- Email: [email protected]
2803 Carbon ion radiotherapy for locally advanced parotid gland carcinomas
S558
Abstracts
2801 ORAL Antitumor activity and safety of pembrolizumab in patients with PD-L1-positive nasopharyngeal carcinoma: Interim results from a phase 1b study
2802 ORAL Phase II study of first-line paclitaxel (PTX) with panitumumab (P) in patients with metastatic or recurrent head and neck cancer: TTCC-2009−03 study
C. Hsu1 , S.H. Lee2 , S. Ejadi3 , C. Even4 , R. Cohen5 , C. Le Tourneau6 , J. Mehnert7 , A. Algazi8 , E. Van Brummelen9 , S.S. Yuan10 , P. Thanigaimani11 , J. Cheng12 , A. Hansen13 . 1 National Taiwan University Hospital, Oncology, Taipei, Taiwan; 2 Seoul National University Hospital, Internal Medicine, Seoul, Korea; 3 Virginia G. Piper Cancer Center, Clinical Trials, Scottsdale, USA; 4 Gustave Roussy, Head and Neck, Villejuif, France; 5 Perelman School of Medicine at the University of Pennsylvania, Hematology and Oncology, Philadelphia, USA; 6 Institut Curie, Medical Oncology, Paris, France; 7 Rutgers Cancer Institute of New Jersey, Medical Oncology, New Brunswick, USA; 8 University of California San Francisco, Medicine: Hematology/Oncology, San Francisco, USA; 9 Netherlands Cancer Institute, Clinical Pharmacology, Amsterdam, Netherlands; 10 Merck & Co. Inc., BARDS, Kenilworth, USA; 11 Merck & Co. Inc., Clinical Development Execution Organization, Kenilworth, USA; 12 Merck & Co. Inc., Clinical Oncology, Kenilworth, USA; 13 Princess Margaret Cancer Centre, Medical Oncology and Hematology, Toronto, Canada
E. Del Barco Morillo1 , R. Mesia2 , J.C. Adansa Klain1 , S. Vazquez 2 Fernandez ´ , J. Mart´ınez Galan3 , M. Pastor Borgonon ˜ 4 , C. Gonzalez ´ Rivas3 , J. Caballero Daroqui4 , A. Berrocal5 , J. Mart´ınez Trufero6 , J.J. Cruz 1 Hernandez ´ , R. Vera7 . 1 H. Universitario de Salamanca, Oncology Unit, Salamanca, Spain; 2 ICO H. Duran y Reynals, Oncology Unit, L’Hospitalet de Llobregat, Spain; 3 H. Virgen de las Nieves, Oncology Unit, Granada, Spain; 4 H. La Fe de Valencia, Oncology Unit, Valencia, Spain; 5 H. General de Valencia, Oncology Unit, Valencia, Spain; 6 H. Miguel Servet, Oncology Unit, Zaragoza, Spain; 7 H. de Navarra, Oncology Unit, Pamplona, Spain
Background: Engagement of the programmed death 1 (PD-1) receptor by its ligands, PD-L1 and PD-L2, normally down-regulates T-cell effector activity. Many tumors express PD-L1 and may employ this pathway to evade antitumor immunity. Nasopharyngeal carcinoma (NPC) exhibits high expression of PD-1, and expression of PD-1/PD-L1 in these tumors correlated with poor outcome. Pembrolizumab is a potent, highly selective humanized monoclonal antibody against PD-1 designed to block interaction with PD-L1 and PD-L2 and thereby enhance antitumor immune response. We present results on the safety and antitumor activity of pembrolizumab in patients (pts) with PD-L1-positive (PD-L1+ ) advanced NPC. Methods: KEYNOTE-028 (NCT02054806) is a nonrandomized, multicohort phase 1b trial of pembrolizumab in pts with PD-L1+ advanced solid tumors. Key eligibility criteria for the NPC cohort included advanced (unresectable and/or metastatic) solid tumor, a failure of prior therapy, PD-L1 expression in 1% of cells in tumor nests or PD-L1+ bands in stroma as determined by a prototype immunohistochemical assay at a central laboratory, and ECOG performance status 0−1. Pembrolizumab 10 mg/kg was given every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points were safety, tolerability, and preliminary efficacy. Response was assessed per RECIST v1.1 by investigators every 8 weeks for the first 6 months and every 12 weeks thereafter. Results: 27 pts were enrolled. Median (range) age was 52.0 (18−68) years; 63% were Asian. 92.5% received prior therapies for recurrent/ metastatic disease (33.3% received 5 therapies). One pt experienced a complete response, 6 pts experienced partial responses and 14 had stable disease. The best overall (confirmed and unconfirmed) response rate was 25.9% (95% CI, 11.1–46.3). Most common adverse events (AEs) (20%) were fatigue (33.3%), pruritus (29.6%), nausea (25.9%), and pyrexia (25.9%). Drug-related AEs occurred in 70.4% of pts; most common (10%) were pruritus (25.9%), fatigue (11.1%), rash (11.1%), maculo-papular rash (11.1%), pneumonitis (11.1%), herpes zoster infection (11.1%), and hypothyroidism (11.1%); grade 3 AEs occurred in 6/27 (22.2%) pts. Currently 8 pts remain on pembrolizumab