BackgroundThe prognostic value of gender and age in the survival of nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT) is unclear. Several studies have suggested a female advantage in the prognosis of solid tumors. We investigated the relationship between gender differences and disease outcome in NPC patients treated with IMRT in South China.MethodsA total of 299 patients with non-disseminated NPC were analyzed retrospectively. IMRT was delivered with a simultaneous modulated, accelerated radiotherapy boost technique at prescribed doses of 70 Gy/30 fractions/6 weeks to the primary tumor (GTVp) and positive neck nodes (GTVn), 60Gy (2.0 Gy/day) to the clinical target volume (CTV) and upper neck region and 54 Gy (1.8 Gy/day) to the clinically negative low neck. A median boost dose of 9.2 Gy (4–20 Gy) was administered to patients with persistent disease at the primary site.ResultsWith a median follow-up of 52 months, the male patients had a significantly unfavorable 5-year OS (70.7% compared to 94.1%, P < 0.001), DPFS (71.5% compared to 87.3%, P = 0.029) and DMFS (77.2% compared to 89.7%, P = 0.036) than the female patients. In patients younger than 45, the male patients had a poorer 5-year OS (66.8% compared to 91.2%, P = 0.008), DPFS (59.9% compared to 91.2%, P = 0.005) and DMFS (66.4% compared to 94.0%, P = 0.004) than the female patients. For patients older than 45, only the 5-year OS (72.2% compared to 96.0%, P = 0.001) was significantly different.ConclusionsGender and age are strong independent prognostic factors for NPC in this study. We are the first to report that younger male patients were more likely to have distant metastases and exhibited inferior overall survival and disease progression-free survival rates compared to other patients.

IntroductionWe report the efficacy and safety of crizotinib treatment among Chinese patients with advanced-stage NSCLC.MethodsWe retrospectively analyzed patients with EML4-ALK positive advanced NSCLC who were treated with crizotinib from May 2012 to Aug 2013. Baseline clinical parameters, treatment protocol, response to therapy and survival were noted. The primary goal was to evaluate the efficacy of crizotinib in patients who were previously treated patients or who had poor ECOG performance status (PS).ResultsForty patients were evaluable for safety and efficacy. Median age was 43 years, 100% had adenocarcinoma and stage IV disease, and 42.5% were female. Six patients received frontline treatment with crizotinib, 17 patients had 1 prior treatment, and 17 patients had more than 2 lines of prior treatment. Patients received a median of 5 cycles of treatment (range 1–15 cycles). After the first cycle, 92.5% (37/40) patients archived partial remission (PR). At the end of the follow-up period, the overall PR rate was 70% (28/40), and progression of disease (PD) occurred in 30% of patients (12/40). The median PFS was 28 weeks (95% CI 15.4 to 40.5 weeks), and median OS was 40 weeks (95% CI 38.6 to 49.3 weeks). The most frequent treatment-related AEs were vomiting (47.5%), vision disorder (27.5%) and increased ALT/AST (42%); most toxicities were Grade 1/2. Observed treatment-related Grade 3/4 AEs included increased ALT/AST (10%) and vomiting (5%). The EML4-ALK fusion rate and number of prior chemotherapy cycles did not appear to significantly affect the efficacy of crizotinib. However, PS 0–2 patients had improved PFS (50 weeks vs. 24 weeks, p = 0.015).ConclusionsCrizotinib was safe, well-tolerated, and effective in Chinese patients with pre-treated ALK-rearranged NSCLC. QOL was improved and PS appears to have an effect on the efficacy of crizotinib, but prior treatment and ALK fusion rate do not.

BackgroundThe prognostic value of programmed death-ligand 1 (PD-L1) and BRAF expression in nasopharyngeal carcinoma (NPC) is not well-defined. In this study we investigated alterations in PD-L1, BRAF and EGFR by using immunohistochemistry analysis in a cohort of consecutively enrolled NPC patients.MethodsA retrospective review of 154 NPC patients form our previous study (BMC Cancer. 2013; 13:226) were conducted. Survival and prognostic impacts were analyzed based on PD-L1, BRAF and EGFR expression levels.ResultsOne hundred fifty four patients were included in this study. PD-L1 expression was detected in 87.7% of patients; 14.3% had 1–5% PD-L1 expression, 47.4% had 5–49% expression while 26% had ≥50% expression Higher PD-L1 expression was significantly associated with shorter PFS and OS. The median PFS was 25 months (95% CI 15.7–34.3 months) and OS was 35 months (95% CI 22.60–47.4 months) for patients with PD-L1 expression ≥50%; both median PFS and OS were not yet reached for patients with PD-L1 expression < 50%. PFS was significantly higher in BRAF mutation positive patients (5-year PFS: 55.1% vs. 30.8%, P = 0.044).ConclusionTumor PD-L1 expression and BRAF mutation are associated with poor outcomes in patients with NPC. This study was retrospectively registered in ClinicalTrials.gov (NCT03989297) on 2019-6-18.

