Metastatic Nasopharyngeal Cancer Research Articles

Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial

Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. gov identifier: NCT02578641. A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC+ EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC+ EBV-CTL subjects. The median OS was 25.0 months in the GC+ EBV-CTL group and 24.9 months in the GC group (hazard ratio= 1.19; 95% confidence interval 0.91-1.56; P= 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. GC+ EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

899P Safety and efficacy of a novel CAR-T cell therapy (BRG01) targeting the Epstein-Barr Virus envelope glycoprotein in advanced metastatic nasopharyngeal cancer patients

899P Safety and efficacy of a novel CAR-T cell therapy (BRG01) targeting the Epstein-Barr Virus envelope glycoprotein in advanced metastatic nasopharyngeal cancer patients

PD-L1 expression as a potential predictor of immune checkpoint inhibitor efficacy and survival in patients with recurrent or metastatic nasopharyngeal cancer: a systematic review and meta-analysis of prospective trials.

The predictive value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal cancer (NPC) patients receiving immune checkpoint inhibitors (ICIs) remains controversial. This study aimed to evaluate the optimal threshold of PD-L1 expression in predicting the efficacy of ICIs in patients with recurrent or metastatic (R/M) NPC. A meta-analysis was performed by retrieving relevant literature from PubMed, EMBASE, and Cochrane Library databases. Data on the pooled risk ratio (RR), mean overall survival (OS), progression-free survival (PFS), overall response rate (ORR) with 95% confidence interval, and 1%, 10%, and 25% PD-L1 expression cutoff points were obtained to examine the role of PD-L1 as a biomarker in R/M NPC patients receiving immunotherapy. In total, 1,312 patients from 14 studies were included. An improvement in PFS was observed in both patients with PD-L1 ≥ 1% (RR = 0.76, 95% CI 0.62-0.92, P = 0.005) and those with PD-L1 < 1% (RR = 0.68, 95% CI: 0.35-1.32, P = 0.26) who received first-line treatment with immunotherapy, with no significant difference between these subgroups. The pooled ORR was significantly higher in patients with PD-L1 ≥ 1% (ORR = 0.37) than in those with PD-L1 < 1% (ORR = 0.22) (P < 0.01) undergoing subsequent-line treatment. However, when we used the PD-L1 cutoff values of 10% and 25%, there was no significant difference between the positive (PD-L1 expression ≥ the cutoff value) and negative (PD-L1 expression < the cutoff value) subgroups. PD-L1 ≥ 1% also tended to be associated with better PFS and OS. Our meta-analysis suggested that first-line immunotherapy could significantly improve PFS in R/M NPC patients, regardless of the PD-L1 expression levels. Positive PD-L1 expression (≥ 1%) might be a potential predictive biomarker for a better overall response to immunotherapy in R/M NPC patients in subsequent-line setting. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024495841 PROSPERO, identifier CRD42024495841.

Tumor cell-derived exosomal miR-193b-3p promotes tumor-associated macrophage activation to facilitate nasopharyngeal cancer cell invasion and radioresistances

BackgroundCommunication between cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) plays a crucial role in accelerating nasopharyngeal cancer (NPC) metastasis and radioresistance. However, the mechanisms through which NPC cells regulate the properties and activation of TAMs during NPC progression are not yet fully understood. MethodsA high-metastatic NPC subclone (HMC) and a low-metastatic NPC subclone (LMC) were screened from the CNE-2 cell line and exosomes were collected from HMCs and LMCs, respectively. The effects of HMC- and LMC-derived exosomes (HMC-Exos and LMC-Exos) on the regulation of TAM activation were evaluated by assessing the levels of inflammation-related or immunosuppression-related genes. The role of miRNA-193b-3p (miR-193b) in mediating communication between NPCs and TAMs was assessed using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot analysis, Transwell assays, and clonogenic survival assays. ResultsHMCs and HMC-Exos exhibited a greater capacity to facilitate macrophage protumorigenic activation than LMCs and LMC-Exos. miR-193b levels derived from HMC-Exos were higher than those from LMC-Exos, and miR-193b levels were higher in metastatic NPC tissue-derived TAMs than in non-metastatic NPC tissue-derived TAMs. The upregulated miR-193b was packaged into exosomes and transferred to macrophages. Functionally, miR-193b up-regulation accelerated TAM activation by directly targeting mitogen-activated protein/ERK kinase kinase 3 (MEKK3). As a result, miR-193b-overexpressed macrophages facilitated NPC cell invasion and radioresistance. ConclusionsThese data revealed a critical role for exosomal miR-193b in mediating intercellular communication between NPC cells and macrophages, providing a potential target for NPC treatment.

