Background

The benefit of adjuvant CT in NPC is controversial. We conducted a biomarker guided RCT using post-RT EBV DNA to select high risk NPC pts for adjuvant CT while sparing low risk pts from unnecessary toxicity.

Methods

Eligible NPC pts of AJCC (6^th Ed) stage IIB-IVB, ECOG 0-1, adequate organ functions, no locoregional disease or distant metastasis after RT/CRT, were screened for plasma EBV DNA at 6-8 weeks post-RT. Pts with EBV DNA =0 (copies/ml) were observed. Pts with EBV DNA >0 underwent work-up and were randomized to arm A (adjuvant cisplatin-gemcitabine x 6 cycles) or arm B (observation). Primary endpoint for the RCT was relapse free survival (RFS). With a hazard ratio (HR) of 2, 100 randomized pts were required for a power of 0.8 and an alpha at 0.05.

Results

From 9/2006 to 7/2015, 789 pts were screened by plasma EBV DNA: 573 (72.6%) pts had EBV DNA =0, 216 (27.4%) pts had EBV DNA >0, 104 (13.2%) pts were randomized (arm A: 52; arm B: 52). The clinical characteristics and significant biomarkers (post-RT EBV DNA levels: 1-49/50-499/>=500; PET-CT scan: negative/positive) were evenly balanced in the two arms. After median follow up of 6.6 years (yr), there was no significant difference in RFS or overall survival (OS) between the two arms in the intent-to-treat and per protocol population, and by subgroup analysis defined by EBV DNA level and PET-CT. By recursive partitioning analysis (RPA), we identified three prognostic groups among 789 post-RT NPC pts (Table). The low risk group (EBV DNA < 50 and stage II/III) shared the same survival (5-ys OS 89%) as stage II but included more than twice the number of pts.Table: 336O

Conclusions

Adjuvant CT with cisplatin-gemcitabine did not improve survival in high risk NPC pts with detectable post-RT plasma EBV DNA. The low risk group (includes 66% of pts) can potentially be spared the toxicity of adjuvant CT.

Clinical trial identification

NCT00370890

Legal entity responsible for the study

Comprehensive Cancer Trials Unit, Department of Clinical Oncology, The Chinese University of Hong Kong

Funding

Support by central research funds from Hong Kong Hospital Authority and The Chinese University of Hong Kong. Gemcitabine provided by Eli Lilly.

Disclosure

E.P. Hui: Advisory Board: MSD, BMS; Speaker Honorarium: MSD. A.T.C. Chan: Research funding: Pfizer, Boehringer Ingelheim, BMS, MSD Travel, accomodation and expenses: Roche, Pfizer, Novartis, BMS. R.K.C. Ngan: Travel, accomodation and expenses: Eisai, Merck, Pfizer, Roche, Novartis. V.H. Lee: Honorarium: Roche, Eli Lilly, Pfizer. B.C. Zee: Patent, royalties: Health View Bioanalytics. K.C.A. Chan: Patents, royalties, other intellectual property: Sequenom, Illumina, Xcelom, Cirina. Stock or other ownership: Cirina, Xcelom. Honoraria, travel, accomodations, expenses: Biorad. Consulting or advisory role: Xcelom.

All other authors have declared no conflicts of interest.

Background

Identifying germline BRCA mutations in ovarian cancer patients is important for the medical management of patients and risk management for relatives. In Asia, genetic services are relatively inaccessible mainly due to the lack of genetic counselling. Mainstreaming improved access to cancer genetic testing in United Kingdom, hence its feasibility is being tested in Malaysia. The MaGiC Study aims to (a) determine the prevalence of germline BRCA1/BRCA2 mutations in a population-based cohort (b) determine the feasibility of mainstreaming genetic counselling and testing and (c) investigate the psychosocial impact of genetic testing in Malaysia

Methods

This is a prospective observational study of 800 patients with non-mucinous ovarian cancer irrespective of family history, recruited via a mainstreaming pathway where patients are counselled by non-genetic clinicians or the traditional genetics pathway. Phone interviews are conducted after pre-test counselling and result disclosure to study feasibility and psychosocial impact using Genetic Counselling Satisfaction Scale (GCSS), Decisional Conflict Scale (DCS), Psychosocial Aspect of Hereditary Cancer (PAHC) and Cancer Worry Scale (CWS).

