Background

Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer, with a median disease-free survival (DFS) of less than 3 years. SDC is androgen receptor-positive (AR+) in 67-96% of cases. In incurable recurrent AR+ SDC androgen deprivation therapy (ADT) has an overall response rate of 18-50%. In this study, high-risk AR+ SDC pts were treated with adjuvant ADT to study the efficacy.

Methods

In this retrospective study, surgical resected pts who received adjuvant ADT for stage 4a/b AR+ SDC at the Radboudumc (Nijmegen, the Netherlands) or Istituto Nazionale dei Tumori (Milan, Italy) were collected. As control group, surgical resected pts diagnosed with stage 4a/b SDC between 1990-2014, who did not receive adjuvant ADT were collected by a search of the Dutch pathology database (PALGA). Pts were analyzed for DFS and overall survival (OS) by using Kaplan-Meier survival curves.

Results

18 AR+ SDC pts (median age 64 years [range 32-80]) were treated with adjuvant ADT (Nijmegen n = 11; Milan n = 7) for a median duration of 10 months [range 2-31 months]. All pts had a nuclear AR-staining pattern in > 70% of the cells. They were treated with bicalutamide monotherapy (n = 10), a LHRH analog (n = 1) or a combination of these (n = 7). Treatment was well tolerated. 17/18 pts (94.4%) also received postoperative radiotherapy, of which 4 pts received concurrent chemoradiotherapy (22.2%). The control group consisted of 110 SDC pts (median age 70 years [range 44-100]). 103/110 pts (93.6%) received postoperative radiotherapy, of which 1 pt received concurrent chemoradiotherapy (0.9%). After a median follow-up of 22 months in the ADT-treated SDC pts and 25 months in the control SDC pts, the 3-year DFS was 53.6% and 34.2% (p = 0.137), the 3-year OS was 68.2% and 52.3% (p = 0.198), respectively. The median DFS and OS were not reached in the ADT-treated SDC pts and were 21 months and 46 months in the control SDC pts.

Conclusions

Adjuvant ADT in high-risk AR+ SDC pts did not lead to a significant increase in DFS or OS, but the number of treated pts was limited. Due to the rarity of the disease we could not perform a formal phase II study. Translational research to identify pts which may benefit from ADT is warranted.

Legal entity responsible for the study

Carla M.L. van Herpen

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer (SGC). Activation of the cellular MET (c-MET) receptor tyrosine kinase has been implicated in cell proliferation, survival, migration, and invasion. The aim of this study was to evaluate the frequency of MET overexpression and its correlation to clinicopathological factors in SDC.

Methods

136 patients were collected by a retrospective search of the Nationwide Network and Registry of Histo- and Cytopathology (PALGA) in the Netherlands. Formalin-fixed paraffin-embedded tumor blocks and hematoxylin and eosin stained slides were requested for pathological review. MET expression was evaluated by immunohistochemical staining on primary tumors. These data were correlated to clinicopathological factors.

Results

c-MET was positive in 54 of 136 tumors (39.7%). Of these 54 tumors, 50 had a cytoplasmic staining pattern and 23 had a membranous staining pattern, so in 19 tumors both cytoplasmic and membranous staining was observed. No correlations were found between cytoplasmic or membranous MET and high stage disease (stage 3 and 4 versus stage 1 and 2, p = 0.606 and p = 0.300 respectively), number of positive lymph nodes (p = 0.263 and p = 0.955 respectively), lymph node ratio (p = 0.192 and p = 0.771 respectively), androgen receptor-status (p = 0.858 and p = 0.258 respectively), HER2-status (p = 0.257 and p = 0.595 respectively), time to recurrence (p = 0.559 and p = 0.959 respectively), time to distant metastases (p = 0.398 and p = 0.666 respectively), or overall survival (p = 0.754 and p = 0.516 respectively). Membranous MET staining occurred more frequently in SDC ex pleomorphic adenoma (14 of 52 tumors) than in the ‘de novo’ SDC (9 of 84 tumors) (p = 0.014). In SDC ex pleomorphic adenoma we also found more HER2-positive tumors (p = 0.041).