treatment. Conclusion: This is the first demonstration of clinical activity of PD-1 blockade in patients with recurrent/metastatic NPC. Pembrolizumab was well tolerated and had significant antitumor activity as assessed by confirmed and unconfirmed response rate (25.9%) in pts with NPC. This preliminary signal for clinical efficacy will be further investigated. Conflict of interest: Advisory Board: JM has served on advisory boards for Amgen. Corporate-sponsored Research: JM has received research funding from Amgen, Novartis, Merck, and Sanofi-Aventis. AA has received research funding from Merck. Other Substantive Relationships: SSY is an employee of and holds stock in Merck & Co. PT is an employee of Merck & Co. and holds stock in Gilead Sciences. JC is an employee of and holds stock in Merck Sharpe and Dohme.
Background: Cisplatin based combinations have become a standard firstline treatment for patients (pts) with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). Pts not candidates to platinum based therapies have limited treatment options and a poor prognosis. Single agent treatment with PTX in locoregionally recurrent or metastatic SCCHN has been associated with response rates comparable with that of cisplatin plus 5-FU chemotherapy. The addition of P to PTX may have an additive anti-tumour effect and may be an alternative to the platinum-based therapy. This study aimed to evaluate the activity of P plus PTX in pts with metastatic or recurrent SCCHN. Methods: This was a phase II, open-label, multicenter study, started in March 2011, which included pts18 years with histologically or cytologically confirmed SCCHN, diagnosis of metastatic and/or recurrent disease determined to be incurable by surgery or radiotherapy, with prior radiotherapy (if any) completed >4 weeks before and prior chemotherapy completed >24 weeks before. All pts received PTX (80 mg/m2 /week) + P (6 mg/kg every 2 weeks) until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate. We present preliminary results. Results: The study included 40 pts: median 60.8 years (range 43−83), 87.5% men, 72.5% had undergone surgery, 85% had received prior radiotherapy and 57.5% prior CT (35.0% 2 lines; 77.3% of CT-lines platinum-based). Confirmed response was noted in 47.5% of pts (95% confidence interval [CI]: 32.0–63.0), 15.0% complete and 32.5% partial responses. Stable disease was obtained in 27.5% of pts (disease control rate: 75.0% (95% CI: 61.6–88.4). Non-confirmed response was 67.5% (15.0% complete, 52.5% partial). Median progression-free survival was 7.5 months (95% CI: 4.9−8.3) and median overall survival was 9.9 months (95% CI: 7.9–16.3). Incidence of grade 3/4 P- and PTX-related Adverse Events (AEs) were 65.0% and 62.5%, respectively, and in 25.0% and 32.5% of pts there were P- and/or PTX-related AEs that led to treatment discontinuation. Most frequent grade 3/4 P-related AEs (>5% of pts) were: 47.5% skin toxicity, 7.5% hypomagnesaemia, 7.5% asthenia, 7.5% dry skin. Most frequent grade 3/4 PTX-related AEs were: 17.5% asthenia, 15.0% neurotoxicity, 12.5% skin toxicity, 10.0% neutropenia, 7.5% infections and 7.5% mucosal inflammation. There were 6 (15.0%) fatal AEs (febrile neutropenia, gastrointestinal haemorrhage, pulmonary embolism (2), respiratory insufficiency, cervical haemorrhage), from which 1 (febrile neutropenia) was related to both P and PTX. Conclusions: In pts with metastatic or recurrent SCCHN refractory to prior surgery, RT or CT, PTX combined with P had clinically significant benefit with an acceptable safety profile. Study supported by Amgen S.A. ClinicalTrials.gov identifier: NCT01264328. No conflict of interest. 2803 ORAL Carbon ion radiotherapy for locally advanced parotid gland carcinomas M. Koto1 , R. Takagi1 , H. Ikawa1 , K. Naganawa1 , T. Kamada1 . 1 National Institute of Radiological Sciences, Research Center for Charged Particle Therapy Hospital, Chiba, Japan Background: Parotid gland carcinomas include many different histological types; however, most of them are not radio-sensitive. Therefore, the prognoses of patients with inoperable parotid gland carcinomas are poor. Carbon ions have a higher relative biological effectiveness (RBE), increasing the probability of tumor control compared with photons. Additionally, the physical characteristics of carbon ions offer a theoretical benefit of a more localized delivery of a radiation dose than with photons. The improved dose distribution can potentially be exploited either by allowing higher radiation doses to the tumor with less radiation-induced normal tissue toxicity or by reducing adverse effects at equivalent effective doses. The purpose of this study was to evaluate the safety and efficacy
