Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

BACKGROUND: Among patients with resected, epidermal growth factor receptor (EGFR)-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival. METHODS: In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: Of 682 patients who underwent randomization, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis. CONCLUSIONS: Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).

LABS score- a prognostic tool for FOLFOX4-treated advanced hepatocellular carcinoma and real-world efficacy: a single-center retrospective study.

BACKGROUND: No widely used prognostic tool exists to demonstrate the benefit of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) in patients with advanced hepatocellular carcinoma (HCC). We aimed to establish a prognostic score and demonstrate the real-world efficacy of FOLFOX4 chemotherapy in Thai patients. METHODS: Between August 2017 and December 2021, we identified 58 FOLFOX4-treated patients with HCC. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were assessed. The prognostic score was constructed by stepwise Cox proportional hazards regression analysis to select variables for the best model with the lowest Akaike information criterion from all potential variables. RESULTS: Forty-four patients (76%) received FOLFOX4 as first-line therapy. The ORR in the entire cohort was 8.6%, and the disease control rate was 29.3%. The PFS and OS were 3.7 and 4.8 months, respectively. Four clinically relevant variables were included in the new prognostic score to predict 6-month OS: L, the presence of lung metastasis; A, alcoholic cirrhosis; B, elevated total bilirubin level; and S, sorafenib-naïve status. Using the LABS score, patients were classified into low-, intermediate-, and high-risk groups, demonstrating OS values of 9.3, 4.2, and 2.1 months, respectively (p < 0.0001). The C-index and area under the receiver-operating characteristic curve of the score were 0.71 and 0.73, respectively. CONCLUSIONS: The proposed LABS score could discriminate patients who would derive benefit from FOLFOX4 chemotherapy. FOLFOX4 chemotherapy is an option for patients who cannot receive immunotherapy and targeted therapy, particularly those with a low-risk score. However, further validation of this model via larger cohorts is warranted.

Utility of prophylactic percutaneous endoscopic gastrostomy tube in head and neck cancer patients undergoing concurrent chemoradiation: A prospective observational cohort.

PURPOSE: The necessity of prophylactic percutaneous endoscopic gastrostomy (PPEG) before concurrent chemoradiation (CCRT) in head and neck cancer (HNC) patients remains uncertain. We evaluated the utilization rate of PPEG tube. Weight changes and tube dependence were also assessed. MATERIALS AND METHODS: This prospective cohort study evaluated the utilization rate of PPEG tube in patients with newly diagnosed HNC undergoing CCRT. Baseline characteristics, nutrition status, and weight loss data were collected and compared between use and non-use groups. RESULTS: 110 patients (94.8%) used PPEG tube (70 fully-used and 40 partially-used groups). Non-users had a tendency to lose weight more than partially and fully-used groups; 9.13%, 3.42%, and 1.95%, respectively (p = 0.085). Fully-used group had significantly longer time of tube dependence than partially-used group, 7.0 months versus 4.9 months (p = 0.012). The type of PPEG tube use (full use or partial use) and presence of dysphagia were significantly related to tube dependence. The time ratio of tube dependence for partially-used patients versus fully-used patients was 0.82 (95% CI: 0.68-0.99) (p = 0.039). The time ratio for patients with symptoms of dysphagia was 1.29 (95% CI: 1.02-1.63) (p = 0.032). At the end of CCRT, 96.6% of patients agreed that PPEG tube was necessary. CONCLUSION: We recommend PPEG for patients undergoing CCRT. Partial use of PPEG with continuous oral intake as tolerated is strongly encouraged to maintain weight, and to reduce risk of tube dependence. Future study to evaluate effective swallowing exercise is warranted.

Benefits of prophylactic percutaneous gastrostomy in patients with nasopharyngeal cancer receiving concurrent chemoradiotherapy: A multicenter analysis.

