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Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.
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Palbociclib combined with endocrine therapy is approved for treating patients with hormone-receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer; however, data on palbociclib combined with tamoxifen are limited. We investigated the efficacy and safety of palbociclib-tamoxifen in patients with HR+/HER2- advanced breast cancer. This double-blind phase 3 study included 184 women who were randomly assigned 1:1 to receive palbociclib-tamoxifen or placebo-tamoxifen. Pre/perimenopausal women also received goserelin. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Median PFS was 24.4 months (95% confidence interval [CI], 13.1-32.4) with palbociclib-tamoxifen and 11.1 months (95% CI, 7.4-14.6) with placebo-tamoxifen (hazard ratio [HR], 0.60; 95% CI, 0.43-0.85; P = 0.002). Palbociclib-tamoxifen improved PFS in patients who were treated with first-line or second-line endocrine therapy and pre-, peri-, and postmenopausal patients. Though OS data are still immature (median not reached in both groups), an overall risk reduction of 27% (HR, 0.73; 95% CI, 0.44-1.21) with palbociclib-tamoxifen was observed at the time of PFS analysis. The most common grade 3/4 adverse event with palbociclib-tamoxifen was neutropenia (89.0% [none were febrile] versus 1.1% with placebo-tamoxifen). There were no deaths owing to adverse events in either group. Among patients with HR+/HER2- advanced breast cancer, palbociclib-tamoxifen resulted in significantly longer PFS than tamoxifen alone. Early OS data showed a trend favoring palbociclib-tamoxifen. Trial registration: ClinicalTrials.gov number, NCT03423199. Study registration date: February 06, 2018.
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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III PRODIGY study demonstrated that neoadjuvant chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 chemotherapy (CSC) improved progression-free survival (PFS) compared with surgery followed by adjuvant S-1 (SC) for patients with resectable locally advanced gastric cancer (LAGC) with clinical T2-3N+ or T4Nany disease. The primary end point was PFS. Overall survival (OS) was the secondary end point. We herein report the long-term follow-up outcomes, including OS, from this trial. A total of 238 and 246 patients were randomly assigned to the CSC and SC arms, respectively, and were treated (full analysis set). As of the data cutoff (September 2022), the median follow-up duration of the surviving patients was 99.5 months. Compared with SC, CSC significantly increased the OS (adjusted hazard ratio [HR], 0.72; stratified log-rank P = .027) with an 8-year OS rate of 63.0% and 55.1% for the CSC and SC arms, respectively. CSC also significantly improved the PFS (HR, 0.70; stratified log-rank P = .016). In conclusion, neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with LAGC relative to patients treated with surgery and adjuvant S-1. It should be considered one of the standard treatment options for patients with LAGC in Asia.
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The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.
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Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama , Femenino , Humanos , Adyuvantes Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Docetaxel/uso terapéutico , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Receptor ErbB-2/uso terapéutico , Trastuzumab/uso terapéuticoRESUMEN
BACKGROUND: Both first and second-generation EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data on the difference in efficacy of EGFR-TKIs based on the type of EGFR mutation and agents. METHODS: This retrospective real-world study evaluated the outcomes and clinicopathologic characteristics, including the type of EGFR mutations, of 237 advanced NSCLC patients treated with first- or second-generation (afatinib) EGFR-TKIs as first-line therapy. RESULTS: The median progression-free survival (PFS) and overall survival (OS) of all patients were 11 months (M) and 25M, respectively. In the univariate analysis, patients with exon 19 deletion (del) (n=130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p=0.047), without a difference in PFS (p=0.138). Patients treated with afatinib (n=60) showed significantly longer median OS compared to those