Effects of tislelizumab on health-related quality of life in patients with recurrent or metastatic nasopharyngeal cancer.

This study evaluated health-related quality of life (HRQoL) in the RATIONALE-309 (NCT03924986) intent-to-treat (ITT) population and in a subgroup of patients with liver metastases. Patients were randomized 1:1 to tislelizumab + chemotherapy or placebo + chemotherapy. As the secondary endpoint, HRQoL was evaluated using seven selected scores from the EORTC QLQ-C30 and QLQ Head and Neck Cancer module (QLQ-H&N35). Of 263 randomized patients in the ITT population (tislelizumab + chemotherapy n = 131, placebo + chemotherapy n = 132), 43% had liver metastases (tislelizumab + chemotherapy n = 56; placebo + chemotherapy n = 57). No differences in change in selected scores on the QLQ-C30 from baseline to cycle 4 or cycle 8 were observed for the ITT or liver metastases subgroup. No differences in selected QLQ-H&N35 scores were observed between the arms from baseline to cycle 4. In the ITT population and the liver metastases subgroup, a greater reduction from baseline to cycle 8 was observed in the tislelizumab + chemotherapy arm than the placebo + chemotherapy arm in QLQ-H&N35 pain score. At cycle 8 in the liver metastases subgroup, the tislelizumab + chemotherapy arm experienced greater improvement in the QLQ-H&N35 senses problems score than the placebo + chemotherapy arm. Differences in time to deterioration between arms were not observed. The current findings, along with improved survival and favorable safety, suggests that tislelizumab + chemotherapy represents a potential first-line treatment for recurrent or metastatic nasopharyngeal cancer.

Abstract 5660: Gene expression signatures from FFPE to predict recurrent metastatic nasopharyngeal cancer

Abstract Nasopharyngeal cancer (NPC) is an EBV-driven epithelial cancer endemic to Southeast Asia, Southern China and the Middle East. Accurate profiling of the gene expression of NPC has been challenging because of its intense inflammatory infiltrate, as well as the 3 - 4mm size of biopsies limiting the amount of available material. Here we present a large cohort of 339 micro-dissected gene expression libraries from formalin-fixed paraffin-embedded (FFPE) biopsies from NPC patients treated at the National University Health System, Singapore, as well as healthy controls. NPC tumors from patients who subsequently developed recurrent or metastatic disease (Group A), and patients who did not develop recurrent or metastatic disease (Group B) were profiled. Tumor epithelial and microenvironment compartments were separately obtained using laser-capture microdissection, followed by library preparation performed for RNA-Seq using an in-house specialised technique. Gene signatures for NPC tumor epithelial and microenvironment content were used to validate the purity of gene expression libraries. Our preliminary analysis revealed that primary, pre-treatment tumors from patients who subsequently developed recurrence (Group A) showed downregulation of processes related to interferon gamma and interferon alpha response (p-adj &amp;lt;0.001 for both), while processes related to epithelial-mesenchymal transition (p-adj &amp;lt; 0.05) were enriched compared to patients who remained healthy (Group B). In contrast to primary tumors, recurrent tumors in Group A were enriched for cellular respiration including oxidative phosphorylation (p-adj &amp;lt; 0.0001). Our approach highlights the utility of whole transcriptome profiling from small quantities of archival FFPE material. The gene signatures identified from the primary tumors of high-risk patients are biologically relevant and have the potential to be used in precision medicine to guide additional targeted intervention. Citation Format: Joshua K. Tay, Wei Keat Teo, Joseph W. Foley, Luvita Suryani, Bing Cheng Wu, Chor Hiang Siow, Kwok Seng Loh. Gene expression signatures from FFPE to predict recurrent metastatic nasopharyngeal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5660.