Results

70 clinicians from 29 sites nationwide recruited 248 patients. 208 patients were tested. 27 (13%) pathogenic mutations, 33 (16%) variants of uncertain significance and 148 (71%) negatives were identified. Analysis of 160 patients showed that GCSS, DCS, PAHC and CWS were reliable. Most patients were satisfied with their counselling experience, not conflicted in making decision, felt informed about their choices. PAHC showed that 79% patients at pre-test and 69% at post test had a problem mainly on ‘living with cancer’. Distress Thermometer showed 41 of 158 (26%) patients may require psychosocial support at pre-test but reduced to 17% after result disclosure. For CWS, 64 of 156 (41%) patients at pre and 26 of 64 (41%) at post-test reported to have frequent concerns about getting cancer again.

Conclusions

Mainstreaming may improve access to cancer genetic testing regionally. Interim results from this study will demonstrate the challenges and the feasibility of introducing mainstreaming cancer genetics in Malaysia.

Legal entity responsible for the study

Cancer Research Malaysia

Funding

Cancer Research Malaysia and Astra Zeneca

Disclosure

S.Y. Yoon: This study is funded by Cancer Research Malaysia and with an Investigator Initiated Grant from Astra Zeneca. Ms Yoon has received honorarium as invited speaker by Astra Zeneca. N. Rahman: Non-executive director of Astra-Zeneca. M.K. Thong, S.H. Teo: Honorarium as speaker from Astra Zeneca. Y.L. Woo: Honorarium as a speaker by Astra Zeneca. All other authors have declared no conflicts of interest.

Background

The standard treatment for locally advanced cervical cancer is CTRT. We tested in a RCT whether outcomes could be improved by NACT-surgery.

Methods

Patients with clinical stages IB2, IIA or IIB squamous cervical cancer were randomized (stratified on stage) to either NACT-surgery arm comprising 3 cycles of paclitaxel (175 mg/m2) and carboplatin (AUC 5-6) every 3 weeks followed by radical hysterectomy or CTRT arm comprising standard pelvic radiation with 5 cycles of cisplatin (40 mg/m2) once per week. Post-operative radiation was given as per protocol criteria. Primary end point was disease-free survival (DFS, relapse or cancer-related death whichever earlier) while secondary end points were overall survival (OS) and toxicity. The trial was designed to demonstrate 10% absolute increase in 5-year DFS in NACT-surgery arm, assuming 65% DFS in CTRT (control) arm (2-sided α = 0.05, power=80%) with planned sample size of 730.

Results

Between September 2003 and February 2015, 635 patients were randomised of whom 633 (316 in neoadjuvant chemotherapy-surgery group and 317 in concurrent chemotherapy-radiotherapy group) are included in final analysis with a median follow-up of 58·5 months. The 5-year disease-free survival in neoadjuvant chemotherapy-surgery group was 69·3% compared with 76·7% (95% CI, 71·6 to 81·8) in concurrent chemotherapy-radiotherapy group while the corresponding 5-year overall survival rates were 75·4% and 74·7%, respectively (hazard ratio 1·025, 95% CI, 0·752 to 1·398, p = 0·87). Early and delayed toxicities were acceptable in both groups with some difference in pattern.

Conclusions

Radiotherapy with concurrent cisplatin-based chemotherapy resulted in superior disease-free survival compared to neoadjuvant chemotherapy followed by radical surgery and should continue to be the standard of care in locally advanced cervical cancer.