PURPOSE: Prophylactic percutaneous endoscopic gastrostomy (PPEG) is widely used for patients with head and neck cancer undergoing concurrent chemoradiation (CCRT). Nevertheless, the necessity of its use in patients with nasopharyngeal cancer (NPC) is uncertain. This study aimed to evaluate the benefits of PPEG on prevention of weight loss and treatment tolerance in patients with NPC receiving CCRT. MATERIALS AND METHODS: A retrospective multicenter chart review of 904 patients, 378 in the PPEG group and 526 in the non-PPEG group, was conducted. Baseline characteristics, weight loss, and treatment tolerance were analyzed and compared between the two groups. RESULTS: There was no significant difference in the mean baseline body mass index (BMI) between the groups. At the end of CCRT, no difference in weight loss was found between the 2 groups (non-PPEG group, 6.6%; PPEG group, 5.9%). Nonetheless, the subgroup analysis demonstrated that a baseline BMI < 18.5 kg/m2 (underweight) and non-intensity-modulated radiation therapy (IMRT) technique were independent factors associated with prevention of weight loss by PPEG. More patients in the PPEG group were able to complete planned cycles of chemotherapy (73.3% vs. 49.0%, P < .0001). CONCLUSION: Although the benefits of PPEG on prevention of weight loss were not observed for the entire cohort, we found a potentially protective effect of PPEG in some subgroups of patients. Additionally, PPEG significantly enhanced chemotherapy tolerance. Therefore, PPEG tube insertion should be strongly considered for patients with NPC receiving CCRT, particularly for underweight patients and those undergoing a non-IMRT technique.

Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). METHODS: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival. RESULTS: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%). CONCLUSIONS: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).

Optimal cumulative dose of cisplatin for concurrent chemoradiotherapy among patients with non-metastatic nasopharyngeal carcinoma: a multicenter analysis in Thailand.

BACKGROUND: Chemoradiotherapy (CRT) with high cumulative doses (CDs) of cisplatin has been considered the standard of care for non-metastatic nasopharyngeal carcinoma (NPC). However, given most patients' inability to tolerate high CDs due to cisplatin-related toxicities, the optimal CD of cisplatin during CRT remains undetermined. METHODS: Patients with non-metastatic NPC who received CRT with cisplatin between 2007 and 2017 were identified through the Thai head and neck cancer multicenter database and then categorized according to cisplatin CD (mg/m2) received. All complications and cisplatin-related toxicities during CRT were recorded. RESULTS: We identified 779 non-metastatic NPC patients receiving low (≤150; n = 97), intermediate (151-250; n = 411), and high (> 250; n = 271) CDs of cisplatin. Low CD patients had significantly lower mean actual radiation dose (p < 0.001) and more radiotherapy delay (p = 0.010), while intermediate CD patients had the least hospitalization (p < 0.001). Overall, 39.3% of the patients experienced cisplatin-related toxicity, which was associated with poor overall survival (OS) (p = 0.001). Acute kidney injury was observed in 7% in all patients, which was highest among low CD patients (15.5%; p = 0.002). Intermediate CD patients had significantly longer median OS than the low and high groups (64 vs. 49.8 vs. 53.2, respectively; p = 0.015). Univariate, but not multivariate, analysis showed that CD of cisplatin was significantly associated with OS. CONCLUSION: CD of cisplatin during CRT was not an independent prognostic factor for OS. An intermediate CD induced minimal toxicity without compromising survival and should be considered the optimal CD. Nonetheless, a randomized phase 3 study evaluating the optimal CD of cisplatin is warranted.

Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) pathway activation in squamous cell carcinoma of the head and neck contributes to treatment resistance and disease progression. Buparlisib, a pan-PI3K inhibitor, has shown preclinical antitumour activity and objective responses in patients with epithelial malignancies. We assessed whether the addition of buparlisib to paclitaxel improves clinical outcomes compared with paclitaxel and placebo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. METHODS: In this multicentre, randomised, double-blind, placebo-controlled phase 2 study (BERIL-1), we recruited patients aged 18 years and older with histologically or cytologically confirmed recurrent and metastatic squamous cell carcinoma of the head and neck after disease progression on or after one previous platinum-based chemotherapy regimen in the metastatic setting. Eligible patients were enrolled from 58 centres across 18 countries and randomly assigned (1:1) to receive second-line oral buparlisib (100 mg once daily) or placebo, plus intravenous paclitaxel (80 mg/m2 on days 1, 8, 15, and 22) in 28 day treatment cycles. Randomisation was done via a central patient screening and randomisation system with an interactive (voice and web) response system and stratification by number of previous lines of therapy in the recurrent and metastatic setting and study site. Patients and investigators (including local radiologists) were masked to treatment assignment from randomisation until the final overall survival analysis. The primary endpoint was progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in all randomly assigned patients. Efficacy analyses were done on the intention-to-treat population, whereas safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received. This trial is registered with ClinicalTrials.gov, number NCT01852292, and is ongoing but no longer enrolling patients. FINDINGS: Between Nov 5, 2013, and May 5, 2015, 158 patients were enrolled and randomly assigned to receive either buparlisib plus paclitaxel (n=79) or placebo plus paclitaxel (n=79). Median progression-free survival was 4·6 months (95% CI 3·5-5·3) in the buparlisib group and 3·5 months (2·2-3·7) in the placebo group (hazard ratio 0·65 [95% CI 0·45-0·95], nominal one-sided p=0·011). Grade 3-4 adverse events were reported in 62 (82%) of 76 patients in the buparlisib group and 56 (72%) of 78 patients in the placebo group. The most common grade 3-4 adverse events (occurring in ≥10% of patients in the buparlisib group vs the placebo group) were hyperglycaemia (17 [22%] of 76 vs two [3%] of 78), anaemia (14 [18%] vs nine [12%]), neutropenia (13 [17%] vs four [5%]), and fatigue (six [8%] vs eight [10%]). Serious adverse events (regardless of relation to study treatment) were reported for 43 (57%) of 76 patients in the buparlisib group and 37 (47%) of 78 in the placebo group. On-treatment deaths occurred in 15 (20%) of 76 patients in the buparlisib group and 17 (22%) of 78 patients in the placebo group; most were caused by disease progression and none were judged to be related to study treatment. INTERPRETATION: On the basis of the improved clinical efficacy with a manageable safety profile, the results of this randomised phase 2 study suggest that buparlisib in combination with paclitaxel could be an effective second-line treatment for patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck. Further phase 3 studies are warranted to confirm this phase 2 finding. FUNDING: Novartis Pharmaceuticals Corporation.

Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy. METHODS AND FINDINGS: HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2 weekly. The primary endpoint was clinical benefit; secondary endpoints were objective response (OR), duration of OR, and progression-free survival (PFS). Of 26 patients treated with afatinib monotherapy, clinical benefit was achieved in 9 patients (35%), 0 of 7 trastuzumab-treated patients and 9 of 19 trastuzumab-naïve patients. Following disease progression, 10 patients received afatinib plus vinorelbine, and clinical benefit was achieved in 2 of 4 trastuzumab-treated and 0 of 6 trastuzumab-naïve patients. All patients had treatment-related adverse events (AEs). Whole-exome sequencing of tumour biopsies taken before treatment and following disease progression on afatinib monotherapy was performed to assess the mutational landscape of IBC and evolutionary trajectories during therapy. Compared to a cohort of The Cancer Genome Atlas (TCGA) patients with HER2-positive non-IBC, HER2-positive IBC patients had significantly higher mutational and neoantigenic burden, more frequent gain-of-function TP53 mutations and a recurrent 11q13.5 amplification overlapping PAK1. Planned exploratory analysis revealed that trastuzumab-naïve patients with tumours harbouring somatic activation of PI3K/Akt signalling had significantly shorter PFS compared to those without (p = 0.03). High genomic concordance between biopsies taken before and following afatinib resistance was observed with stable clonal structures in non-responding tumours, and evidence of branched evolution in 8 of 9 tumours analysed. Recruitment to the trial was terminated early following the LUX-Breast 1 trial, which showed that afatinib combined with vinorelbine had similar PFS and OR rates to trastuzumab plus vinorelbine but shorter overall survival (OS), and was less tolerable. The main limitations of this study are that the results should be interpreted with caution given the relatively small patient cohort and the potential for tumour sampling bias between pre- and post-treatment tumour biopsies. CONCLUSIONS: Afatinib, with or without vinorelbine, showed activity in trastuzumab-naïve HER2-positive IBC patients in a planned subgroup analysis. HER2-positive IBC is characterized by frequent TP53 gain-of-function mutations and a high mutational burden. The high mutational load associated with HER2-positive IBC suggests a potential role for checkpoint inhibitor therapy in this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325428.

The Performance of a Survival Nomogram and Albumin-Bilirubin Grade as Prognostic Tools in Advanced Hepatocellular Carcinoma Treated with FOLFOX4.