Cost-effectiveness of pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent or metastatic nasopharyngeal cancer

BackgroundProgrammed cell death protein 1 (PD-1) monoclonal antibody, pembrolizumab, is a promising drug for platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (NPC). We aimed to assess the cost-effectiveness of pembrolizumab compared with chemotherapy for Chinese patients in this NPC.MethodsThe cost-effectiveness of pembrolizumab versus chemotherapy was evaluated using a partitioned survival model with a 5-year boundary. Efficacy and toxicity data were derived from the KEYNOTE-122 trials. Economic indicators including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost were used. One-way analysis and probabilistic sensitivity analysis (PSA) were performed to explore the uncertainties. Additionally, various scenario analyses, including different pembrolizumab price calculations and discount rates were performed.ResultsPembrolizumab or chemotherapy alone respectively yielded 2.82 QALYs (3.96 LYs) and 2.73 QALYs (3.93 LYs) with an ICER of $422,535 per QALYs ($1,232,547 per LYs). This model was primarily influenced by the price of pembrolizumab. Furthermore, PSA indicated that pembrolizumab had none probability of being cost-effective compared with chemotherapy at a willingness-to- pay (WTP) of $38223. Scenario analyses revealed that irrespective of any potential price reduction or adjustments in the discount rate, no discernible impact on the ultimate outcome was observed.ConclusionPembrolizumab was less cost-effective for patients with platinum-pretreated, recurrent or metastatic NPC compared with chemotherapy in China.

Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial.

The strategy of dual blockade of TGF-β and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients. In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks. Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Thirty-eight patients were accrued (33 men; median age, 54 years). ORR was 23.7% (complete response, n=2; partial response, n=7). The median DOR was 19.2 months, median PFS was 2.3 months, median OS was 17.0 months, and 1-year OS rate was 63.2%. Unfortunately, 25 patients (65.7%) progressed within 8 weeks of treatment, 15 patients (39.5%) and 8 patients (21.1%) developed hyper-progressive disease (HPD) per RECIST v1.1 and tumor growth rate (TGR) ratio respectively. Sixteen patients (42.4%) experienced≥grade 3 treatment-related adverse events (TRAEs), most commonly anemia (n=9, 23.7%) and secondary malignancies (n=4, 10.5%). TRAEs led to permanent treatment discontinuation in 7 patients. Patients with strong suppression of plasma TGFβ1 level at week 8 were unexpectedly associated with worse ORR (9.1% vs 44.4%, P=0.046) and development of HPD. There was no correlation between PD-L1 expression and ORR. Bintrafusp alfa demonstrated modest activity in R/M NPC but high rates of HPD and treatment discontinuation secondary to TRAEs are concerning. The project was supported by Alice Ho Miu Ling Nethersole Charity Foundation Professorship Endowed Fund and Merck KGaA.

Cost-effectiveness analysis of first-line tislelizumab plus chemotherapy for recurrent or metastatic nasopharyngeal cancer.

Introduction: The RATIONALE-309 trial confirmed the significant efficacy and safety of tislelizumab plus chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). However, the economic benefits of this regimen are unclear. Therefore, this study aimed to evaluate the cost-effectiveness of adding tislelizumab to chemotherapy for R/M NPC from the perspective of the Chinese healthcare system. Methods: A Markov model was established to simulate the costs and outcomes of tislelizumab plus chemotherapy versus chemotherapy. The survival data came from the RATIONALE-309 trial. Only direct medical costs were considered, and utility values were referred to the literature. The incremental cost-effectiveness ratio (ICER) was used as the main outcome measure. Sensitivity analysis was performed to assess the effect of parameter uncertainty on the model. Additionally, subgroup analyses were performed. Results: The basic analysis showed that the cost of tislelizumab plus chemotherapy ($33,693) was $17,711 higher than that of chemotherapy ($15,982), but it also gained 1.05 QALYs more (2.72 QALYs vs. 1.67 QALYs), with an ICER of $16,859/QALY, which was lower than the willing-to-pay (WTP) of $36,289/QALY. The factors that most influenced the model were the utility of PD, the cost of tislelizumab, and the risk of platelet count decreased in tislelizumab plus chemotherapy group. The subgroup analysis also demonstrated that tislelizumab plus chemotherapy was cost-effective in the whole population regardless of EBV DNA level and PD-L1 expression level. Conclusion: Compared with chemotherapy alone, tislelizumab plus chemotherapy was cost-effective for the treatment of R/M NPC in China.