Abstracts of carbon ion radiotherapy (C-ion RT) for locally advanced parotid gland carcinomas. Material and Methods: Forty-six patients with parotid gland carcinomas were treated with C-ion RT between May 1997 and April 2012. Twenty-one patients were men and 25 were women. The median age was 57 years (range, 16−80 years). T-classification of the carcinomas, according to the Union of International Cancer Control stages, was diagnosed as T2 in 3 patients, T3 in 18, T4a in 8, and T4b in 17. N-classification was diagnosed as N0 in 34 patients, N1 in 6, and N2b in 6. In particular, 16 patients had adenoid cystic carcinoma, 8 adenocarcinoma, 8 mucoepidermoid carcinoma, and 6 acinic cell carcinoma. Twenty-five patients received C-ion RT as the primary treatment. Twenty patients had local recurrences and 1 had a residual tumor after surgery. Thirty patients had no facial nerve palsy before C-ion RT. Twenty-six patients were treated with a total dose of 57.6 Gy (RBE) in 16 fractions, and 20 with a total dose of 64.0 Gy (RBE) in 16 fractions. Acute and late reactions of normal tissues were classified according to the NCI-CTCAE v4.0. During C-ion RT, patients did not undergo any concomitant therapy. After completion of C-ion RT, patients did not undergo adjuvant therapy such as surgery or chemotherapy. When local recurrence and/or distant metastasis were diagnosed, the treatment methods for these tumors were not limited. Results: The median follow-up period was 62 months (range, 4– 186 months). The 5-year local control rate was 74.5%. The 5-year overall survival and disease-free survival rates were 70.1% and 49.2%, respectively. With respect to acute reactions, grade 3 skin reaction was observed in 1 patient. Regarding late reactions, one patient developed grade 3 mandible osteoradionecrosis, 1 ipsilateral blindness, and 5 ipsilateral hearing loss. Of the 30 patients without facial nerve palsy, 25 did not show any facial nerve palsy during follow-up periods. Conclusions: C-ion RT is effective and has acceptable toxicity levels for the treatment of locally advanced parotid gland carcinomas. No conflict of interest. 2804 ORAL Primary surgery for advanced oropharyngeal and hypopharyngeal cancers: A nationwide study in Taiwan C.T. Cheng1 , S.D. Terng2 , C.Y. Lin2 , Z.Y. Liu1 , N. Pennarun1 , W.H. Kao3 , J.Y. Wu4 , Y.P. Lin1 . 1 Koo Foundation Sun Yat-Sen Cancer Center, Medical research, Taipei City, Taiwan; 2 Koo Foundation Sun Yat-Sen Cancer Center, ENT, Taipei City, Taiwan; 3 Koo Foundation Sun Yat-Sen Cancer Center, Biostatistics, Taipei City, Taiwan; 4 Koo Foundation Sun Yat-Sen Cancer Center, Health policy research, Taipei City, Taiwan Background: Recommending primary surgery or concurrent chemoradiotherapy (CCRT) for advanced oropharyngeal and hypopharyngeal cancer patients remains controversial. Randomized clinical trials for head-tohead comparison of these two approaches for cancer survival often face difficulties in recruiting enough patients. Therefore, we used a nationwide dataset for larger sample recruitment. We investigated the associated cancer survival in this population between patients who received primary surgery and patients who did not. Furthermore, we conducted a stratified analysis to evaluate the survival benefit difference among patients with different cancer stage, tumor size, and lymph node positivity. Material and Methods: The Taiwan National Health Insurance Claims Database and Taiwan Cancer Registry Database were used in this study. We identified 2,387 oropharyngeal and 2,315 hypopharyngeal newly diagnosed cancer patients between 2004 and 2009. The study cohort was followed up until 2012. Results: Radical surgery was performed on 35.29% and 37.63% of stage 3 and stage 4A oropharyngeal cancer patients, respectively, and 54.52% and 48.85% of stage 3 and stage 4A hypopharyngeal cancer patients, respectively. Primary surgery was associated with better overall cancer survival in most subset analysis. Conclusions: Primary surgery for advanced oropharyngeal and hypopharyngeal cancer is associated with better overall cancer survival in our study population. No conflict of interest.