Osimertinib showed encouraging efficacy in patients with advanced EGFR T790M-positive NSCLC in previous randomized controlled trials. This real-world study aimed to evaluate the effectiveness and safety of osimertinib in a real-world setting. This observational study (NCT03133234) included 74 patients with metastatic EGFR T790M-positive NSCLC who progressed on prior EGFR TKI therapy and received osimertinib between May 2016 and April 2018 at the Kiang Wu Hospital in Macau. Response rate (RR) and other endpoints (progression-free survival [PFS], overall survival [OS], disease control rate [DCR], stable disease rate, and adverse events) were assessed. Survival data were estimated using the Kaplan-Meier method. All patients had stage IV lung adenocarcinoma and 25.6% had brain metastases; median age was 58 years (range 28–84 years) and 83.8% of patients had received at least three prior lines of treatment. The median duration of osimertinib treatment was 8 months (range, 1–25 months). RR and DCR were 67.5% (95% CI 56.9–78.1) and 79.8% (95% CI 70.7–88.9), respectively, while 12.1% had stable disease. The median PFS was 9.0 months (95% CI 6.7–11.2 months), and the median OS was 12.0 months (95% CI 8.8–15.1 months). Nausea (25.8%) and decreased appetite (20.2%) were the most common adverse events associated with osimertinib treatment. Even though most patients had at least three lines of prior treatment, real-world RR and PFS with osimertinib in this study were consistent with those from randomized controlled trials; no new safety signals were observed.

Background: Irreversible EGFR-TKI monotherapies showed only moderate efficacy after AR to reversible EGFR-TKIs. Preclinical studies suggested that addition of Bev to EGFR-TKIs could overcome AR. Methods: ECOG PS 0-2 patients (pts) with EGFR-mutant NSCLC after AR to EGFR-TKIs were enrolled at any lines. Rebiopsy was essential to confirm T790M status after AR. Afa was prescribed at 30 mg, and Bev administered at 15 mg/kg tri-weekly until progression. Primary endpoint was response rate (RR). Results: Between October 2014 and May 2017, 32 eligible pts were evaluated. Median age was 66 (range, 48-86). Twenty-one (66%) pts were female, and 21 (66%) were never smoker. Mutation subtypes were 20 (63%) Del-19, 11 (34%) L858R, and 1 (3%) L861Q. T790M was detected in 14 (44%) pts. Median number of prior regimens was 4 (range, 1-10). First prior TKIs were 19 (60%) gefitinib, 10 (31%) erlotinib or 3 (9%) Afa. Six pts obtained partial response and 23 stable disease, resulting in RR of 18.8% (95% confidence interval [CI], 7.2-36.4%) and disease control rate of 90.7% (95% CI, 75.0-98.0%). Median progression-free survival (PFS) and overall survival were 6.3 (95% CI, 3.9-8.7) months and not reached, respectively. RR and median PFS of T790Mþ vs. T790M-were 14.3% vs. 22.2% (p ¼ 0.2094) and 6.3 vs. 7.1 months (p ¼ 0.7910), respectively. RR and median PFS of Del-19 vs. L858R were 20.0% vs. 11.1% (p ¼ 0.9024) and 6.3 vs. 5.1 months (p ¼ 0.7777), respectively. Afa dosage was reduced to 20 mg in 17 (53%) pts and increased to 40 mg in 2 (6%) pts. Median number of Bev administrations was 6 (range, 2-14). Bev was interrupted in 5 (16%) pts. Adverse events grade 3 (incidence 5%): anemia (6%); mucositis (6%); anorexia (6%); paronychia (25%); hypertension (41%); and proteinuria (19%) were observed. There were no treatment-related deaths, interstitial lung disease, nor Bev-associated severe bleedings.Conclusions: Afa þ Bev demonstrated clinical efficacy and safety after AR to EGFR-TKIs. It could be a therapeutic salvage option for NSCLC with AR to EGFR-TKIs, especially for T790M-populations whose therapeutic options are limited. Legal entity responsible for the study: N/A Funding: None Disclosure: All authors have declared no conflicts of interest.424P Does afatinib plus bevacizumab combination therapy induce positive conversion of T790M in previously T790M-negative patients?