Abstract PO-008: Association of plasma Epstein-Barr virus DNA and clinical response in patients with recurrent and/or metastatic nasopharyngeal cancer treated with pembrolizumab or standard-of-care chemotherapy in KEYNOTE-122

Abstract PO-008: Association of plasma Epstein-Barr virus DNA and clinical response in patients with recurrent and/or metastatic nasopharyngeal cancer treated with pembrolizumab or standard-of-care chemotherapy in KEYNOTE-122

Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309)

Checkpoint inhibitors are effective in recurrent/metastatic nasopharyngeal cancer (R/M NPC). RATIONALE-309 (NCT03924986) randomized 263 treatment-naive R/M NPC patients to tislelizumab or placebo every 3weeks (Q3W), plus chemotherapy (Q3W for 4-6 cycles). At interim analysis, progression-free survival (PFS) was significantly longer with tislelizumab-chemotherapy versus placebo-chemotherapy (hazard ratio: 0.52; 95% confidence interval: 0.38, 0.73; p<0.0001). PFS benefit for tislelizumab-chemotherapy versus placebo-chemotherapy was observed regardless of programmed death-ligand 1 expression. PFS after next line of treatment and overall survival showed favorable trends for tislelizumab-chemotherapy versus placebo-chemotherapy. The safety profile was similar between arms. Gene expression profiling (GEP) identified immunologically "hot" tumors, and showed an activated dendritic cell (DC) signature was associated with tislelizumab-chemotherapy PFS benefit. Our results support that tislelizumab-chemotherapy should be considered as first-line treatment for R/M NPC, and GEP and activated DC signature results may help identify patients who might benefit most from immunochemotherapy treatment. VIDEO ABSTRACT.

Efficacy of Anti-PD1 Blockade in Treating Recurrent or Metastatic Nasopharyngeal Cancer: A Systematic Review and Meta-analysis

ObjectivesAnti-PD1 antibody has emerged as a promising immunotherapeutic option in patients with recurrent and/or metastatic nasopharyngeal cancers (RM-NPC). We aim to summarise existing evidence on the use of anti-PD1 antibodies in the treatment of these patients and compare its effectiveness with standard-of-care palliative chemotherapy. Our secondary aim is to explore potential combination therapies with anti-PD1 antibodies. Materials and MethodsPubMed, Embase and Cochrane databases were systematically searched for studies comparing the efficacy of various anti-PD1 antibodies in the treatment of RM-NPC (either as first or second line treatment) from inception to 2 September 2022. Meta-analyses were performed to correlate the various anti-PD1 antibodies with primary endpoints including overall response rate disease control rate (DCR), progression free survival (PFS) and overall survival (OS). ResultsEighteen studies with 1,887 patients met the inclusion criteria. The use of anti-PD1 antibody monotherapy as second-line treatment of RM-NPC revealed an ORR of 23 % (95 % CI = 19 %-28 %) and DCR of 51 % (95 % CI = 42 %-60 %). The ORRs for first-line as well as a combination of first and second-line treatments were 21 % (95 % CI = 15 % − 30 %) and 22 % (95 % CI = 6 % − 56 %, I2 = 75 %) respectively. The 12-month PFS and 12-month OS was also 27 % (95 % CI = 21 %–33 %) and 63 % (95 % CI = 53 %-72 %) respectively. ORR was much higher at 73 % (95 % CI = 32 %-94 %) when anti-PD1 antibodies were combined with Gemcitabine plus Cisplatin. ConclusionAnti-PD1 antibody demonstrate considerable activity in previously treated RM-NPC patients. Combining anti-PD1 antibodies with gemcitabine and cisplatin chemotherapy enhanced the efficacy of treatment.

220O RATIONALE-309: Effects of tislelizumab on health-related quality of life (HRQoL) in patients with recurrent or metastatic nasopharyngeal cancer (R/M NPC)

In RATIONALE-309 (NCT03924986), tislelizumab with gemcitabine and cisplatin (GP) improved progression-free survival, objective response rate, and duration of response compared to placebo +GP in patients receiving first-line treatment for R/M NPC. This study evaluated HRQoL in the intent-to-treat (ITT) population and post-hoc analysis examined HRQoL in patients with liver metastases (LM) subgroup, a negative prognostic factor of overall and cancer-specific survival in patients with NPC.

Antitumor activity of bintrafusp alfa in previously treated patients with recurrent or metastatic nasopharyngeal cancer (NPC): A single arm, prospective phase II trial.

