allowed. The primary end point was disease control rate (DCR) in arm 1 and overall response rate (ORR) in arms 2-5 by investigator assessment. RESULTS: Between October 2017 and August 2020, 203 patients were enrolled, including crossover. In arm 1, the ORR was 21.2% and DCR was 65.6%. The ORR was 0% for arm 2, 42.9% for arm 3, 0% for arm 4, and 15.6% for arm 5. In the case of PD with durvalumab, tremelimumab was added, and the ORR for durvalumab + tremelimumab was 2.2%. The median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months for each arm, respectively. The median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months, respectively. Overall, the toxicity profiles were manageable, and there were no treatment-related deaths. CONCLUSION: To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that NGS-based genomic phenotyping was methodologically feasible and applicable.

A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial.

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.

Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04).

PURPOSE: In the treatment of non-small-cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-mutated NSCLC that progressed before TKI therapy. MATERIALS AND METHODS: We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). RESULTS: A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm. CONCLUSION: To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK-mutated NSCLC who have progressed on relevant targeted therapy.

Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis.

INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases. METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response. RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population. CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.

Lazertinib Versus Gefitinib Tyrosine Kinase Inhibitors in Treatment-Naíve Patients With EGFR-Mutated Advanced NSCLC: Analysis of the Asian Subpopulation in LASER301.

INTRODUCTION: Lazertinib is a third-generation central nervous system-penetrant tyrosine kinase inhibitor targeting mutant EGFR in NSCLC. Lazertinib exhibited improved efficacy versus gefitinib in the LASER301 study; this subset analysis compared lazertinib with gefitinib among Asian patients. METHODS: The phase 3 LASER301 study evaluated lazertinib efficacy and safety in treatment-naive patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC. Patients were randomized one-to-one and received either lazertinib or gefitinib. The primary end point was investigator-assessed progression-free survival using Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included overall survival, objective response rate, duration of response, and safety. RESULTS: Between February 13, 2020, and July 29, 2022, among 258 patients of Asian descent, the median progression-free survival was significantly longer with lazertinib than gefitinib (20.6 versus 9.7 mo; hazard ratio: 0.46; 95% confidence interval [CI]: 0.34-0.63, p < 0.001), and the benefit was consistent across predefined subgroups (exon 19 deletion, L858R, baseline central nervous system metastases). Objective response rate and disease control rates were similar between treatment groups. The median duration of response was 19.4 months (95% CI: 16.6-24.9) versus 9.6 months (95% CI: 6.9-12.4) in the lazertinib versus gefitinib group. Adverse event rates in Asian patients were comparable with the overall LASER301 population. Adverse events leading to discontinuation in the lazertinib and gefitinib groups were 13% and 12%, respectively. CONCLUSIONS: In LASER301, efficacy and safety results in Asian patients were consistent with the overall population. Lazertinib exhibited better efficacy than gefitinib in Asian patients with a tolerable safety profile.

Predicting tolerability of high-dose fentanyl buccal tablets in cancer patients.

BACKGROUND & AIMS: Fentanyl buccal tablets (FBTs) are a rapid-onset opioid indicated for breakthrough cancer pain (BTcP) and FBT titration is needed to optimize BTcP management. We aimed to predict which patients could tolerate a high dose of FBT (400 µg or more at a time). METHODS: A retrospective analysis was performed to assess the final FBT dose. The final FBT doses were compared according to the clinical features. The prediction accuracy of patients tolerant of 400 µg or higher FBT was compared using the area under the receiver operating characteristic (ROC) curves. A risk scoring model based on the odds ratio (OR) was developed from the final multivariable model, and patients were assigned into two groups: low tolerance (0-1 point) and high tolerance (2-3 points). RESULTS: Among 131 patients, the most frequently effective dose of FBT was 200 µg (54%), followed by 100 µg (30%). The median value of morphine equivalent daily doses (MEDD) was 60 mg/day, and the most common daily use was 3-4 times/day. In multivariable analysis, male sex, younger age, and use of FBTs three or more times per day were independently associated with high-dose FBT. According to the risk scoring model, the patients with a final FBT of 400 µg or higher were significantly more in the high tolerance group (17%) compared to the low tolerance group (3%; p = 0.023). CONCLUSIONS: According to the dose relationship between the final FBT dose and the clinical features, three factors (sex, age, daily use of FBT) were independently associated with the final dose of FBT. Our risk score model could help predict tolerance to high-dose FBT and guide the titration plan for BTcP.

Comparison of Treatment Patterns and Clinical Outcomes by Gender in Locally Advanced Head and Neck Squamous Cell Carcinoma (KCSG HN13-01).