S559 2805 ORAL Overall survival gain with lenvatinib vs. placebo in radioactive iodine refractory differentiated thyroid cancer (RR-DTC): An updated analysis M. Guo1 , S. Sherman2 , L. Wirth3 , M. Schlumberger4 , C. Dutcus1 , B. Robinson5 , M. Tahara6 , N. Latimer7 . 1 Eisai Inc, Woodcliff Lake, NJ, USA; 2 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston TX, USA; 3 Department of Medicine, Massachusetts General Hospital, Boston MA, USA; 4 Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris-Sud, Villejuif, France; 5 Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia; 6 Department of Head and Neck, National Cancer Center Hospital East, Kashiwa, Japan; 7 ScHARR, University of Sheffield, Sheffield, United Kingdom Background: Lenvatinib has recently received marketing authorization in the USA and Japan; and positive CHMP (Committee for Medicinal Products for Human Use) opinion in Europe for use in Progressive RRDTC. At the original cut-off date for primary efficacy analysis of the phase 3 SELECT trial (15-Nov-2013), evaluation of overall survival (OS), a secondary endpoint, was premature. An updated OS analysis was performed at a later cut-off date to include a longer time horizon (15-Jun2014). Methods: The SELECT was a multicentre, randomised, double-blind, placebo-controlled trial in 392 RR-DTC patients. At the first cut-off date, the median OS was not yet reached for either the lenvatinib or placebo arms. OS analysis was confounded by the fact that 83.2% of placebotreated subjects with confirmed disease progression switched to open-label lenvatinib at the first data cut-off (87.8% − updated data cut-off). To adjust for crossover and to estimate the true OS treatment effect (the effect that would have been observed in the absence of switching), a Rank preserving structural failure time (RPSFT) model was used. OS curves were estimated using Kaplan–Meier method and the hazard ratio (HR) was estimated with a Cox proportional hazard model fitted to RPSFT-adjusted OS data. The 95% confidence interval (CI) and p-value for HR was estimated using a resampling method (bootstrapping). Multiplicity was not adjusted for the second analysis. Results: In the original analysis, there was no statistically significant difference in OS between the treatment groups without adjustment for crossover, (HR = 0.73; 95% CI: 0.50, 1.07, P = 0.1032). With the RPSFT adjustment, HR was 0.62 (95% CI: 0.40, 1.00), indicating a trend for longer survival for the lenvatinib arm vs. the placebo crossover arm (P = 0.0510). In the updated OS analysis, the unadjusted HR for OS was 0.80 (95% CI: 0.57, 1.12; nominal P = 0.1993). The RPSFT-adjusted HR showed a significant difference in OS between the treatment groups (HR = 0.53; 95% CI: 0.34, 0.82, nominal P = 0.0051) as determined using the resampling method (bootstrapping). Median OS had not been reached after 34 months of the trial for the lenvatinib arm, and was 19.1 months (95% CI: 14.3, not estimable [NE]) in the placebo crossover arm. Conclusions: In this updated survival analysis with RPSFT adjustment for crossover, lenvatinib significantly improved OS vs. placebo crossover arm in patients with progressive RR-DTC. 1st Data Cut Number of deaths (%) Median OS months (95% CI) Unadjusted HR (95% CI) RPSFT-adjusted HR (95% CI) 2nd Data Cut Number of deaths (%) Median OS months (95% CI) Unadjusted HR (95% CI) RPSFT-adjusted HR (95% CI)
71 (27.2) 47 (35.9) NE (22.0, NE) NE (20.3, NE) 0.73 (0.50, 1.07), P = 0.1032 0.62 (0.40, 1.00), P = 0.0510 93 (35.6) 55 (42.0) NE (30.9, NE) 19.1 (14.3, NE) 0.80 (0.57, 1.12), nominal P = 0.1993 0.53 (0.34, 0.82), nominal P = 0.0051
Conflict of interest: Ownership: None. Advisory Board: SS: Eisai, Bayer, Exelixis, Amgen, Pfizer, AstraZeneca, Roche. LW: Eisai, Novartis. MS: Eisai, AstraZeneca, Bayer, Genzyme-Sanofi, Sobi. BR: Eisai, AstraZeneca, Bayer. MT: Eisai, Merck Serono, BMS, Bayer. Board of Directors: None. Corporate-sponsored Research: SS: Amgen. MS: AstraZeneca, Bayer, Eisai, Genzyme-Sanofi. MT: Eisai, Boehringer-Ingelheim. NL: Eisai. Other Substantive Relationships: MG & CD: Eisai Employees. SS: Exelixis.