Conclusions

Cytoplasmic and membranous MET are overexpressed in SDC and may be a target for MET-targeted therapy. It is not a prognostic factor for overall survival, possibly because frankly invasive SGCs often show less receptor expression then minimally invasive SGCs or pleomorphic adenomas. The higher expression of c-MET and HER-2 in SDC ex pleomorphic adenoma needs further investigation.

Legal entity responsible for the study

Carla M.L. van Herpen

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Recently, a new subtype of salivary gland cancer (SGC), mammary analogue secretory carcinoma (MASC), has been defined, which is characterized by the presence of ETV6-NTRK3 fusion gene. Previously, MASC was mixed up with acinic cell carcinoma (AciCC), polymorphous low grade adenocarcinoma and (cyst)adenocarcinoma. At present the clinical features and outcome of MASC patients are not well known. We aimed to describe the clinical presentation and outcome of MASC.

Methods

Firstly, we re-evaluated the pathological diagnosis of salivary gland cancers with a morphological resemblance to MASC, diagnosed in 4 of the 8 head and neck centres in the Netherlands, for their presence of ETV6-NTRK3 and also included genetically confirmed prospectively diagnosed cases. The ETV6-NTRK3 fusion gene was analyzed using RT-PCR. Secondly, the clinical characteristics were retrieved from the patient files.

Results

Twenty-eight patients with ETV6-NTRK3 fusion gene positive MASC were included (10 prospectively and 18 retrospectively). Of these 18 retrospective patients 13 patients were previously diagnosed as AciCC, the other 5 patients as (low-grade) adenocarcinoma. The median age at diagnosis was 49 years (range 19 – 83 years), 15 patients (54%) were male. The duration of symptoms varied from 6 weeks until 20 years with a median of 14 months. In 18 patients (64%) the tumour was located in the parotid gland; the other patients had tumours of the minor salivary glands (2), submandibular gland (1), oral mucosa/lip (5) or palate (2). All patients had a T1-2 tumour. One patient had lymph node metastasis at diagnosis. All patients underwent surgery of which 4 patients needed re-resection and 12 patients (43%) underwent postoperative radiotherapy. One patient had a local recurrence 50 months after primary surgery, but was cured after second resection. None of the patients had regional recurrences or distant metastases. The median follow-up was 49 months and both the 5- and 10-year overall survival rate were 94%.

Conclusions

MASC is a recently acknowledged new entity of SGC characterized by the ETV6-NTRK3 fusion gene. The clinical course seems to be favourable with a very low rate of recurrences and an excellent survival.

Clinical trial identification

Clinical trial identification not applicable

Legal entity responsible for the study

Radboudumc

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Immune checkpoint inhibitors used in the neoadjuvant setting may enhance systemic immunity to prevent tumor recurrence, and previous data suggest administration in the preoperative setting is safe. CheckMate 358 explored the safety and feasibility of neoadjuvant nivolumab in patients (pts) with resectable human papillomavirus (HPV)+ or HPV− SCCHN.

Methods

This cohort is part of an ongoing global, multicenter study of virus-associated cancers (CheckMate 358; NCT02488759). Pts were PD-L1–unselected with newly diagnosed, previously untreated, resectable, HPV+ or HPV− SCCHN of the oral cavity, pharynx, or larynx with T1 or greater primary lesions and N1 or greater nodal disease. Pts were to receive nivolumab 240 mg on days 1 and 15 and surgery on day 29 ± 7. Tumor assessments by CT scan occurred at screening, presurgery, and during follow-up. Pretreatment tumor biopsies, surgical specimens, and peripheral blood were collected. Primary endpoints were safety (incidence of TRAEs) and delay >4 weeks from planned surgical date due to TRAEs. Investigator-assessed change in tumor dimensions was an exploratory endpoint. Additional assessments include pathologic response, tumor PD-L1 expression, and immune correlates. Preliminary results from a Feb 2017 database lock are reported.