BACKGROUND: The ability of the survival nomogram developed in the EACH study and albumin-bilirubin (ALBI) grade to predict the survival of advanced hepatocellular carcinoma (HCC) patients receiving oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) remains unvalidated. Here, we comprehensively evaluated these prognostic tools. METHODS: The survival nomogram and ALBI grade of each patient were assessed, and the area under the receiver operating curve (AUROC) and Harrell's C-index for the risk classification model were calculated. RESULTS: Overall, 76 HCC patients who received FOLFOX4 between August 2017 and June 2023 were included. The survival nomogram classified patients into low-, intermediate-, and high-risk groups, with a median overall survival (OS) of 9.82, 10.64, and 3.70 months, respectively (p = 0.23). The AUROC was 0.621 and Harrell's C-index was 0.589. However, the ALBI grade categorized all patients into grade 1, 2, and 3, with a median OS of 9.82, 6.83, and 1.58 months, respectively (p = 0.00024). The AUROC was 0.663 and Harrell's C-index was 0.663. CONCLUSION: The ALBI grade can be a potential prognostic tool. However, the survival nomogram does not provide clear discrimination. Therefore, FOLFOX4 should be an option for patients with ALBI grade 1 who cannot receive immunotherapy or targeted therapy. Additional prospective studies with a larger cohort are warranted to validate the survival nomogram and ALBI grade as prognostic tools.

Orbital Metastasis as the First Manifestation of Hepatocellular Carcinoma, and Its Effective Treatment with Combined Dual Immunotherapy: A Case Report and Review of the Literature.

BACKGROUND Orbital metastasis originating from hepatocellular carcinoma (HCC), particularly as an initial manifestation in patients without a known history of HCC, is rare. Few reports exist on the treatment of patients having HCC with orbital metastasis using targeted therapy or immunotherapy. CASE REPORT We report a case of advanced-stage HCC in a 65-year-old man who first presented with progressive, painless blurred vision and proptosis of the right eye for 2 weeks. The patient had no history of chronic liver disease or cancer. Computed tomography revealed an enhancing hyperdense extraconal mass in the right orbit; a biopsy revealed metastatic HCC. Abdominal CT, which was performed to investigate the primary cancer, revealed a 1.2×1.6-cm arterial-enhancing nodule with venous washout in hepatic segment 5, associated with liver cirrhosis. The patient's serum alpha-fetoprotein level was 70.27 ng/dL. Chest computed tomography revealed lung metastasis. Thus, first-line systemic therapy combining durvalumab and tremelimumab was initiated alongside palliative radiotherapy targeting the right orbit, which began 1 week after the first dose of dual immunotherapy. The patient had significant clinical improvement, reduced proptosis, and serum alpha-fetoprotein levels. CONCLUSIONS Although orbital metastasis is a rare manifestation of HCC, physicians should recognize and consider aggressive investigations for early diagnosis, especially in patients with existing risk factors for HCC. Dual immunotherapy with durvalumab and tremelimumab in combination with radiotherapy can be considered a potential treatment option for managing advanced HCC with orbital metastasis.

Comparing the Efficacy of Carboplatin plus 5-Fluorouracil, Cisplatin plus 5-Fluorouracil, and Best Supportive Care for Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score Analysis from a Tertiary Hospital in Southern Thailand.

Background: Although cisplatin plus 5-fluorouracil (5-FU) is the standard first-line treatment for advanced-stage esophageal squamous cell carcinoma (ESCC), carboplatin was substituted for cisplatin in cisplatin-ineligible patients. The efficacy of carboplatin plus 5-FU for advanced-stage ESCC remains unreported. Methods: This retrospective study analyzed first-line treatment-carboplatin plus 5-FU, cisplatin plus 5-FU, or best supportive care (BSC)-in advanced-stage ESCC patients at a tertiary hospital in Thailand (2012-2022). Survival was assessed using the Kaplan-Meier method, compared via the log-rank test, and adjusted through propensity score matching. Significance was set at p < 0.05. Results: Of 256 patients, 39.9% received carboplatin plus 5-FU, 27.7% cisplatin plus 5-FU, and 32.4% BSC. Carboplatin was significantly associated with older age, poorer performance status, more comorbidities, chronic kidney disease, and lower creatinine clearance. Median overall survival (OS) for carboplatin plus 5-FU, cisplatin plus 5-FU, and BSC was 8.05 (HR 0.31 [0.23, 0.43] vs. BSC, p < 0.001; HR 1.06 [0.78, 1.44] vs. cisplatin plus 5-FU, p = 0.7), 8.43, and 3.64 months, respectively. No significant OS difference was observed between carboplatin and cisplatin treatments after propensity score matching. Median progression-free survival (PFS) and objective response rates (ORR) showed no significant difference between carboplatin and cisplatin treatments. Conclusions: Despite less favorable baseline characteristics of patients receiving carboplatin plus 5-FU, this combination exhibited comparable OS, PFS, and ORR to cisplatin plus 5-FU in real-world scenarios. Furthermore, it significantly improved OS over BSC. Consequently, carboplatin plus 5-FU should be considered as an alternative regimen, particularly for advanced-stage ESCC patients who are ineligible for cisplatin.