Clinical trial identification

NCT00193739

Legal entity responsible for the study

Tata Memorial Centre

Funding

Tata Memorial Centre - Government of India

Disclosure

All authors have declared no conflicts of interest.

Background

HF10 is a bioselected replication-competent oncolytic virus derived from HSV-1. Herein, we report the safety and efficacy data of HF10+ipilimumab (ipi) combination treatment in a Phase II trial in melanoma.

Methods

Ipi naïve patients (pts) with Stage IIIB-IV unresectable melanoma received HF10 injections (inj) into single or multiple dermal, subcutaneous or lymph node tumors (1x10⁷ TCID₅₀/mL, up to 5mL/dose); 4 inj qwk; then up to 15 inj q3wk. Ipi was administered IV (3 mg/kg), q3wk for 4 doses. Tumor responses assessed per irRC at 12, 18, 24, 36 and 48wks. Primary endpoint was Best Overall Response Rate (BORR) at 24wks.

Results

Of 46 pts enrolled and treated: 59% men, median age 67 yrs (range 28 to 91); disease stage 20% IIIB, 43% IIIC & 37% IV; therapy (tx) naïve: 57% and ≥ 1 prior cancer tx: 43% (2 pts received prior immune checkpoint inhibitors). Most HF10-related AEs were ≤G2, similar to HF10 monotherapy. 37% had ≥G3 AEs, the majority due to ipi. HF10-related ≥G3 AEs (n = 3) were embolism, lymphedema, diarrhea, hypoglycemia, and groin pain. Of 44 efficacy evaluable pts per irRC, BORR at 24wks was 41% (18% irCR, 23% irPR); disease control rate was 68% (27% irSD). BORR at 48wks was 45% (18% irCR, 27% irPR). BORR at 24wks in tx naïve pts was 50% (17% irCR, 33% irPR) and pts with ≥1 prior therapies was 30% (20% irCR, 10% irPR). BORR in pts with stages IIIB/IIIC/IVM1a (n = 34) and IVM1b/IVM1c (n = 10) were 47% (21% irCR, 26% irPR) and 20% (10% irCR, 10% irPR), respectively. Median PFS was 19mos and 1-year overall survival rate was 85%. Median PFS in tx naïve and pts with ≥1 prior therapies were 19mos and 22mos, respectively; 1-year overall survival rates in tx naïve and pts with ≥1 prior therapies 87% and 82%, respectively. HF10+ipi treatment resulted in a decrease in lesion size by ≥ 50% in 57% of injected lesions (N = 148), 39% of never injected non-visceral lesions (N = 41) and 14% of never injected visceral lesions (N = 22). Complete resolution of lesions occurred in 30% of injected lesions and 20% of never injected non-visceral lesions.

Conclusions

The combination HF10 and ipi treatment demonstrated a favorable benefit/risk profile and encouraging antitumor activity in unresectable or metastatic melanoma pts.

Clinical trial identification

NCT02272855.

Legal entity responsible for the study

TAKARA BIO INC

Funding

TAKARA BIO INC

Disclosure

R.H.I. Andtbacka: Receipt of grants/research supports: from Takara, Amgen, Viralytics Receipt of honoraria: from Merck, Novartis, M. Ross: Receipt of honoraria or consultation fees: AMGEN, MERCK, PROVECTUS Participation in a company sponsored speaker’s bureau: AMGEN, M. Taylor: Receipt of honoraria or consultation fees: Bristol Myers Squibb, Eisai Inc, Trillium Pharma, Blue Print Medicines. Participation in a company sponsored speaker’s bureau: Bristol Myers Squibb, Eisai Inc. J. Vetto: Receipt of grants/research supports: none Receipt of honoraria or consultation fees: Castle Biosciences, Novartis Participation in a company sponsored speaker’s bureau: Castle Biosciences, Amgen Stock shareholder (Yes/No): No Spouse/Partner (Yes/No): Yes; salary and stock (Roche)

All other authors have declared no conflicts of interest.