Abstracts
2801 ORAL Antitumor activity and safety of pembrolizumab in patients with PD-L1-positive nasopharyngeal carcinoma: Interim results from a phase 1b study
2802 ORAL Phase II study of first-line paclitaxel (PTX) with panitumumab (P) in patients with metastatic or recurrent head and neck cancer: TTCC-2009−03 study
C. Hsu1 , S.H. Lee2 , S. Ejadi3 , C. Even4 , R. Cohen5 , C. Le Tourneau6 , J. Mehnert7 , A. Algazi8 , E. Van Brummelen9 , S.S. Yuan10 , P. Thanigaimani11 , J. Cheng12 , A. Hansen13 . 1 National Taiwan University Hospital, Oncology, Taipei, Taiwan; 2 Seoul National University Hospital, Internal Medicine, Seoul, Korea; 3 Virginia G. Piper Cancer Center, Clinical Trials, Scottsdale, USA; 4 Gustave Roussy, Head and Neck, Villejuif, France; 5 Perelman School of Medicine at the University of Pennsylvania, Hematology and Oncology, Philadelphia, USA; 6 Institut Curie, Medical Oncology, Paris, France; 7 Rutgers Cancer Institute of New Jersey, Medical Oncology, New Brunswick, USA; 8 University of California San Francisco, Medicine: Hematology/Oncology, San Francisco, USA; 9 Netherlands Cancer Institute, Clinical Pharmacology, Amsterdam, Netherlands; 10 Merck & Co. Inc., BARDS, Kenilworth, USA; 11 Merck & Co. Inc., Clinical Development Execution Organization, Kenilworth, USA; 12 Merck & Co. Inc., Clinical Oncology, Kenilworth, USA; 13 Princess Margaret Cancer Centre, Medical Oncology and Hematology, Toronto, Canada
E. Del Barco Morillo1 , R. Mesia2 , J.C. Adansa Klain1 , S. Vazquez 2 Fernandez ´ , J. Mart´ınez Galan3 , M. Pastor Borgonon ˜ 4 , C. Gonzalez ´ Rivas3 , J. Caballero Daroqui4 , A. Berrocal5 , J. Mart´ınez Trufero6 , J.J. Cruz 1 Hernandez ´ , R. Vera7 . 1 H. Universitario de Salamanca, Oncology Unit, Salamanca, Spain; 2 ICO H. Duran y Reynals, Oncology Unit, L’Hospitalet de Llobregat, Spain; 3 H. Virgen de las Nieves, Oncology Unit, Granada, Spain; 4 H. La Fe de Valencia, Oncology Unit, Valencia, Spain; 5 H. General de Valencia, Oncology Unit, Valencia, Spain; 6 H. Miguel Servet, Oncology Unit, Zaragoza, Spain; 7 H. de Navarra, Oncology Unit, Pamplona, Spain
Background: Engagement of the programmed death 1 (PD-1) receptor by its ligands, PD-L1 and PD-L2, normally down-regulates T-cell effector activity. Many tumors express PD-L1 and may employ this pathway to evade antitumor immunity. Nasopharyngeal carcinoma (NPC) exhibits high expression of PD-1, and expression of PD-1/PD-L1 in these tumors correlated with poor outcome. Pembrolizumab is a potent, highly selective humanized monoclonal antibody against PD-1 designed to block interaction with PD-L1 and PD-L2 and thereby enhance antitumor immune response. We present results on the safety and antitumor activity of pembrolizumab in patients (pts) with PD-L1-positive (PD-L1+ ) advanced NPC. Methods: KEYNOTE-028 (NCT02054806) is a nonrandomized, multicohort phase 1b trial of pembrolizumab in pts with PD-L1+ advanced solid tumors. Key eligibility criteria for the NPC cohort included advanced (unresectable and/or metastatic) solid tumor, a failure of prior therapy, PD-L1 expression in 1% of cells in tumor nests or PD-L1+ bands in stroma as determined by a prototype immunohistochemical assay at a central laboratory, and ECOG performance status 0−1. Pembrolizumab 10 mg/kg was given every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points were safety, tolerability, and preliminary efficacy. Response was assessed per RECIST v1.1 by investigators every 8 weeks for the first 6 months and every 12 weeks thereafter. Results: 27 pts were enrolled. Median (range) age was 52.0 (18−68) years; 63% were Asian. 92.5% received prior therapies for recurrent/ metastatic disease (33.3% received 5 therapies). One pt experienced a complete response, 6 pts experienced partial responses and 14 had stable disease. The best overall (confirmed and unconfirmed) response rate was 25.9% (95% CI, 11.1–46.3). Most common adverse events (AEs) (20%) were fatigue (33.3%), pruritus (29.6%), nausea (25.9%), and pyrexia (25.9%). Drug-related AEs occurred in 70.4% of pts; most common (10%) were pruritus (25.9%), fatigue (11.1%), rash (11.1%), maculo-papular rash (11.1%), pneumonitis (11.1%), herpes zoster infection (11.1%), and hypothyroidism (11.1%); grade 3 AEs occurred in 6/27 (22.2%) pts. Currently 8 pts remain on pembrolizumab treatment. Conclusion: This is the first demonstration of clinical activity of PD-1 blockade in patients with recurrent/metastatic NPC. Pembrolizumab was well tolerated and had significant antitumor activity as assessed by confirmed and unconfirmed response rate (25.9%) in pts with NPC. This preliminary signal for clinical efficacy will be further investigated. Conflict of interest: Advisory Board: JM has served on advisory boards for Amgen. Corporate-sponsored Research: JM has received research funding from Amgen, Novartis, Merck, and Sanofi-Aventis. AA has received research funding from Merck. Other Substantive Relationships: SSY is an employee of and holds stock in Merck & Co. PT is an employee of Merck & Co. and holds stock in Gilead Sciences. JC is an employee of and holds stock in Merck Sharpe and Dohme.