HPV-Related Oropharyngeal Cancer in Southern Thailand: Proportion Trend and Survival Outcome.

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is one of the major etiologies of oropharyngeal squamous cell carcinoma (OPSCC). This study aimed to determine the proportion, temporal trend, and prognostic significance of HPV-related OPSCC in Thai patients. METHODS: The study included patients with OPSCC who were treated at Songklanagarind Hospital (Songkhla, Southern Thailand) from 2009 to 2020. HPV status was screened by p16 expression using immunohistochemistry and confirmed by real-time polymerase chain reaction. Cox regression was used to determine prognostic significance. RESULTS: The overall proportion of HPV+ OPSCC was 15.3% (95% confidence interval [CI]: 12.1-18.5) with a slightly increased proportion from 10.6% in 2009-2010 to 16.5% (2019-2020) (P for trend = 0.166). Among the HPV+ cases, HPV16 was detected in 65.3%, HPV18 in 34.7%, and other high-risk HPV types in 24%. Patients with P16+ or HPV+ OPSCC had significantly better overall survival (hazard ratio [HR]: 0.63, 95% CI: 0.45-0.90 and HR: 0.63, 95% CI: 0.45-0.88, respectively). CONCLUSION: Thai patients in the southern region have a low proportion of HPV-related OPSCC with an increasing trend. Both P16 expression and HPV DNA status are strong independent prognostic factors of OPSCC.

Summary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

This is a summary of the original article ?Overall survival with osimertinib in resected EGFR-mutated NSCLC.Ë® Osimertinib blocks the activity of the epidermal growth factor receptor (EGFR) on cancer cells, causing cancer cell death and tumor shrinkage, and is an effective treatment for EGFR-mutated non-small cell lung cancer (NSCLC). The ADAURA study assessed the effects of osimertinib versus placebo in patients with EGFR-mutated (exon 19 deletion or L858R) early stage (IB-IIIA) NSCLC removed by surgery (resected). Previous results from ADAURA demonstrated that patients treated with osimertinib stayed alive and cancer-free (disease-free survival) significantly longer than patients who received placebo. Recent data showed the overall length of time patients were alive after starting treatment (overall survival). In both the primary stage II-IIIA and overall stage IB-IIIA populations, patients in the osimertinib group had a significant 51% reduction in the risk of death compared with the placebo group. The data demonstrated that osimertinib after surgery significantly improved overall survival in patients with resected, EGFR-mutated, stage IB-IIIA NSCLC.

Nineteen-year, real-world experience of first-line combination chemotherapy in patients with metastatic colorectal cancer: a propensity score analysis from southern Thailand.

OBJECTIVE: Combination fluoropyrimidine-based chemotherapy is the standard first-line treatment for metastatic colorectal cancer (CRC). We performed a propensity score (PS)-based analysis to report our real-world experience with long-term follow-up of this regimen for metastatic CRC. METHODS: In this retrospective study, 170 patients with newly diagnosed metastatic CRC treated with first-line combination chemotherapy between January 2003 and March 2021 were identified. Cox proportional hazards regression analysis and PS-based approaches with the logistic regression model were adopted, and the results were compared. RESULTS: The hazard ratio for overall survival (OS) in the oxaliplatin- and irinotecan-based groups was 0.79 (95% confidence interval = 0.56-1.11), and the median OS times in these groups were 16.8 and 13.0 months, respectively. The median time to progression (TTP) for these regimens were 9.0 and 8.9 months, respectively. The objective response rates for the oxaliplatin- and irinotecan-based groups were 42.7% and 34.6%, respectively. OS and TTP did not differ between these regimens in all PS matching models. CONCLUSIONS: First-line treatment using fluoropyrimidine-based chemotherapy regimens in combination with oxaliplatin or irinotecan in patients with metastatic CRC provided comparable efficacy and tolerable toxicity profiles in a real-world setting with long-term follow-up.