Results

Of 29 pts enrolled, 12 had HPV+ tumors and 17 HPV−. Median (range) follow-up was 22 (2–41) wks (HPV+) and 12 (4–56) wks (HPV−). All pts received both doses of nivolumab. Grade 3–4 TRAEs occurred in 2 (16.7%) pts with HPV+ tumors (lipase increased; glossodynia) and 2 (11.8%) pts with HPV− tumors (lipase increased); no new safety signals were identified. TRAEs did not result in any protocol-defined surgery delays. As of database lock, presurgery tumor reduction per CT scan was observed in 11 of 23 (48%) evaluable pts (5/10 HPV+ and 6/13 HPV−); 3 pts had tumor reduction ≥40% (largest reduction, 75%).

Conclusions

This is the first report of a global trial of neoadjuvant anti–PD-1 therapy in pts with both HPV+ and HPV− SCCHN. Nivolumab was well tolerated, with no surgery delay due to TRAEs. Nivolumab led to tumor reductions within 1 month in nearly half of evaluable pts.

Clinical trial identification

NCT02488759

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

R.L. Ferris: Other from Amgen, Astra-Zeneca/MedImmune, Bristol-Myers Squibb, EMD Serono, Lilly, Merck, Pfizer, VentiRx Pharmaceuticals, outside the submitted work. S.S. Baxi: Consulting fees from BMS, outside the submitted work. U.M. Martens: Personal fees from Bristol-Myers Squibb, Roche, EMD Serono, Amgen, outside the submitted work. W.C. Spanos: Personal fees from BMS, Merck, outside the submitted work. R.S. Leidner: Research support from BMS, MedImmune/AstraZeneca. H. Kang: Grants and non-financial support (to institution) from BMS, during the conduct of the study; grants from Merck, Novartis, Plexxikon, Advaxis, Immunogen, VentiRx Pharmaceuticals, AstraZeneca, outside the submitted work (to institution). J. Russell: Consulting for EMD Serono. I. Soumaoro, S. Rao, Z.A. Cao: Employee of Bristol-Myers Squibb. S. Topalian: Grants and non-financial support from BMS; personal fees from Amgen, MedImmune/AstraZeneca, Merck, Pfizer, AbbVie; Personal fees & other from Five Prime Therapeutics, Jounce Therapeutics; Grants, personal fees & other from Potenza Therapeutics. All other authors have declared no conflicts of interest.

Background

Clinically meaningful antitumour activity and improved overall survival (OS) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) have been achieved by targeting the PD-1/PD-L1 axis. Tumoral PD-L1 expression correlates with response to blocking PD-1/PD-L1 antibodies. In a retrospective study, we investigated tumoral PD-L1 expression as a prognostic biomarker in R/M HNSCC patients (pts) treated with standard of care (SOC) therapy.

Methods

Archival tumor samples from R/M HNSCC pts diagnosed between March 2011 and June 2015 at 19 institutions in 7 countries were evaluated for PD-L1 expression using the validated Ventana SP263 assay and scored as PD-L1 high (≥25% of tumor cells [TC]) or low/negative (<25% of TC). Clinical-demographic data, including treatment patterns and outcomes, were extracted from medical records. Descriptive analyses were conducted and survival estimated by the Kaplan-Meier method. Progression-free survival (PFS) was defined from start of first- (1L) or second-line (2L) therapy to time of progression (on/after therapy) or death due to any cause. OS was defined from diagnosis index date of R/M disease to time of death. The Cox proportional hazards model was applied.