e18029 Background: Patients with recurrent or metastatic nasopharyngeal cancer (R/M NPC) who failed platinum-based chemotherapy have poor prognoses. We report the clinical activity and safety of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor (TGF)-βRII receptor fused to a human IgG1 antibody blocking programmed death-ligand 1 (PD-L1), in patients with heavily pretreated R/M NPC. Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Methods: Eligible patients had histologically confirmed NPC that had recurred at distant sites and were not amenable to curative treatment. All patients received at least one prior line of platinum-based chemotherapy for recurrent disease. Patients were treated with bintrafusp alfa (1200mg every 2 weeks) until disease progression. The sample size was estimated to assume a 40% objective response rate (ORR) to bintrafusp alfa compared with 20% for checkpoint inhibitors. Modified Simon two-stage optimal design was used (power, 80%; a = 0.05; P0 = 0.20; P1 = 0.40; n1 = 18; n = 33 with an additional five patients to allow for ineligibility or other reasons). The primary endpoint was ORR and secondary endpoints included survival and toxicity. Expression of PD-L1 in archived tumors, plasma clearance of Epstein-Barr virus (EBV) DNA, plasma clearance of TGF-β, and exosomal PD-L1 were assessed for a potential correlation with ORR. (NCT 04396886). Results: Out of 43 patients screened, 38 patients were enrolled. After a median follow-up of 14.9 months (range: 1.6-23.3 months), the confirmed ORR was 23.7% (95% CI: 12.4-38.8%) (complete response, n = 1; partial response, n = 8). The median treatment duration was 1.8 months (range: 0.5-14.3 months). 8 patients (21.1%) and 2 patients (5.3%) received bintrafusp alfa for &gt; 6 months and &gt; 12 months respectively. The 1-year overall survival (OS) rate was 57.5% (95% CI, 40.2% to 71.5%) and 1-year progression-free survival rate was 23% (95% CI, 10.1% to 39.4%). ORR was higher in patients with a decreasing trend in EBV-DNA at week 4 (40% vs. 6.3%, p = 0.02), whereas high exosomal PD-L1 levels at week 4 were predictive of worse ORR (5.3% vs. 41.7%, p = 0.012). There were no associations between clinical outcome and tissue PD-L1 expression (p = 0.952) or plasma TGF-β clearance (p = 0.28). 16 patients (42.4%) experienced ≥ grade 3 treatment-related adverse events, most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). Conclusions: Bintrafusp alfa has promising activity in heavily pretreated R/M NPC and a favorable 1-year OS rate, though the observed activity was not as high as the study initially aimed. The biomarker results warrant validation in larger cohorts. Clinical trial information: NCT04396886.

Capecitabine Monotherapy as Palliative Treatment for Patients with Recurrent/Metastatic Nasopharyngeal Cancer.

Background Numerous chemotherapeutic agents have antitumor activity in recurrent/metastatic (R/M) nasopharyngeal cancer (NPC). Evidence of capecitabine's effectiveness as monotherapy is limited. Capecitabine tolerability in solid malignancies has ethnic and geographical variability. We investigated capecitabine's tolerability and identified potential prognostic factors for clinical outcomes in R/M NPC. Methods A consecutive retrospective cohort of patients who received capecitabine as the first recurrence, second- or third-line monotherapy for metastatic NPC (2011–2019) was reviewed concerning patient characteristics, pathological features, treatment outcomes, and toxicity. Results Fifty-one patients were eligible (median age at diagnosis: 42 [35.5–52.5] years). Most patients (78.4%) tolerated a standard oral dose of 1,250 mg/m2 capecitabine (2 weeks on/1 week off) in a 3-week cycle. The objective response rate was 49%, and the disease control rate was 66.7%, with a median response duration of 6.2 months. Hand-foot syndrome (HFS) was associated with a higher objective response rate (odds ratio, 5.1 [95% confidence interval: 1.18–21.98]; P = 0.02). The median follow-up duration was 17.8 (interquartile range: 7.8–30.4) months. The median (95% confidence interval) progression-free survival and overall survival were 6.6 (4.3–8.8) and 32.7 (25.9–39.5) months, respectively. HFS (P = 0.02), better performance status (P = 0.02), and absence of brain metastasis (P = 0.04) were associated with prolonged progression-free survival. Conclusion Capecitabine monotherapy is effective and well-tolerated as a palliative treatment for R/M NPC. Despite the lower incidence of HFS in our patients, it remained a favorable prognostic factor for objective response and progression-free survival.

163P Health-related quality of life (HRQoL) with pembrolizumab (pembro) vs chemotherapy (chemo) in platinum-pretreated recurrent or metastatic (R/M) nasopharyngeal cancer (NPC): Phase III KEYNOTE-122 study

Pembro did not improve OS vs chemo in patients (pts) with platinum-pretreated R/M NPC in KEYNOTE-122 (NCT02611960), but it had manageable safety and fewer treatment-related AEs. HRQoL results are shown.

Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy

Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding 68Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.

Role of Primary and Metastasis Directed Radiotherapy in Metastatic Nasopharyngeal Cancer

Role of Primary and Metastasis Directed Radiotherapy in Metastatic Nasopharyngeal Cancer

Combination Treatment With Paclitaxel, Carboplatin, and Cetuximab (PCE) as First-Line Treatment in Patients With Recurrent and/or Metastatic Nasopharyngeal Carcinoma.