We aimed to compare treatment modalities and outcomes by gender in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We characterized the sex-specific differences and compared the overall survival (OS) between male and female patients in a multicenter cohort of LA-HNSCC. To minimize the observed confounding, propensity score matching was utilized. The study included 445 patients; 385 (86.5%) were men and 60 (13.5%) were women. In terms of age, smoking habits, drinking habits, and primary tumor locations, there was a significant imbalance in sex before the matching. Propensity score matching yielded 60 patient pairs, with no statistical difference between the sexes in terms of their characteristics. As for the treatment strategies, there were no significant differences between the sexes before (p = 0.260) and after (p = 0.585) the propensity score matching. When comparing the survival probabilities between the sexes, OS was not significantly different in the overall (HR 1.02; 95% CI 0.59-1.76; p = 0.938) and propensity-score-matched population (HR 1.46; 95% CI 0.68-3.17; p = 0.331). These results suggest that there was no difference in prognosis by gender in the treatment modalities and outcomes of LA-HNSCC in real-world practice.

Clinical outcomes and prognostic factors of cone-beam CT-guided radiofrequency ablation for pulmonary metastases in colorectal cancer patients.

AIM: Radiofrequency ablation (RFA) has been increasingly used for the treatment of pulmonary metastases in various malignancies. METHODS: A retrospective analysis was performed to establish the safety and efficacy of cone-beam computed tomography (CBCT)-guided RFA in patients with metastatic colorectal cancer between 2016 and 2019, and the prognostic factors of local tumor control were assessed. RESULTS: A total of 31 patients with colorectal cancer underwent 48 sessions of lung RFA. The mean diameter of metastases targeted for RFA was 11 mm (range: 4-32), and the RFA was technically successful in 43 sessions (90%). There were 14 complications (29%), the majority of which required no intervention, with no cases of mortality. The median follow-up duration from RFA in the surviving 29 patients was 18.0 months. Only two patients (6%) died of disease progression, and the 3-year overall survival rate was 91% (95% CI: 83-99). Local tumor progression (LTP) of the RFA site was observed in 27%, and the LTP-free survival rates at 1 and 2 years were 81% (95% CI: 70-82) and 64% (95% CI: 50-77), respectively. Multivariate analysis showed that the progression of extra-RFA sites and the presence of extrapulmonary metastasis were independent prognostic factors significantly associated with LTP at RFA site. CONCLUSION: Lung RFA using CBCT guidance is a comparatively safe and effective option for the treatment of lung metastases from colorectal cancer. However, the control of extrapulmonary metastases should be accompanied by combined or sequential systemic treatment and local treatment.

Totality outcome of afatinib sequential treatment in patients with EGFR mutation-positive non-small cell lung cancer in South Korea (TOAST): Korean Cancer Study Group (KCSG) LU-19-22.

Background: Irrespective of the first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor chosen, acquired resistance to therapy is inevitable. Therefore, a key consideration when assessing therapeutic choices is the availability of subsequent treatment options following disease progression. We assessed clinical outcomes in patients who received first-line afatinib treatment with various second-line treatments including osimertinib for patients acquiring the T790M mutation. Methods: A total of 737 EGFR mutation-positive (EGFR M+) non-small cell lung cancer (NSCLC) patients receiving first-line afatinib treatment were categorized by second-line treatment: T790M+ sequentially treated with osimertinib (cohort A, n=116); T790M- given chemotherapy or others (cohort B, n=143); patients with unknown T790M status (cohort C, n=111); and patients who were undergoing afatinib treatment at the time of data collection, were dead, had discontinued afatinib treatment due to serious adverse events or were lost to follow-up (cohort D, n=367). The primary outcomes were total time on treatment (TOT) and TOT for first-line (TOT-1) and second-line treatments (TOT-2). Secondary outcomes were objective response rates (ORR), overall survival (OS), and central nervous system (CNS) efficacy. Results: Median total TOT in cohorts A, B, C, and D were 35.10 months [95% confidence interval (CI): 30.09-43.53 months], 18.80 months (95% CI: 16.92-20.20 months), 12.00 months (95% CI: 10.22-14.98 months), and 42.60 months (95% CI: 30.95-59.23 months), respectively. The ORR of patients given afatinib was 75.7%. In patients with initial brain metastasis without local treatment, the CNS response rate was 67.0% and CNS progression-free survival was 24.70 months (95% CI: 19.84-33.15 months). Conclusions: This study showed that sequential approach of afatinib followed by second line treatment is an effective therapeutic strategy for EGFR M+ NSCLC patients.

COMPrehensive geriatric AsseSSment and multidisciplinary team intervention for hospitalised older adults (COMPASS): a protocol of pragmatic trials within a cohort.