Results

The final dataset included 412 pts. Median age was 62.0 years (range 28.0–93.0); 79.9% were male and 88.2% white. PD-L1 expression was high in 132 (32.0%), low/negative in 264 (64.1%), unknown in 16 (3.9%). Median OS (8.2 vs 10.1 months; P = 0.55) and PFS from the start of 1L chemotherapy (4.2 vs 4.8 months; P = 0.37) did not significantly differ between PD-L1 high and low/negative pts, respectively. Median PFS following 2L chemotherapy was statistically significantly longer in PD-L1 high versus low/negative pts (4.1 vs 2.2 months; P = 0.04). PD-L1 status was not statistically significant in multivariate analyses of OS (P = 0.74) or PFS following 1L chemotherapy (P = 0.63); however, there was a trend for improved PFS following 2L chemotherapy (P = 0.09).

Conclusions

Tumoral PD-L1 expression was not significantly associated with OS or PFS following 1L SOC chemotherapy; however, it was associated with prolonged PFS following 2L SOC chemotherapy.

Clinical trial identification

NCT02543476 (August 25, 2015)

Legal entity responsible for the study

AstraZeneca PLC

Funding

AstraZeneca PLC

Disclosure

S. Pai: Corporate sponsored research (Abbvie, AstraZeneca, Oncosec, Tesaro), Consultant (Abbvie, AstraZeneca, Merck, Oncosec) Investigator-initiated studies (AstraZeneca, Merck) Speaker at IO drug launches for HN cancer in an international country (Merck). E.E. Cohen: Consultant (Eisai; Pfizer; Merck; AstraZeneca; Bristol-Myers Squibb; Human Longevity(HLI)). D. Lin: Corporate sponsored research (Abbvie, Tesaro, AstraZaneca). G. Fountzilas: Consultant (Pfizer, Sanofi, Roche) Stock shareholder (ARIAD (an immediate family member)) Honoraria (AstraZeneca). E.S. Kim: Consultant (Celgene, Boehringer Ingelheim, Eli Lilly, AstraZeneca). N. Baste: Corporate sponsored research (AstraZeneca) Consultant (Bristol-Myers Squibb, MSD, Merck Serono) D. Clayburgh: Corporate sponsored research (Abbvie & AstraZeneca. N. Shara: Honoraria (NIH-reviewer) Full-time/part-time employee (MedStar Health Research Institute) J. Zhang: Consultant (AztraZeneca & Boehringer Ingelheim). M. Stokes: Employment (Evidera) and research funding (Evidera). D. Lawrence: Full time employee of AstraZeneca UK. A. Khaliq, G. Melillo, N. Shire: Employee and Shareholder (AstraZeneca). All other authors have declared no conflicts of interest.

Background

Programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) are up-regulated in many cancers. The purpose of this study was to explore the relationship between PD-L1 expression and overall survival (OS) in HNSCC.

Methods

A retrospective study was conducted using data from pt medical records and analysis of archival tumor samples. Sample ages ranged from 8.2 to 227.5 months. Pts ≥18 years old diagnosed with HNSCC between 1989 and 2015 were selected. Demographic and tumor characteristics were compared by PD-L1 expression status. PD-L1 testing was performed using the Ventana PD-L1 SP263 assay. PD-L1 expression was scored separately using tumor cell (TC) and immune cell (IC) membrane staining and exploratory cut-offs of 1%, 5%, 10%, 25% and 50%. OS was calculated as the number of months from initial HNSCC diagnosis until death and estimated using the Kaplan–Meier method. The log-rank test was used to compare survival curves by PD-L1 status. PD-L1 status as a prognostic indicator of OS was further examined in Cox proportional hazards (PH) models.