Real-world evidence of cisplatin versus carboplatin in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: A multicenter analysis.

BACKGROUND: Though concurrent chemoradiotherapy (CCRT) with cisplatin remains a standard of care for patients with locally advanced nasopharyngeal carcinoma (LA-NPC), carboplatin has alternatively been used without sufficient supportive evidences. Thus, we evaluated an efficacy and tolerability of carboplatin CCRT compared with cisplatin in LA-NPC patients. METHODS: Patients with LA-NPC treated with CCRT were identified through the Thai multicenter head and neck cancer database. Patient tolerability and survival were analyzed and compared between regimens. Survivals were calculated by using the Kaplan-Meier method, and compared by the log-rank test. A p-value of <0.05 was considered statistically significant. RESULTS: A total of 135 of 980 patients (13.8%) were treated with carboplatin. Patients treated with carboplatin were significantly associated with older age (p < 0.001), smoking (p = 0.003), more comorbidity (p = 0.014), kidney disease (p = 0.016), and lower baseline creatinine clearance (p < 0.001). Intensity-modulated radiation therapy was used significantly more in the cisplatin group than carboplatin group (p < 0.001). Patients who received carboplatin were associated with delay (p = 0.049) and hospitalization (p = 0.006), whereas cisplatin CCRT had more dose reduction (p = 0.001). Patients treated with cisplatin had CCRT interruption from grade 3-4 mucositis (p = 0.019) more than carboplatin, whereas carboplatin had more grade 3-4 thrombocytopenia (p < 0.001). The 5-year overall survival (OS) of patients treated with cisplatin and carboplatin was 59% and 49%, respectively (p = 0.128). Cisplatin or carboplatin CCRT was not a significant predictor for OS and locoregional recurrence-free survival in multivariate analysis. CONCLUSIONS: Carboplatin CCRT provided acceptable efficacy and tolerability profiles in real-world practice. Carboplatin should be considered as an alternative regimen, particularly in cisplatin-ineligible patients with LA-NPC treated with CCRT.

Characteristics, Outcomes, and Factors Affecting Mortality in Hospitalized Patients with CAP Due to Different Variants of SARS-CoV-2 and Non-COVID-19 CAP.

The study was conducted from October 2020 to March 2022 in a province in southern Thailand. The inpatients with community-acquired pneumonia (CAP) and more than 18 years old were enrolled. Of the 1511 inpatients with CAP, COVID-19 was the leading cause, accounting for 27%. Among the patients with COVID-19 CAP, mortalities, mechanical ventilators, ICU admissions, ICU stay, and hospital costs were significantly higher than of those with non-COVID-19 CAP. Household and workplace contact with COVID-19, co-morbidities, lymphocytopenia and peripheral infiltration in chest imaging were associated with CAP due to COVID-19. The delta variant yielded the most unfavorable clinical and non-clinical outcomes. While COVID-19 CAP due to B.1.113, Alpha and Omicron variants had relatively similar outcomes. Among those with CAP, COVID-19 infection as well as obesity, a higher Charlson comorbidity index (CCI) and APACHE II score were associated with in-hospital mortality. Among those with COVID-19 CAP, obesity, infection due to the Delta variant, a higher CCI and higher APACHE II score were associated with in-hospital mortality. COVID-19 had a great impact on the epidemiology and outcomes of CAP.

Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma.