treated with first-generation TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p=0.037), without a difference in PFS (p=0.179). In patients with exon 19 del, there was no significant difference in median PFS (p=0.868) or OS (p=0.361) between patients treated with afatinib and those treated with first-generation TKIs, while significantly better PFS (p=0.042) and trend in OS (p=0.069) were observed in patients receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p=0.028), while age >70 years (p=0.017), ECOG performance status ≥2 (p=0.001), primary metastatic disease (p=0.007), and synchronous brain metastasis (p=0.026) were independent prognostic factors of poor OS. CONCLUSIONS: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC patients receiving first-line EGFR-TKIs. Moreover, in patients with exon 19 del, first-generation TKIs seem to be a reasonable treatment option if osimertinib is unavailable.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Afatinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores ErbB/genética , MutaciónRESUMEN
BACKGROUND/AIM: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents. PATIENTS AND METHODS: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors. RESULTS: As first-line therapy, most of the patients (83.5%) received FOLFOX plus bevacizumab (35.4%), followed by FOLFIRI plus bevacizumab (18.8%), FOLFIRI plus cetuximab (17.0%), and FOLFOX plus cetuximab (12.3%). Bevacizumab was the most frequent agent (78.8%) combined with chemotherapy in RAS-mutated CRC, while cetuximab (57.2%) in RAS wild-type CRC. Cetuximab was frequently combined with a doublet regimen in patients with left-sided CRC than in those with right-sided CRC (34.4% vs. 16%). As second-line therapy, most patients (63.4%) also received doublet regimens with bevacizumab, and FOLFIRI plus aflibercept was administered in 15.1%. The objective response rate with FOLFIRI plus cetuximab was significantly higher in patients with left-sided CRC than in those with right-sided CRC (59.2% vs. 30.8%, p=0.008) and marginally higher in patients with RAS wild-type CRC than in those with RAS-mutated CRC (55.6% vs. 0.0%, p=0.092). Progression-free survival (PFS) with FOLFOX plus bevacizumab was significantly shorter than that with FOLFIRI plus bevacizumab (p=0.030) in RAS-mutated CRC, whereas there were no significant differences between regimens in RAS wild-type CRC. CONCLUSION: In patients with unresectable metastatic colorectal cancer, doublet chemotherapy with targeting agents is the most common therapy and efficacy depends on the mutation status as well as clinical factors.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Cetuximab , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Pronóstico , Neoplasias del Recto/tratamiento farmacológicoRESUMEN
BACKGROUND: Thromboembolic events (TEEs) are significant adverse events that can cause serious morbidities and mortality in cancer patients receiving chemotherapy. Patients with gastric cancer (GC) treated with palliative chemotherapy have been reported to experience a TEE incidence of 5-27%. However, very few reports have addressed TEEs in adjuvant chemotherapy (AC) for GC. METHODS: This study retrospectively analyzed 611 GC patients (stage II: 309, III: 302) who started AC with capecitabine/oxaliplatin (167 patients) or S-1 (444 patients) after undergoing curative resection between January 2013 and June 2020 at a single center. The incidence of TEEs during AC or within 1 year after AC completion was investigated, while analyzing the factors that influenced the TEEs' occurrence. RESULTS: TEEs were confirmed in 20 patients (3.3%), and TEEs occurred in almost all patients in the S-1 group (19 patients). The most common TEE types were cerebral infarction and pulmonary thromboembolism (five patients each). Although old age (≥ 70 years, p < 0.0001), S-1 treatment (p = 0.021), and hypertension (p = 0.017) were identified as significant risk factors for TEEs in univariate analysis, only old age showed a statistically significant correlation with TEEs' occurrence in multivariate analysis (odds ratio: 3.07; 95% confidence interval 1.11-8.48; p = 0.031). CONCLUSIONS: TEEs occurred in fewer patients with GC who had been treated with AC than patients who had received palliative chemotherapy in previous reports. However, elderly GC patients who are undergoing AC require more careful surveillance for possible TEEs, considering relatively higher incidence of them.