Results

We identified 214 HNSCC pts with data available for date of death/last follow-up and PD-L1 status. Mean (SD) tumor sample age was 93.3 (40.5) months. Mean (SD) pt age was 62.3 (13.4) years and 70% were male. The Table presents baseline characteristics by PD-L1 subgroup. Median OS was similar between PD-L1 high and low/negative pts classified using the TC ≥ 25%, IC ≥ 1%, and IC ≥ 25% cut-offs. However, median OS was 21.2 months longer in PD-L1 high versus low/negative pts (68.9 vs. 47.7 months, respectively; P=0.03) in analyses using the TC ≥ 1% cut-off. This latter relationship remained after adjusting for baseline covariates using Cox PH models.Table:

1049PD Baseline characteristics

Conclusions

PD-L1 high expression based on a TC ≥ 1% cut-off appears to be associated with improved OS in this sample of pts with HNSCC. A small number of samples and resulting low statistical power limited our ability to assess prognosis for TC ≥ 25% and IC ≥ 25%, yet OS was numerically higher among PD-L1 high pts in these subgroups.

Clinical trial identification

NA

Legal entity responsible for the study

AstraZeneca

Funding

AstraZeneca

Disclosure

M. Stokes: Employment (Evidera) and research funding (Evidera). R. Wang: Employment (Evidera) and Stock ownership (Evidera). S. Wildsmith, H.K. Angell, C. Barker, J. Walker, P. Scorer, N. Shire: Employment (AstraZeneca) and Shareholder (AstraZeneca). M. Secrier: Employment (AstraZeneca) Corporate sponsored research (AstraZeneca) and Shareholder (AstraZeneca). M.C. Rebelatto: Employment (AstraZeneca/MedImmune) and Shareholder (AstraZeneca/MedImmune).

Background

Cisplatin (Cis), continuous infusion 5FU and Cetuximab (Cet) (EXTREME) first-line treatment extends overall survival (OS) over Cis and 5FU of recurrent/metastatic squamous cell head and neck cancer (RM SCCHN) patients. In EXTREME, Cet has been added to a 2-drug combination, which has never shown superiority over any single drug. In this scenario, we are left with an open question about the significance of adding 1 or 2 drugs to biotherapy. In addition, a significant number of pts are excluded from EXTREME for the high incidence of ≥ G3 adverse events (AEs) (>80%), most of them attributable to 5FU. Paclitaxel (P) is active and safe, both alone and with Cis. We conducted a phase IIb trial comparing a 2-drug Cet-Cis regimen with a 3-drug combination (substituting 5FU with P) in terms of progression-free survival (PFS) and tolerability.

Methods

Eligible pts had confirmed untreated R/M SCCHN. Pts were randomized to a 3 vs. a 2-drug combination (Cet + Cis w/o P) with maintenance Cet after 6 cycles. Primary endpoint was PFS; secondary end-points were overall survival (OS), response rate (RR) and toxicity. We assumed a non-inferiority margin of 1.40 as compatible with efficacy.

Results

200 pts were randomized and 191 evaluable. Pt characteristics were balanced in the 2 arms. Inferiority hypothesis was rejected (upper limit of one-sided 90% CI of PFS hazard ratio<1.4). Median PFS was 6 and 7 mos (95% CI: 5-7 and 6-8 mos) in the 2 vs. 3-drug arms, respectively (p=NS), median OS was 13 and 11 mos (95% CI: 10-16 and 9-14 mos) (p=NS), and RR was 42% vs 52% (p=NS). Grade ≥ 3 AEs were 76% and 73% for the 2 vs 3-drug regimen, respectively. Skin rash and electrolyte alterations were mainly reported in the 2-drug arm, while haematological toxicities and infections in the 3-drug arm. No toxic death and sepsis were reported and cardiac events were negligible (1%).

Conclusions

A 2-drug Cet and Cis regimen proved to be non-inferior in PFS to a 3-drug combination with Cet, Cis and P. The median OS of both regimens is comparable with the 10.1 mos in EXTREME, while life-threatening toxicity rate appeared reduced. These regimens warrant further investigation as a backbone to immunotherapeutic agents.