Background: Platinum-containing doublet chemotherapy regimens are generally considered the standard first-line systemic therapy for recurrent or metastatic (R/M) nasopharyngeal cancer (NPC). Gemcitabine (GEM) plus cisplatin (CDDP) has become a standard therapy based on a phase 3 study in several countries, yet this regimen sometimes affects quality of life due to nausea or appetite loss. Here, we present the manageable toxicity and promising activity of paclitaxel + carboplatin + cetuximab (PCE) therapy for R/M NPC.Materials and Methods: We conducted a retrospective review of patients with R/M NPC who were treated with PCE from 2013 to 2019 at the National Cancer Center East, Kashiwa, Japan. PCE consisted of PTX 100 mg/m2 on days 1 and 8; CBDCA area under the blood concentration–time curve (AUC) 2.5 on days 1 and 8, repeated every 3 weeks; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly, as reported in the paper.Results: Fourteen patients were identified, consisting of 10 males and 4 females with a median age 59.6 years (range, 43–74). Among the 12 of 14 patients assessed for efficacy, overall response rate was 58.3%, with 2 complete responses and 5 partial responses. On median follow-up of 23.8 months, median overall survival was not reached with observed death events of 2. Median PFS was 4.1 months (95% CI, 2.6–5.6 months). Two patients experienced disease progression during cetuximab maintenance and restarted PCE treatment, then achieved partial response again. The most common grade 3 or 4 adverse events were neutropenia (21.4%) and skin reaction (14.3%). No treatment-related death was observed.Conclusion: Although the number of study population was small, our results suggest that PCE is feasible and potentially effective for R/M NPC, with a 58.3% response rate and 4.1-month PFS. Further prospective evaluation is warranted.

Clinical response and biomarker analysis of POLARIS-02 a phase II study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) in patients with metastatic nasopharyngeal carcinoma.

6542 Background: Metastatic nasopharyngeal cancer (mNPC) patients progressed after standard therapy have limited treatment options. This study is to evaluate the clinical efficacy and safety of toripalimab in mNPC patients refractory to standard chemotherapy treatment (Clinical trial ID: NCT02915432). Methods: Patients receive 3 mg/kg toripalimab Q2W via IV infusion until disease progression, unacceptable toxicity, or voluntary withdrawal. Clinical response is assessed every 8 weeks according to RECIST v1.1. Tumor PD-L1 expression, plasma EBV titer and other biomarkers will be evaluated for correlation with clinical response. Results: From Dec 2016 to Feb 2019, 190 mNPC patients were enrolled from 17 participating centers in China. The median age was 46 years with 83% male. Patients were heavily pretreated with a median of 2 lines of prior systemic treatments. By the cutoff date of Jan 17, 2020, 97% patients experienced treatment related adverse events (TRAE). Most common TRAE included anemia, hypothyroidism, AST increased, proteinuria and fever. Grade 3+ TRAE occurred in 28% patients. Among 190 patients assessed by Independent Review Committee per RECIST v1.1, 6 CR, 33 PR and 40 SD were observed for an ORR of 20.5% and a DCR of 41.6%. The median DOR was 12.9 months. The median PFS and median OS were 1.9 months and 18.6 months respectively. PD-L1+ patients (n=48) had higher ORR than PD-L1- patients (n=134), 27.1% versus 19.4%. By tumor histology, ORR was higher in keratinizing NPC (n=8) than non-keratinizing NPC (n=168), 62.5% versus 19.0%. 144 patients had valid plasma EBV titer measured every 28 days during the study. An average drop of 101-fold plasma EBV titer from baseline was observed in patients with objective responses. Patients with 2-fold+ drop in plasma EBV titer on day 28 (n=60) went on to have 48.3% ORR and 76.7% DCR, whereas patients with less than 2-fold drop (n=88) had 5.7% ORR and 25.0% DCR. 14 responding patients who later developed progressive disease had at least 2-fold+ increase of plasma EBV tier 3-months (median) before radiographic identification of disease progression. Conclusions: Toripalimab demonstrated encouraging clinical activity with a manageable safety profile in mNPC patients refractory to standard chemotherapy. Patients with 2-fold+ drops in plasma EBV titer on day 28 from baseline had favorable clinical response of 48.3% ORR, which might be used as a predictive biomarker. Clinical trial information: NCT02915432 .