Background: Cisplatin based combinations have become a standard firstline treatment for patients (pts) with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). Pts not candidates to platinum based therapies have limited treatment options and a poor prognosis. Single agent treatment with PTX in locoregionally recurrent or metastatic SCCHN has been associated with response rates comparable with that of cisplatin plus 5-FU chemotherapy. The addition of P to PTX may have an additive anti-tumour effect and may be an alternative to the platinum-based therapy. This study aimed to evaluate the activity of P plus PTX in pts with metastatic or recurrent SCCHN. Methods: This was a phase II, open-label, multicenter study, started in March 2011, which included pts18 years with histologically or cytologically confirmed SCCHN, diagnosis of metastatic and/or recurrent disease determined to be incurable by surgery or radiotherapy, with prior radiotherapy (if any) completed >4 weeks before and prior chemotherapy completed >24 weeks before. All pts received PTX (80 mg/m2 /week) + P (6 mg/kg every 2 weeks) until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate. We present preliminary results. Results: The study included 40 pts: median 60.8 years (range 43−83), 87.5% men, 72.5% had undergone surgery, 85% had received prior radiotherapy and 57.5% prior CT (35.0% 2 lines; 77.3% of CT-lines platinum-based). Confirmed response was noted in 47.5% of pts (95% confidence interval [CI]: 32.0–63.0), 15.0% complete and 32.5% partial responses. Stable disease was obtained in 27.5% of pts (disease control rate: 75.0% (95% CI: 61.6–88.4). Non-confirmed response was 67.5% (15.0% complete, 52.5% partial). Median progression-free survival was 7.5 months (95% CI: 4.9−8.3) and median overall survival was 9.9 months (95% CI: 7.9–16.3). Incidence of grade 3/4 P- and PTX-related Adverse Events (AEs) were 65.0% and 62.5%, respectively, and in 25.0% and 32.5% of pts there were P- and/or PTX-related AEs that led to treatment discontinuation. Most frequent grade 3/4 P-related AEs (>5% of pts) were: 47.5% skin toxicity, 7.5% hypomagnesaemia, 7.5% asthenia, 7.5% dry skin. Most frequent grade 3/4 PTX-related AEs were: 17.5% asthenia, 15.0% neurotoxicity, 12.5% skin toxicity, 10.0% neutropenia, 7.5% infections and 7.5% mucosal inflammation. There were 6 (15.0%) fatal AEs (febrile neutropenia, gastrointestinal haemorrhage, pulmonary embolism (2), respiratory insufficiency, cervical haemorrhage), from which 1 (febrile neutropenia) was related to both P and PTX. Conclusions: In pts with metastatic or recurrent SCCHN refractory to prior surgery, RT or CT, PTX combined with P had clinically significant benefit with an acceptable safety profile. Study supported by Amgen S.A. ClinicalTrials.gov identifier: NCT01264328. No conflict of interest. 2803 ORAL Carbon ion radiotherapy for locally advanced parotid gland carcinomas M. Koto1 , R. Takagi1 , H. Ikawa1 , K. Naganawa1 , T. Kamada1 . 1 National Institute of Radiological Sciences, Research Center for Charged Particle Therapy Hospital, Chiba, Japan Background: Parotid gland carcinomas include many different histological types; however, most of them are not radio-sensitive. Therefore, the prognoses of patients with inoperable parotid gland carcinomas are poor. Carbon ions have a higher relative biological effectiveness (RBE), increasing the probability of tumor control compared with photons. Additionally, the physical characteristics of carbon ions offer a theoretical benefit of a more localized delivery of a radiation dose than with photons. The improved dose distribution can potentially be exploited either by allowing higher radiation doses to the tumor with less radiation-induced normal tissue toxicity or by reducing adverse effects at equivalent effective doses. The purpose of this study was to evaluate the safety and efficacy