Clinical trial identification

EudraCT: 2011-002564-24

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale Tumori Milano

Funding

Merck Serono

Disclosure

All authors have declared no conflicts of interest.

Background

About 47% and 10% of head and neck squamous cell carcinomas (HNSCC) occur in patients (pts) aged 65+ or 80+ respectively. This population being heterogeneous, balancing efficacy with toxicity is challenging.

Methods

ONCOVAL is the first step of the ELAN program for pts 70+ with HNSCC, not amenable to surgery. During ONCOVAL, pts were assessed for frailty before inclusion to appropriate trial depending on curative or palliative setting and fit or unfit status. The primary aim was to evaluate whether a suited geriatric evaluation (SGE) for use by oncologist is feasible to stratify pts as fit or unfit. The SGE was elaborated by GERICO (French UNICANCER group dedicated to clinical research in elderly cancer pts) specifically for HNSCC pts, derived from the comprehensive geriatric assessment (CGA) and evaluating functional status, comorbidity, cognition, mental health status, social status, nutrition. Full CGA performed by geriatricians was optional.

Results

Between 06/2013 and 02/2017, 495 pts were included in 42 centers. Data available for 463 pts. Median age 79 years (70-95) with 46% over 80. 74% males. 67% of SGE was performed by oncologists and 33% by nurses/clinical research staff. Mean time to complete SGE was 22 minutes. After SGE, 72% pts were classified as unfit. 52% of pts were further assessed by CGA, 48% among SGE fit pts and 53% among SGE unfit pts. Concordance rate of classification Unfit/Fit by SGE and CGA was 81%. Among pts planned to be treated by curative radiotherapy (RT) or chemo(CT)-RT after oncologic evaluation alone, the planned treatment changed after SGE for 8% of pts: addition of CT/biotherapy to RT for 4% or deletion of CT for 4%. Rate of pts requiring multidisciplinary interventions was significantly higher when the assessment was also performed by geriatricians (71% vs 51%), even after adjusting for frailty.

Conclusions

A CGA-based SGE for use by oncologist in older pts with HNSCC seems feasible and is a first necessary step to define optimal care. Oncologists and geriatricians must keep going developing such close collaboration and data sharing before proposing tailored treatment.

Legal entity responsible for the study

Gustave Roussy

Funding

INCa (National Institut of Cancer), ARC, Ligue Nationale Contre le Cancer

Disclosure

H. Le Caer: Grant/: research: Roche. C. Even: Advisory/Board Member: Bristol-Myers Squibb, AstraZeneca, Merck Serrono, MSD, Innate Pharma. F. Peyrade: Advisory board: Board ORL Merck France. Y. Pointreau: Advisory/Board Member: Bristol-Myers Squibb; Honoraria: Bristol-Myers Squibb, MSD. P. Debourdeau: Advisory/Board Member: Pfizer. J. Fayette: Advisory/Board Member: Bristol-Myers Squibb, Honoraria: Bristol-Myers Squibb, AstraZeneca. R. Boulahssass: Advisory/Board Member: Teva Honoraria: Nutricia, Roche, Teva, Novartis, Pierre Fabre, Amgen, takeda, Kephren. J. Guigay: Advisory board: AstraZeneca; Bristol-Myers Squib, Innate Pharma, Merck serono Grant/: research: Bristol-Myers Squibb, Chugai, Gsk, Merck Serono. All other authors have declared no conflicts of interest.

Background

Patients with recurrent head and neck squamous cell cancer (rHNSCC) have a poor prognosis once they have failed definitive treatment. We have completed a Phase 1 dose-escalation study of a unique targeted light activated drug conjugate RM1929 consisting of the EGFR-directed monoclonal antibody cetuximab conjugated to the phthalocyanine dye IRDye 700DX.