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Neoplasias Gástricas , Tromboembolia , Humanos , Anciano , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/complicaciones , Tromboembolia/inducido químicamente , Tromboembolia/epidemiología , Quimioterapia Adyuvante/efectos adversos , Oxaliplatino/uso terapéuticoRESUMEN
BACKGROUND: One-year S-1 or six-month capecitabine/oxaliplatin (CAPOX) has been the standard adjuvant chemotherapy for gastric cancer (GC). We investigated outcomes according to the cycles of adjuvant chemotherapy, using data from the Korean Health Insurance and Assessment Service. METHODS: A total of 20,552 patients, including 13,614 patients who received S-1 and 6,938 patients who received CAPOX extracted from 558,442 patients were retrospectively analyzed. The five-year overall survival rate was evaluated according to the duration of adjuvant chemotherapy. RESULTS: The five-year overall survival rate gradually increased according to the increase in adjuvant chemotherapy cycles in both the S-1 (≤ 5 cycles: 48.4%, hazard ratio [HR] 4.06, 95% confidence interval [CI] 3.74-4.40, P < 0.0001; 5 < cycles ≤ 6: 55.4%, HR 3.08, 95% CI 2.65-3.57, P < 0.0001; 6 < cycles ≤ 7: 64.1%, HR 2.11, 95% CI 1.84-2.41, P < 0.0001; 7 < cycles < 8: 71.1%, HR 1.60, 95% CI 1.39-1.84, P < 0.0001; ≥ 8 cycles: 77.9%) and the CAPOX groups (≤ 4 cycles: 43.5%, HR 3.20, 95% CI 2.84-3.61, P < 0.0001; 5 cycles: 45.3%, HR 2.63, 95% CI 2.11-3.27, P < 0.0001; 6 cycles: 47.1%, HR 2.09, 95% CI 1.76-2.49, P < 0.0001; 7 cycles: 55.3%, HR 1.63, 95% CI 1.35-1.96, P < 0.0001; ≥ 8 cycles: 67.2%). CONCLUSIONS: Reducing the treatment cycles of adjuvant chemotherapy in GC with S-1 or CAPOX showed inferior survival outcomes. Completing the standard duration of adjuvant chemotherapy with S-1 or CAPOX would be strongly recommended.
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Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Quimioterapia Adyuvante , Estudios de Cohortes , Supervivencia sin Enfermedad , Fluorouracilo , Humanos , Estadificación de Neoplasias , Compuestos Organoplatinos , Oxaliplatino , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
PURPOSE: The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS: This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS: In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION: This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481).
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Neoplasias del Colon , Compuestos Organoplatinos , Oxaliplatino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Estadificación de Neoplasias , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino/uso terapéuticoRESUMEN
Thromboembolic events (TEEs) are common in cancer patients, with increased risk of TEE by chemotherapy in patients with lung cancer. However, TEEs in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy have rarely been reported. This study retrospectively analyzed real-world data of 275 patients with NSCLC treated with adjuvant chemotherapy after surgery from October, 2005 to June, 2020, in a single institution. The incidence of TEEs during or within one year of completion of adjuvant chemotherapy was investigated, and factors related to TEEs were analyzed. TEEs were confirmed in nine patients (3.3%), without fatal event related to TEEs. None of the factors, including Khorana score, was significantly associated with the occurrence of TEEs. All patients with TEEs had pathologic stage IIB or higher and a history of smoking, except for one patient. In conclusion, TEEs occurred in a smaller proportion of patients with NSCLC treated with adjuvant chemotherapy in the real world compared with those treated with palliative chemotherapy in previous reports. Furthermore, prophylactic anticoagulation in patients with NSCLC receiving adjuvant chemotherapy may not be needed except for high-risk patients, although those patients should be informed about the possible risk of TEEs.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Tromboembolia , Adyuvantes Inmunológicos/uso terapéutico , Adyuvantes Farmacéuticos/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quimioterapia Adyuvante/efectos adversos , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/epidemiología , Estadificación de Neoplasias , Estudios Retrospectivos , Tromboembolia/tratamiento farmacológico , Tromboembolia/epidemiología , Tromboembolia/etiologíaRESUMEN
BACKGROUND/AIMS: The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence. METHODS: Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. RESULTS: TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). CONCLUSION: The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.