Abstracts of carbon ion radiotherapy (C-ion RT) for locally advanced parotid gland carcinomas. Material and Methods: Forty-six patients with parotid gland carcinomas were treated with C-ion RT between May 1997 and April 2012. Twenty-one patients were men and 25 were women. The median age was 57 years (range, 16−80 years). T-classification of the carcinomas, according to the Union of International Cancer Control stages, was diagnosed as T2 in 3 patients, T3 in 18, T4a in 8, and T4b in 17. N-classification was diagnosed as N0 in 34 patients, N1 in 6, and N2b in 6. In particular, 16 patients had adenoid cystic carcinoma, 8 adenocarcinoma, 8 mucoepidermoid carcinoma, and 6 acinic cell carcinoma. Twenty-five patients received C-ion RT as the primary treatment. Twenty patients had local recurrences and 1 had a residual tumor after surgery. Thirty patients had no facial nerve palsy before C-ion RT. Twenty-six patients were treated with a total dose of 57.6 Gy (RBE) in 16 fractions, and 20 with a total dose of 64.0 Gy (RBE) in 16 fractions. Acute and late reactions of normal tissues were classified according to the NCI-CTCAE v4.0. During C-ion RT, patients did not undergo any concomitant therapy. After completion of C-ion RT, patients did not undergo adjuvant therapy such as surgery or chemotherapy. When local recurrence and/or distant metastasis were diagnosed, the treatment methods for these tumors were not limited. Results: The median follow-up period was 62 months (range, 4– 186 months). The 5-year local control rate was 74.5%. The 5-year overall survival and disease-free survival rates were 70.1% and 49.2%, respectively. With respect to acute reactions, grade 3 skin reaction was observed in 1 patient. Regarding late reactions, one patient developed grade 3 mandible osteoradionecrosis, 1 ipsilateral blindness, and 5 ipsilateral hearing loss. Of the 30 patients without facial nerve palsy, 25 did not show any facial nerve palsy during follow-up periods. Conclusions: C-ion RT is effective and has acceptable toxicity levels for the treatment of locally advanced parotid gland carcinomas. No conflict of interest. 2804 ORAL Primary surgery for advanced oropharyngeal and hypopharyngeal cancers: A nationwide study in Taiwan C.T. Cheng1 , S.D. Terng2 , C.Y. Lin2 , Z.Y. Liu1 , N. Pennarun1 , W.H. Kao3 , J.Y. Wu4 , Y.P. Lin1 . 1 Koo Foundation Sun Yat-Sen Cancer Center, Medical research, Taipei City, Taiwan; 2 Koo Foundation Sun Yat-Sen Cancer Center, ENT, Taipei City, Taiwan; 3 Koo Foundation Sun Yat-Sen Cancer Center, Biostatistics, Taipei City, Taiwan; 4 Koo Foundation Sun Yat-Sen Cancer Center, Health policy research, Taipei City, Taiwan Background: Recommending primary surgery or concurrent chemoradiotherapy (CCRT) for advanced oropharyngeal and hypopharyngeal cancer patients remains controversial. Randomized clinical trials for head-tohead comparison of these two approaches for cancer survival often face difficulties in recruiting enough patients. Therefore, we used a nationwide dataset for larger sample recruitment. We investigated the associated cancer survival in this population between patients who received primary surgery and patients who did not. Furthermore, we conducted a stratified analysis to evaluate the survival benefit difference among patients with different cancer stage, tumor size, and lymph node positivity. Material and Methods: The Taiwan National Health Insurance Claims Database and Taiwan Cancer Registry Database were used in this study. We identified 2,387 oropharyngeal and 2,315 hypopharyngeal newly diagnosed cancer patients between 2004 and 2009. The study cohort was followed up until 2012. Results: Radical surgery was performed on 35.29% and 37.63% of stage 3 and stage 4A oropharyngeal cancer patients, respectively, and 54.52% and 48.85% of stage 3 and stage 4A hypopharyngeal cancer patients, respectively. Primary surgery was associated with better overall cancer survival in most subset analysis. Conclusions: Primary surgery for advanced oropharyngeal and hypopharyngeal cancer is associated with better overall cancer survival in our study population. No conflict of interest.