Methods

This was a Phase I study of rHNSCC patients who could not be satisfactorily treated with surgery, radiation, or platinum chemotherapy. The study included a drug dose-escalation with a fixed fluence light application to determine the drug dose that could be safely given to activate the pharmacodynamics of anticancer responses. Twenty-four hours after drug infusion non-thermal red light was applied to the tumors either on the surface for mucosal/skin disease or within the tumor via fiber optic diffusers for submucosal or nodal disease. Primary safety endpoints were assessed at 1 week and secondary efficacy endpoints were assessed at 1 month post treatment.

Results

Nine patients were enrolled in the 3 cohort dose escalation study. There were no dose-limiting toxicities and the drug dose and light fluence for treatment was determined. No photosensitivity reactions were observed at any drug dose during solar simulator testing. Four patients experienced 3 SAEs that were probably or possibly related to treatment including oral pain, tumor hemorrhage, and tumor pain. For 8 patients who were assessed for best overall response rate after a single cycle of treatment using clinical and RECIST 1.1, the objective response rate (ORR) was 75% (6/8) with 3 complete responses which were durable (4-16 months). The disease control rate was 100% (DCR). 7/8 patients showed a decrease in tumor density, consistent with post-treatment necrosis.

Conclusions

The phase 1 dose escalation study demonstrated the safety and tolerability of photoimmunotherapy with RM1929. We have observed improvement in clinically significant endpoints in patients with rHNSCC who do not have other treatment options.

Clinical trial identification

NCT02422979

Legal entity responsible for the study

FDA

Funding

Aspyrian Therapeutics

Disclosure

All authors have declared no conflicts of interest.

Background

This trial was conducted to investigate the efficacy and safety of paclitaxel plus carboplatin with/without bevacizumab in recurrent or metastatic nasopharyngeal carcinoma (NPC).

Methods

Patients with recurrent or metastatic NPC recruited from 12 hospitals in China were randomly assigned to receive carboplatin (area under the curve 6) and paclitaxel (175 mg/m²) intravenously on day 1 once per 3 weeks for a maximum of 6 cycles, with (CP+B) or without (CP) bevacizumab (7.5 mg/kg) intravenously on day 1 of each cycle, until disease progression, untolerable toxicity, or death. The primary endpoint was progression-free survival (PFS). Secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. This study is ongoing and registered with ClinicalTrials.gov (NCT02250599).

Results

Between Jun 8, 2015 and Jan 1, 2017, 80 patients were randomly assigned, 41 to the CP+B group and 39 to the CP group. ORR showed a numerical improvement with CP+B group (85.4% vs 69.2%) although with no statistical difference (p = 0.084). The median PFS was 7.23 months in the CP+B group and 7.00 months in the CP group (p = 0.506). OS had not yet matured. Safety was similar in two groups. No bevacizumab related serious adverse events were observed specially including bleeding.Table:

1052PD

Conclusions

CP+B regimen showed a numerical advantage in ORR among NPC patients. Given the limited sample size of our study, further research is needed to evaluate efficacy of bevacizumab in NPC.

Clinical trial identification

NCT02250599 Protocol Registration Receipt: 09/26/2014

Legal entity responsible for the study

the Institutional Review Board and academic committee of Sun Yat-Sen University Cancer Center

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

We incorporated baseline plasma EBV DNA into refinement of stage groups for nasopharyngeal carcinoma (NPC) treated with radical intensity-modulated radiation therapy (IMRT).

Methods

Patients with non-metastatic NPC treated with radical IMRT +/- adjunct chemotherapy based on 7^th edition of American Joint Committee on Cancer (AJCC) system were recruited prospectively from 2010 to 2016. All patients had baseline and serial post-IMRT plasma EBV DNA (in copies/ml) measured and were staged with MRI and PET-CT. Recursive partitioning analysis (RPA) with repeated internal validations derived new stage groups with incorporation of baseline plasma EBV DNA. Multivariable analyses were used to calculate adjusted hazard ratios (AHRs) to derive a new set of AHR stages. Comparison of performance of survival prediction among these 3 sets of stage groups was done to find the best-performing stage set.