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Cisplatino , Neoplasias de Cabeza y Cuello , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia/efectos adversos , Cisplatino/efectos adversos , Neoplasias de Cabeza y Cuello/terapia , Humanos , IncidenciaRESUMEN
BACKGROUND/AIMS: The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains to be determined. METHODS: A retrospective review was conducted on 77 NSCLC patients with synchronous BM who underwent first-line EGFR-tyrosine kinase inhibitor (TKI) Tx. The outcomes of patients were analyzed according to the clinicopathological characteristics including local Tx modalities. RESULTS: Fifty-nine patients underwent local Tx for BM (gamma knife surgery [GKS], 37; whole brain radiotherapy [WBRT], 18; others, four) concurrently or sequentially with EGFR-TKI. Patients treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all patients were 9 and 19 months, respectively. In 60 patients with follow-up brain imaging, the median time to CNS progression was 15 months. Patients with EGFR exon 19 deletion had a significantly longer median OS than those with other mutations including L858R (23 months vs. 17 months). Other clinical characteristics, including CNS symptoms, number of BM, and the use of local Tx were not associated with OS, as well as PFS. In terms of the local optimal Tx modality, no difference was found between GKS and WBRT in the OS and PFS. CONCLUSION: This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC patients with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Patients with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: Palbociclib plus endocrine therapy (ET) demonstrated significant progression-free survival (PFS) benefit in Young Pearl, a randomized phase ll trial comparing palbociclib + ET versus capecitabine in premenopausal women with hormone receptor positive, HER2 negative metastatic breast cancer (MBC). This exploratory analysis investigated potential biomarkers of palbociclib plus ET on PFS. PATIENTS AND METHODS: Of 178 patients randomized (92 palbociclib plus ET; 86 capecitabine), we performed targeted sequencing (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response on PFS. Hazard ratios (HRs) were estimated using unstratified Cox proportional hazards models. RESULTS: PIK3CA (41%) and TP53 (33%) mutations and CCND1 copy number variation (29%) were found most frequently in targeted sequencing of 141 patients. ESR1 mutations were found only in 3.5% of patients of this population. Luminal type showed better prognosis in palbociclib + ET arm but no impact on PFS difference in capecitabine arm. High TMB, TP53 mutation, PTEN loss of function mutation and RB1 pathway alteration showed worse prognosis in palbociclib plus ET arm. Patients with BRCA2 pathogenic mutations showed worse prognosis regardless of PAM50 subtypes. AURKA mutation/amplification, BRIP1/MYC/RAD51C amplification were significantly associated to the patients with short PFS <6 month. CONCLUSION: Of palbociclib plus ET, luminal type showed better prognosis and BRCA2 pathogenic mutation showed worse prognosis regardless luminal/non-luminal type. Further exploration of molecular variables is warranted to determine and validate biomarkers of efficacy and resistance.
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Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Variaciones en el Número de Copia de ADN , Femenino , Hormonas/uso terapéutico , Humanos , Piperazinas , Piridinas , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismoRESUMEN
BACKGROUND: Standard intravenous (IV) paclitaxel is associated with hypersensitivity/toxicity. Alternative IV formulations have improved tolerability but still require frequent hospital visits and IV infusion. DHP107 is a novel oral formulation of paclitaxel that is approved in South Korea for the treatment of gastric cancer. METHODS: This multicenter, phase II study using a Simon's two-stage design investigated the efficacy and safety of DHP107 200 mg/m2 administered orally twice daily on days 1, 8, and 15 every 4 weeks for the first-line treatment of recurrent or metastatic HER2-negative breast cancer. RESULTS: Thirty-six patients were enrolled and 31 were assessable for efficacy. Patient median age was 57 years (range = 34-81) and 11 (31%) had triple-negative disease. A median of seven cycles (range = 1-28) of DHP107 was administered. Objective response rate was 55% (17 patients), all partial responses, according to the investigator's decision and independent central review (ICR), and 44% (4/9 patients) in those with triple-negative disease. Disease control rate (partial response and stable disease) was 74% (23 patients) according to the investigator's decision and ICR. In the intention-to-treat (ITT) population of all enrolled participants, the objective response rate was 50% (18/36 patients). Median progression-free survival was 8.9 months [95% confidence interval [CI]: 5.2-12.3) and median time to treatment failure was 8.0 months (95% CI: 4.2-10.0). DHP107 had an acceptable toxicity profile. All patients experienced treatment-emergent adverse events; the most common adverse events were decreased neutrophil count (81% all grades and 78% grade ⩾ 3) followed by peripheral sensory neuropathy (61% all grades and 8% grade 3). However, there was no febrile neutropenia or sepsis. CONCLUSION: DHP107 showed promising efficacy and acceptable tolerability in this phase II study and is currently being investigated in the OPTIMAL phase III study (NCT03315364). TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov identifier: NCT03315364.