BACKGROUND: Programmed cell death receptor-1 (PD-1)-blocking antibodies are approved to treat metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) cases ineligible for curative surgery or radiation. Notwithstanding, some patients experience inadequate responses or severe immune-related adverse events (AEs), indicating the need for improved therapies. Cosibelimab is a high-affinity programmed cell death-ligand 1 (PD-L1)-blocking antibody that activates innate and adaptive immunity by blocking PD-L1 interaction with PD-1 and B7-1 receptors. It is an unmodified immunoglobulin G1 subtype with a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Here, we present results of the pivotal study of patients with metastatic CSCC from an open-label, multicenter, multiregional, multicohort, phase 1 trial of cosibelimab. METHODS: In this trial, participants with metastatic CSCC received cosibelimab 800 mg intravenously every 2 weeks. Primary endpoint was objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, V.1.1. Secondary endpoints included duration of response (DOR) and safety. RESULTS: Objective response was observed in 37 of 78 participants (47.4% (95% CI: 36.0% to 59.1%)), with median follow-up of 15.4 months (range: 0.4 to 40.5) as of data cut-off. Median DOR was not reached (range: 1.4+ to 34.1+ months), with response ongoing in 73.0% of participants. Common treatment-emergent AEs (≥15%) were fatigue (26.9%), rash (16.7%), and anemia (15.4%). Eighteen participants (23.1%) experienced immune-related AEs (grade 3: n=2 (2.6%); no grade 4/5). No treatment-related deaths were reported. CONCLUSIONS: Cosibelimab demonstrated clinically meaningful ORR and DOR and was associated with a manageable safety profile. TRIAL REGISTRATION NUMBER: NCT03212404.

Metastatic Primary Testicular Neuroendocrine Carcinoma Associated with Somatic Malignant Transformation of Teratoma: A Rare Case Report.

Testicular neuroendocrine tumor associated with teratoma is a rare disease. Very few cases have been reported in the literature, particularly cases involving visceral metastasis. Teratoma with somatic malignant transformation (SMT) is associated with a worse prognosis compared to teratoma without SMT. Previous data have suggested that chemotherapy regimens should be directed toward the transformed histology; however, those suggestions were based on patients with rhabdomyosarcoma, adenocarcinoma, and primitive neuroectodermal subtypes. To the best of our knowledge, only 2 cases with visceral metastasis have been reported, and a better outcome with the bleomycin/etoposide/cisplatin regimen, which responds strongly to germ cell tumors, has been reported in these cases. In contrast, 2 others with lymph node metastasis did not respond to these regimens. Here, we report a case of a patient with testicular neuroendocrine carcinoma associated with teratoma who achieved a good response to chemotherapy.

Frequency of PIK3CA mutations in different subsites of head and neck squamous cell carcinoma in southern Thailand.

BACKGROUND: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC. METHODS: Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations. RESULTS: The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations. CONCLUSIONS: The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.

Benefits of immunonutrition in patients with head and neck cancer receiving chemoradiation: A phase II randomized, double-blind study.

BACKGROUND & AIMS: The benefits of immunonutrition in patients with head and neck cancer (HNC), especially for those undergoing definitive concurrent chemoradiation (CCRT), remain unclear. We evaluated the benefits of immunonutrition regarding the prevention of severe oral mucositis. Secondary objectives included assessments of other treatment-related toxicities, changes of nutritional and inflammatory marker levels, treatment tolerance, and survival. METHODS: In total, 110 patients with HNC undergoing definitive CCRT including 3-week cycles of cisplatin were enrolled in our double-blind phase II study. Patients were randomly assigned to receive an immunonutrient formula containing omega-3-fatty acids, arginine, dietary nucleotides, and soluble fiber (n = 55) or an isocaloric isonitrogenous control (n = 55). All patients received the assigned product 5 consecutive days before each chemotherapy session. The proportion of patients with severe oral mucositis was compared between the immunonutrients and control groups. RESULTS: The rates of nasopharyngeal cancer (NPC) were 67% and 51% in the immunonutrients and control groups, respectively. All patients had 100% compliance to the assigned product. There was no difference of the proportion of patients with grade 3-4 oral mucositis between the two groups (62% vs. 67%, p = 0.690). At the time of analyses, survival tended to be better in the immunonutrients group. The 3-year progression-free survival rates were 69% (95% confidence interval [CI] = 55%-80%) and 44% (95% CI = 30%-57%) in the immunonutrients and control groups, respectively (p = 0.056), whereas the 3-year overall survival rates in these groups were 69% (95% CI = 54%-80%) and 50% (95% CI = 36%-66%; p = 0.065), respectively. In subgroup analyses according to the primary tumor location, the survival benefits were apparently maintained in patients with NPC. CONCLUSIONS: Although our study did not demonstrate a reduced risk of severe oral mucositis, we found that immunonutrition might improve survival. Larger studies are needed to determine the optimal dose and schedule of immunonutrition to prevent oral mucositis. In addition, randomized phase III trials evaluating the survival benefits of immunonutrition in patients with cancer are required, and NPC might be a primary malignancy of interest. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05101889.