Results

The cohort included 520 patients treated with IMRT +/- adjunct chemotherapy with a median follow-up of 5.0 years. They were re-staged based on 8^th edition of AJCC system. 5-year overall survival (OS) and cancer-specific survival (CSS) were as follows: stage I (OS 89.5%; CSS 100%), II (OS 87.8%; CSS 94.7%), III (OS 85.0%; CSS 90.0%) and IVA (OS 74.4%; CSS 79.9%) (p = 0.058 and p = 0.003 respectively). RPA derived NPC into 3 new stages with corresponding OS and CSS: RPA-I (T1-T4N0-N2 & T1-T2N3 & EBV DNA < =2000) (OS 89.1%; CSS 95.2%), RPA-II (T1-T4N0-N2 & T1-T2N3 & EBV DNA >2000) (OS 80.5%; CSS 84.1%) and RPA-III (T3-T4N3) (OS 58.2%; CSS 67.1%) (both p < 0.001 and p < 0.001 respectively). AHR (I: T1-T2N0-N2; II: T3-T4N0-N2 & T1-T2N3; III: T3-T4N3) after adjusting age, smoking status, treatment (chemoradiation vs. IMRT alone), baseline LDH and plasma EBV DNA also yielded a valid classification (p < 0.001 for both OS and CSS) but was worse on survival prediction compared to RPA. The RPA stages demonstrated better survival prediction especially on CSS after 1000 bootstrapping replicates (bootstrap scores – OS: 0.469; CSS: 0.752) than AHR stages (OS: 0.436; CSS: 0.206) and 8^th edition AJCC (OS: 0.095; CSS: 0.043).

Conclusions

A novel RPA-based TNM stage groups revealed significantly better survival prediction compared with the 8^th edition AJCC and AHR stages.

Clinical trial identification

NCT02476669

Legal entity responsible for the study

Department of Clinical Oncology, The University of Hong Kong and Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital

Funding

SK Yee Medical Foundation

Disclosure

All authors have declared no conflicts of interest.

Background

This study is to develop and validate a new classification for nasopharyngeal carcinoma (NPC).

Methods

Fifteen hundred and twenty-eight (1528) newly diagnosed NPC patients treated between 1995 and 2010 were included in this study. Seven hundred and one patients (n = 701) were treated with 3D conformal radiotherapy (3D-RT) and 827 patients were treated with IMRT. Cox proportional hazards model was used to select the significant split node to partition patients into the different risk group. Recursive partitioning analysis derived a new classification in patients treated with 3D-RT objectively. This new staging system was then validated in patients treated with IMRT.

Results

The median follow-up interval was 84.6 months (ranging 2-175 months). According to the 7^th AJCC staging system, the stage I patients showed a 5-year overall survival (OS) rate of 93.0%, stage II of 94.5%, stage III of 87.5%, stage IVA of 71.5%, stage IVB of 61.3%, and stage IVC of 5.8% (p < 0.0001). In the validation group (n = 827), the Group I in new system was patients with stages of T1-3N0-1 and T1N2 (n = 364); their 5-year OS was 92.4%. The Group II was patients with stages of T2N2 and T3N2 (n = 175); thier 5-year OS was 86.0%. The Group III was patients with stages of any T4 and N3 (n = 249); their 5-year OS was 72.0%. The Group IV was patients with distant metastasis (n = 36); their 5-year OS was 17.9%. This new classification system will be compared to the 8^th AJCC staging system.

Conclusions

We propose a new staging system for NPC, which distributes more patients in the early stage.Table:

1054PD Patient Distribution According to Chinese 2008 and the 7th AJCC staging systems

Clinical trial identification

Not applicable

Legal entity responsible for the study

None

Funding

Koo Foundation Sun Yat-Sen Cancer Center

Disclosure

All authors have declared no conflicts of interest.