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Central venous catheters (CVCs) are generally required for chemotherapy in patients with acute leukemia, but catheter-related infection is one of the common causes of neutropenic fever. We investigated the in-hospital mortality according to early removal of CVCs and the factors influencing the mortality in patients with acute leukemia undergoing remission induction chemotherapy. This study retrospectively analyzed the hospital record data of 278 patients with acute leukemia treated with non-tunneled CVCs and remission induction chemotherapy in a single institution. Bloodstream infection was more common (p < 0.0001) and median peak C-reactive protein (CRP) levels after neutropenic fever were significantly higher (23.3 vs. 14.5 mg/dl, p = 0.003) in the group with early removal than in the group with maintenance of the CVC. Multivariate analysis of the patients revealed a significant decrease in the mortality with female gender (odds ratio (OR): 0.19, 95% confidence interval (CI): 0.06-0.54, p = 0.002) and a significant increase in the mortality according to the peak CRP (OR 1.12, 95% CI: 1.07-1.17, p < 0.0001). By contrast, early removal of the CVC had no significant effect on the mortality (OR = 1.16, 95% CI: 0.54-2.47, p = 0.706) in univariate analysis. Furthermore, subsequent bloodstream infection after clinical decision for maintenance or early removal of the CVC was confirmed more frequently in the group with early removal (early removal, 22.6%; maintenance, 7.6%, p < 0.0001). Early removal of the CVC had no benefit regarding the mortality and prophylaxis of bloodstream infection in patients with acute leukemia undergoing remission induction chemotherapy. Therefore, maintaining a CVC for as long as possible may be considered, if catheter-related bloodstream infection is not strongly suspected.
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Infecciones Relacionadas con Catéteres/prevención & control , Catéteres Venosos Centrales/efectos adversos , Remoción de Dispositivos , Mortalidad Hospitalaria , Leucemia Mieloide Aguda/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Adulto , Factores de Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bacteriemia/epidemiología , Bacteriemia/etiología , Bacteriemia/prevención & control , Infecciones Relacionadas con Catéteres/etiología , Neutropenia Febril/etiología , Femenino , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: Evaluation of symptoms and signs for the management of neuropathic cancer pain (NCP) is challenging. This study aimed to identify clinical predictors of NCP and symptoms and signs most relevant of those in Korean patients. METHODS: This nationwide, descriptive, cross-sectional, multicenter, observational study included 2,003 cancer patients aged ≥20 years who reported a visual analog scale (VAS) score ≥1 for pain and provided informed consent for participation. The Douleur Neuropathic (DN4) questionnaire (score ≥4) was used to determine symptoms and signs as well as the presence of NCP. RESULTS: The prevalence of NCP was associated with age <65 years [OR, 1.57; 95% CI, 1.270-1.934], disease duration >6 months (OR, 1.57; 95% CI, 1.232-2.012), stage IV cancer (OR, 0.75; 95% CI, 0.593-0.955), history of chemotherapy (OR, 1.74; 95% CI, 1.225-2.472), and moderate-to-severe cancer pain (OR, 2.05; 95% CI, 1.671-2.524) after multivariate analysis. The most common descriptive symptoms of NCP were tingling, electric shock, and pins and needles. For NCP patients in the presence or absence of the clinical predictors, pins and needles (p = 0.001) and painful cold (p<0.001) symptoms were significantly frequent in patients with moderate-to-severe pain. Tingling, numbness, and touch hypoesthesia (p = 0.022, 0.033, 0.024, respectively) were more frequent in those with longer cancer duration and hyperesthesia (p = 0.024) was more frequent in young patients. CONCLUSION: Age <65 years, disease duration >6 months, stage IV cancer, history of chemotherapy, and moderate-to-severe cancer pain, were identified as predictors of NCP. Some symptoms and signs of NCP were associated with these predictors. Further studies are warranted on the pathogenesis and management of NCP with respect to the symptoms and signs, and factors associated with pain severity in Korean patients.