INTRODUCTION: There is an increased demand for services for hospitalised older patients with acute medical conditions due to rapidly ageing population. The COMPrehensive geriatric AsseSSment and multidisciplinary team intervention for hospitalised older adults (COMPASS) study will test the effectiveness of comprehensive geriatric assessment (CGA) and multidisciplinary intervention by comparing it with conventional care among acute hospitalised older adults in Korea. METHODS AND ANALYSIS: A multicentre trial within a cohort comprising three substudies (randomised controlled trials) will be conducted. The intervention includes CGA and CGA-based multidisciplinary interventions by physicians (geriatricians, oncologists), nurses, nutritionists and pharmacists. The multidisciplinary intervention includes nutritional support, medication review and adjustment, rehabilitation, early discharge planning and prevention of geriatric syndromes (falls, delirium, pressure sore and urinary retention). The analysis will be based on an intention-to-treat principle. The primary outcome is living at home 3 months after discharge. In addition to assessing the economic effects of the intervention, a cost-utility analysis will be conducted. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the ethics committees of Seoul National University Bundang Hospital and each study site. The study findings will be published in peer-reviewed journals. Subgroup and further in-depth analyses will subsequently be published. TRIAL REGISTRATION NUMBER: KCT0006270.

The risk of cardiovascular disease and stroke in survivors of head and neck cancer in Korea.

BACKGROUND: Head and neck cancer (HNCA) survivors have a high risk of developing cardiovascular disease (CVD) or stroke because of sharing risk factors of disease. Therefore, we investigated the risk of CVD or stroke occurrence among HNCA survivors in Korea based on the Health Insurance Review and Assessment (HIRA) Service claims database. METHODS: We retrieved claims data of patients who were diagnosed with HNCA in 2014-2015 using ICD-10 code and followed up data until 2018. Patients with newly diagnosed with CVD or stroke after HNCA diagnosis during the follow-up period were detected. We analyzed the characteristics of patients with HNCA who were subsequently diagnosed with CVD or stroke. In addition, the risk factors of CVD or stroke occurrence were investigated using Cox proportional hazard regression analysis. RESULTS: Among the 8288 patients with HNCA, 477 and 404 patients were diagnosed with new-onset CVD and stroke, respectively. Patients with hypertension, diabetes mellitus (DM), and hyperlipidemia had a 3.25-fold higher risk of CVD comparing to patients without any underlying disease (95% confidence index [CI], 2.38-4.45) Patients with three underlying diseases had a 2.92-fold higher risk of stroke compared to patients without any underlying disease (95% CI 2.03-4.21). CONCLUSIONS: HNCA survivors with hypertension, DM, and hyperlipidemia should be cautious of the risks of CVD and stroke.

Evaluation of molecular methods for plasma detection of EGFR mutations in non-small cell lung cancer.

AIM: Epidermal growth factor receptor (EGFR) mutations are detected in non-small cell lung cancer (NSCLC) and associated with responses to therapy with tyrosine kinase inhibitors (TKIs). We compared the analytical performances of two real-time PCRs and droplet digital PCR (ddPCR) to detect EGFR mutations using plasma. METHODS: Plasma EGFR tests were performed using 86 plasma samples from 75 prospectively enrolled NSCLC patients with early and advanced stages. Analytical performances of plasma-using two real-time PCR, Cobas EGFR mutation v2 and PANAMutyper, EGFR kit, and ddPCR were evaluated based on the tissue EGFR test results. The frequencies of EGFR mutations and acquired T790M mutation after TKI therapy were also assessed. RESULTS: The incidence of all EGFR mutations was 52.3% (23/44) in tissue and was up to 43.2% (19/44) in plasma. The Cobas detection rates of three EGFR mutations (exon 19 deletions, L858R, and T790M) in plasma were similar to those in tissue. The Cobas showed a higher detection rate (76.7%) than that by the PANAMutyper (60.5%). Sensitivity for T790M mutation was lower than the sensitivity for the exon 19 deletions or L858R in both tests. Mutant allele frequency measured by ddPCR was significantly correlated with the semi-quantitative values of the Cobas. CONCLUSIONS: Plasma EGFR tests showed similar detection rates for common EGFR mutations compared to the tissue EGFR tests. Cobas showed higher sensitivity in detection of EGFR mutations in body fluids than the PANAMutyper. Real-time PCR using plasma or body fluids could be a suitable first test for the detection of EGFR mutations.

Long-term outcomes in patients with advanced and/or metastatic non-small cell lung cancer who completed 2 years of immune checkpoint inhibitors or achieved a durable response after discontinuation without disease progression: Multicenter, real-world data (KCSG LU20-11).

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown significant improvements in patients with advanced non-small cell lung cancer (NSCLC). One of the major issues with ICIs is determining the optimal treatment duration. METHODS: This multicenter, retrospective study analyzed clinical outcomes in patients with NSCLC who completed 2 years of ICI therapy or were treated for more than 6 months and then discontinued ICIs without disease progression at 11 medical centers in Korea between August 2017 and December 2020. RESULTS: Ninety-six patients who completed 2 years of ICIs were reviewed. The median durations of treatment and follow-up were 24.0 and 33.9 months, respectively. The objective response rate (ORR) was 85.4%. The median progression-free survival (PFS) and overall survival (OS) periods were not reached. After completion, the PFS and OS rates were 81.1% and 96.4%, respectively, at 12 months. Forty-three patients were identified who discontinued ICIs without disease progression: 26 (60.5%) for adverse events and 17 (39.5%) for other causes. The median durations of treatment and follow-up were 10.5 and 21.2 months, respectively. The ORR was 90.7%. The median PFS and OS periods were not reached. After discontinuation, the PFS and OS rates were 71.0% and 90.0%, respectively, at 12 months. CONCLUSIONS: A significantly high proportion of patients who completed 2 years of ICI therapy continued to experience long-term PFS. Even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long-term survival. LAY SUMMARY: The optimal treatment duration for immune checkpoint inhibitors (ICIs) remains to be determined. This study reports the long-term outcomes of patients with non-small cell lung cancer who completed 2 years of ICI therapy or achieved a durable response after the discontinuation of ICIs without disease progression in real-world practice. A significantly high proportion of patients who completed 2 years of ICIs continued to experience long-term progression-free survival. In addition, even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long-term survival.

Induction Chemotherapy as a Prognostication Index and Guidance for Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: The Concept of Chemo-Selection (KCSG HN13-01).

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.

Characteristics and treatment patterns in older patients with locally advanced head and neck cancer (KCSG HN13-01).

BACKGROUND/AIMS: Treatment decisions for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are complicated, and multi-modal treatments are usually indicated. However, it is challenging for older patients to complete treatments. Thus, we investigated disease characteristics, real-world treatment, and outcomes in older LA-HNSCC patients. METHODS: Older patients (aged ≥ 70 years) were selected from a large nationwide cohort that included 445 patients with stage III-IVB LA-HNSCC from January 2005 to December 2015. Their data were retrospectively analyzed and compared with those of younger patients. RESULTS: Older patients accounted for 18.7% (83/445) of all patients with median age was 73 years (range, 70 to 89). Proportions of primary tumors in the hypopharynx and larynx were higher in older patients and older patients had a more advanced T stage and worse performance status. Regarding treatment strategies of older patients, 44.5% of patients received concurrent chemoradiotherapy (CCRT), 41.0% underwent surgery, and 14.5% did not complete the planned treatment. Induction chemotherapy (IC) was administered to 27.7% (23/83) of older patients; the preferred regimen for IC was fluorouracil and cisplatin (47.9%). For CCRT, weekly cisplatin was prescribed 3.3 times more often than 3-weekly cisplatin (62.2% vs. 18.9%). Older patients had a 60% higher risk of death than younger patients (hazard ratio, 1.6; p = 0.035). Oral cavity cancer patients had the worst survival probability. CONCLUSION: Older LA-HNSCC patients had aggressive tumor characteristics and received less intensive treatment, resulting in poor survival. Further research focusing on the older population is necessary.

A Phase 1/2 Study of Lazertinib 240 mg in Patients With Advanced EGFR T790M-Positive NSCLC After Previous EGFR Tyrosine Kinase Inhibitors.

INTRODUCTION: This integrated analysis of a phase 1/2 study (NCT03046992) evaluated the efficacy and safety of lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), in patients with advanced EGFR T790M-positive NSCLC after previous EGFR TKI therapy. METHODS: Adults with EGFR mutation-positive NSCLC that progressed after prior EGFR-directed TKIs received once daily oral lazertinib 240 mg continuously until disease progression. Prior TKIs to treat T790M-positive NSCLC were prohibited. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included progression-free survival, overall survival, and intracranial ORR. RESULTS: A total of 78 patients received lazertinib 240 mg at 17 centers in South Korea. Among patients with T790M-positive tumors at baseline (N = 76), one (1.3%) had a complete response and 41 (53.9%) had partial responses, giving an ORR of 55.3% (95% confidence interval [CI]: 44.1-66.4). Median progression-free survival was 11.1 months (95% CI: 5.5-16.4). Median overall survival was not reached (median follow-up = 22.0 mo). In patients with measurable intracranial lesions (n = 7), one (14.3%) had a complete intracranial response and five (71.4%) had partial responses, giving an intracranial ORR of 85.7% (95% CI: 59.8%-100.0%). The most common treatment-emergent adverse events were rash (37.2%), pruritus (34.6%), and paresthesia (33.3%); most were mild to moderate in severity. Serious drug-related adverse events occurred in three patients (gastritis, pneumonia, pneumonitis). The major mechanism of resistance was EGFR T790M loss. CONCLUSIONS: Lazertinib 240 mg/d has a manageable safety profile with durable antitumor efficacy, including brain metastases, in patients with advanced T790M-positive NSCLC after previous EGFR TKI therapy.