S559 2805 ORAL Overall survival gain with lenvatinib vs. placebo in radioactive iodine refractory differentiated thyroid cancer (RR-DTC): An updated analysis M. Guo1 , S. Sherman2 , L. Wirth3 , M. Schlumberger4 , C. Dutcus1 , B. Robinson5 , M. Tahara6 , N. Latimer7 . 1 Eisai Inc, Woodcliff Lake, NJ, USA; 2 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston TX, USA; 3 Department of Medicine, Massachusetts General Hospital, Boston MA, USA; 4 Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University Paris-Sud, Villejuif, France; 5 Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia; 6 Department of Head and Neck, National Cancer Center Hospital East, Kashiwa, Japan; 7 ScHARR, University of Sheffield, Sheffield, United Kingdom Background: Lenvatinib has recently received marketing authorization in the USA and Japan; and positive CHMP (Committee for Medicinal Products for Human Use) opinion in Europe for use in Progressive RRDTC. At the original cut-off date for primary efficacy analysis of the phase 3 SELECT trial (15-Nov-2013), evaluation of overall survival (OS), a secondary endpoint, was premature. An updated OS analysis was performed at a later cut-off date to include a longer time horizon (15-Jun2014). Methods: The SELECT was a multicentre, randomised, double-blind, placebo-controlled trial in 392 RR-DTC patients. At the first cut-off date, the median OS was not yet reached for either the lenvatinib or placebo arms. OS analysis was confounded by the fact that 83.2% of placebotreated subjects with confirmed disease progression switched to open-label lenvatinib at the first data cut-off (87.8% − updated data cut-off). To adjust for crossover and to estimate the true OS treatment effect (the effect that would have been observed in the absence of switching), a Rank preserving structural failure time (RPSFT) model was used. OS curves were estimated using Kaplan–Meier method and the hazard ratio (HR) was estimated with a Cox proportional hazard model fitted to RPSFT-adjusted OS data. The 95% confidence interval (CI) and p-value for HR was estimated using a resampling method (bootstrapping). Multiplicity was not adjusted for the second analysis. Results: In the original analysis, there was no statistically significant difference in OS between the treatment groups without adjustment for crossover, (HR = 0.73; 95% CI: 0.50, 1.07, P = 0.1032). With the RPSFT adjustment, HR was 0.62 (95% CI: 0.40, 1.00), indicating a trend for longer survival for the lenvatinib arm vs. the placebo crossover arm (P = 0.0510). In the updated OS analysis, the unadjusted HR for OS was 0.80 (95% CI: 0.57, 1.12; nominal P = 0.1993). The RPSFT-adjusted HR showed a significant difference in OS between the treatment groups (HR = 0.53; 95% CI: 0.34, 0.82, nominal P = 0.0051) as determined using the resampling method (bootstrapping). Median OS had not been reached after 34 months of the trial for the lenvatinib arm, and was 19.1 months (95% CI: 14.3, not estimable [NE]) in the placebo crossover arm. Conclusions: In this updated survival analysis with RPSFT adjustment for crossover, lenvatinib significantly improved OS vs. placebo crossover arm in patients with progressive RR-DTC. 1st Data Cut Number of deaths (%) Median OS months (95% CI) Unadjusted HR (95% CI) RPSFT-adjusted HR (95% CI) 2nd Data Cut Number of deaths (%) Median OS months (95% CI) Unadjusted HR (95% CI) RPSFT-adjusted HR (95% CI)
71 (27.2) 47 (35.9) NE (22.0, NE) NE (20.3, NE) 0.73 (0.50, 1.07), P = 0.1032 0.62 (0.40, 1.00), P = 0.0510 93 (35.6) 55 (42.0) NE (30.9, NE) 19.1 (14.3, NE) 0.80 (0.57, 1.12), nominal P = 0.1993 0.53 (0.34, 0.82), nominal P = 0.0051
Conflict of interest: Ownership: None. Advisory Board: SS: Eisai, Bayer, Exelixis, Amgen, Pfizer, AstraZeneca, Roche. LW: Eisai, Novartis. MS: Eisai, AstraZeneca, Bayer, Genzyme-Sanofi, Sobi. BR: Eisai, AstraZeneca, Bayer. MT: Eisai, Merck Serono, BMS, Bayer. Board of Directors: None. Corporate-sponsored Research: SS: Amgen. MS: AstraZeneca, Bayer, Eisai, Genzyme-Sanofi. MT: Eisai, Boehringer-Ingelheim. NL: Eisai. Other Substantive Relationships: MG & CD: Eisai Employees. SS: Exelixis.