Asunto(s)
Dolor en Cáncer , Neoplasias , Neuralgia , Dimensión del Dolor , Encuestas y Cuestionarios , Factores de Edad , Anciano , Dolor en Cáncer/diagnóstico , Dolor en Cáncer/epidemiología , Dolor en Cáncer/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Neoplasias/fisiopatología , Neuralgia/diagnóstico , Neuralgia/epidemiología , Neuralgia/fisiopatología , PrevalenciaRESUMEN
BACKGROUND: Accurate and rapid clinical decisions based on real-world evidence are essential for patients with cancer. However, the complexity of chemotherapy regimens for cancer impedes retrospective research that uses observational health databases. OBJECTIVE: The aim of this study is to compare the anticancer treatment trajectories and patterns of clinical events according to regimen type using the chemotherapy episodes determined by an algorithm. METHODS: We developed an algorithm to extract the regimen-level abstracted chemotherapy episodes from medication records in a conventional Observational Medical Outcomes Partnership (OMOP) common data model (CDM) database. The algorithm was validated on the Ajou University School Of Medicine (AUSOM) database by manual review of clinical notes. Using the algorithm, we extracted episodes of chemotherapy from patients in the EHR database and the claims database. We also developed an application software for visualizing the chemotherapy treatment patterns based on the treatment episodes in the OMOP-CDM database. Using this software, we generated the trends in the types of regimen used in the institutions, the patterns of the iterative chemotherapy use, and the trajectories of cancer treatment in two EHR-based OMOP-CDM databases. As a pilot study, the time of onset of chemotherapy-induced neutropenia according to regimen was measured using the AUSOM database. The anticancer treatment trajectories for patients with COVID-19 were also visualized based on the nationwide claims database. RESULTS: We generated 178,360 treatment episodes for patients with colorectal, breast, and lung cancer for 85 different regimens. The algorithm precisely identified the type of chemotherapy regimen in 400 patients (average positive predictive value >98%). The trends in the use of routine clinical chemotherapy regimens from 2008-2018 were identified for 8236 patients. For a total of 12 regimens (those administered to the largest proportion of patients), the number of repeated treatments was concordant with the protocols for standard chemotherapy regimens for certain cases. In addition, the anticancer treatment trajectories for 8315 patients were shown, including 62 patients with COVID-19. A comparative analysis of neutropenia showed that its onset in colorectal cancer regimens tended to cluster between days 9-15, whereas it tended to cluster between days 2-8 for certain regimens for breast cancer or lung cancer. CONCLUSIONS: We propose a method for generating chemotherapy episodes for introduction into the oncology extension module of the OMOP-CDM databases. These proof-of-concept studies demonstrated the usability, scalability, and interoperability of the proposed framework through a distributed research network.
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Advanced breast cancer frequently metastasizes to the skeleton causing major mobility issues and hazards to quality of life. To manage osteolytic bone metastasis, bone-modifying agents and chemotherapy are recommended as the standard of care. Here, we investigated serologic biomarkers that might be associated with prognosis in breast cancer patients treated with zoledronic acid (ZA) and taxane-based chemotherapy. We collected serum samples from breast cancer patients with bone metastasis who received taxane plus ZA as palliative treatment. Fourteen biomarkers of angiogenesis, immunogenicity, and apoptosis were assessed, and the correlation between serum cytokine levels and patient's prognosis was statistically analyzed. Sixty-six patients were enrolled, and samples from 40 patients were analyzed after laboratory quality control. Patients with low baseline PDGF-AA, high IFN-γ, low MCP-2, low TGF-ß1, and low TNF-α were significantly associated with longer progression-free survival (PFS). Decreasing VEGF and TNF-α and increasing FGF-2 and PDGF-AA in the early treatment phase indicated longer PFS. In univariate and multivariate analyses, low TGF-ß1 and TNF-α and high IFN-γ at baseline were associated with a significantly low hazard ratio for disease progression. Further, we designed a risk score with TGF-ß1, TNF-α, and IFN-γ levels, which could prognosticate patients for PFS. In conclusion, serum cytokine level, such as TGF-ß1, TNF-α, and IFN-γ, could be a potential prognostic biomarker for breast cancer patients with bone metastasis treated with ZA and taxane-based chemotherapy.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Citocinas/sangre , Citocinas/uso terapéutico , Taxoides/uso terapéutico , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Ácido ZoledrónicoRESUMEN
BACKGROUND: Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center. METHODS: This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution. RESULTS: With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection. CONCLUSIONS: Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy.