bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor immune microenvironment (TiME) changes by multiplex IF staining in a pilot study of neoadjuvant talazoparib for early-stage breast cancer patients with a BRCA mutation.
Authors: Hobbs Evthokia , Yang Fei , Kumar Tapsi , Contreras Alejandro , Parra Cuentas Edwin Roger , Garber Haven , Scoggins Marion , Adrada Beatriz E , Whitman Gary J , Arun Banu , Mittendorf Elizabeth A. , Litton Jennifer Keating 
Published: May 2019

585 Background: We previously reported a median tumor volume loss of 88% (range 30-98%) in 13 patients with early stage BRCA1/2 mutant breast cancer treated on a neoadjuvant trial of the PARP inhibitor talazoparib. The effects of PARP inhibition on immune aspects of the TiME in early-stage breast cancer has not been well described. The goal of this study was to evaluate the TiME in pre and post-treatment core biopsies from enrolled patients. Methods: Eleven paired core biopsies were available for examination. Tumor infiltrating lymphocytes (TILs) were quantified by H&E stained slides by a central pathologist. Specimens were assessed by multiplex immunofluorescence (mIF) using a panel of 6 biomarkers (PD-1, PD-L1, CD3, CD8, CD68 and CK) with the Opal 7-color Kit in LEICA BOND auto stainer, Vectra automated quantitative pathology imaging system and inForm software (PerkinElmer). Results: In the analyzed core biopsies, there was an increase in TILs evaluated by H&E in post-treatment compared to baseline (mean 36 vs 11%). By mIF there was an increase in CD3+ T cell and CD3+CD8+ cytotoxic T cell density in post-treatment samples compared to baseline, summarized in table. PD-L1 expression in tumor cells was rare in the cohort. There was no difference in CD3+PD-1+ or CD3+CD8+ PD-1+ lymphocytes in pre and post-treatment specimens. There was also no differences in macrophages (CD68+). Evaluation of immune phenotype and imaging response will be presented in the final analysis. Conclusions: This is the first study phenotyping the immune response to neoadjuvant talazoparib in BRCA-mutant breast cancer patients. In this small cohort, intratumoral and stromal CD3+ T cells and CD3+CD8+ cytotoxic T cells increased after two months of talazoparib. Clinical trial information: NCT02282345. [Table: see text]
Evidence that neoadjuvant anthracycline based combination chemotherapy (NACT) in breast cancer (BC) induces phenotypical changes which guides the optimal adjuvant therapy.
Authors: Abdel-Fatah Tarek Mohamed Ahmed , Webb Rebekah , Li Ruizhe , Chen Xin , Giannotti Elisabetta , Auer Dorothee , Walker Jennifer , Moseley Paul M , Pockley A. Graham , Ball Graham , Ellis Ian O. , Rakhah Emad , Hodi Zsolt , Lee Andrew , Chan Arlene , Chan Stephen 
Published: May 2019

590 Background: We hereby evaluated the histopathological and radiological alterations of tumor characteristics after receiving NACT and the clinical significance of the changes of adjuvant therapy based on these findings. Methods: A pathological assessment of tumor features including ER, PR, HER2 and proliferation markers (Ki67 and SPAG5) status in pre and post NACT tumors tissue have been centrally evaluated in two cohorts [Nottingham University Hospital (NUH; n=850) and Australian cohort (n=250 patients)]. Since 2013 any change in the ER and HER2 status from negative (-) [in the pre NACT biopsies] to positive (+) [in the post NACT surgical specimens] received additional adjuvant therapy (Endocrine therapy (ET) for ER+ and Trastuzumab for HER2+ cases) in NUH. MRI volumetric and texture changes have been assessed in 400 cases. The primary end point was disease free survival (DFS; median follow-up = 62 months). Results: 10% of pre NACT HER2- cases had been converted to post NACT HER2+ and those cases who subsequently received adjuvant Trastuzumab had achieved 92% 5-year DFS compared to those who remained HER- in post NACT specimens (58% 5-year DFS); (HR (95% CI)= 0.25 (0.08-0.80); p=0.016). While 13% of pre NACT HER2+ tumors were converted into HER2- in post NACT surgical specimens and had similar 5-year DFS to those who remained post NACT HER2+ (5-year DFS= 94% vs., 87%; p=0.613). Loss of PR in the residual disease of pre NACT ER+ BC was associated with shorter 5-year DFS after ET compared to those who remained post NACT PR+ (HR (95% CI)=2.1 (1.25-3.46); p=0.005). After NACT, 40% of pre NACT SPAG5+ cases were converted into post NACT SPAG5- and these patients had prolonged DFS compared to those who remained SPAG5+ in post NACT specimens (27%) [5-year DFS=84% vs 49%; (HR (95% CI)= 3.8 (2.1-6.9); p<0.0001). A prognostic model has been generated including factors in table (AUC = 0.854 (95% CI) = 0.777-.0.931; p= 0.00000001]. Conclusions: We hereby showed evidences a change of treatment strategy based on the changes in the tumor post NACT phenotype gives the optimal choice of treatment eg., the introduction of HER2 targeting therapy for the conversion of HER2– to HER2+ phenotype after NACT improved DFS. Multivariate Cox regression model for 5-year DFS. [Table: see text]
CALGB (Alliance) 40603: Long-term outcomes (LTOs) after neoadjuvant chemotherapy (NACT) +/- carboplatin (Cb) and bevacizumab (Bev) in triple-negative breast cancer (TNBC).
Authors: Sikov William M. , Polley Mei-Yin , Twohy Erin , Perou Charles M. , Singh Baljit , Berry Donald A. , Tolaney Sara M. , Somlo George , Port Elisa R. , Ma Cynthia X. , Kuzma Charles S. , Mamounas Eleftherios P. , Golshan Mehra , Bellon Jennifer Ruth , Collyar Deborah E. , Hahn Olwen Mary , Hudis Clifford A. , Winer Eric P. , Partridge Ann H. , Carey Lisa A. 
Published: May 2019

591 Background: Both Cb and Bev demonstrate activity when combined with standard chemotherapy in TNBC. CALGB 40603 is a 2x2 randomized trial that previously demonstrated that adding Cb to NACT significantly increased pathologic complete responses in the breast/axilla (pCR), while adding Bev did not (Sikov, JCO 2015). Here we report 5-year LTOs and assess factors that influenced them. Methods: 443 patients with clinical stage II-III previously untreated TNBC received 12 weeks of paclitaxel (wP) +/- Cb then dose-dense AC, +/- Bev before surgery. The primary endpoint was pCR. Analyses of LTOs (event-free survival (EFS), distant recurrence-free interval (DRFI) and overall survival (OS)), impact of residual cancer burden and other variables were secondary. Results: Median follow-up was 5.7 years (y); 5y EFS was 70.9% (95% CI; 66.7%-75.4%), DRFI 76.3% (72.3%-80.5%) and OS 76.9% (72.9%-81.2%). Pretreatment clinical stage and achieving pCR correlated with LTOs, while age, race, subtype (basal-like vs. not) and tumor grade did not. Among pCR 5y EFS was 86.4% vs. 57.5% for non-pCR (HR 0.28, 0.19-0.43), OS was 88.7% vs 66.5% (HR = 0.28, 0.17-0.44). This relationship was similar in all trial arms. Any residual disease conferred poorer outcome; compared with pCR/Residual Cancer Burden (RCB) 0, EFS HRs were 2.29 (1.32-3.97), 3.01 (1.90-4.74), and 9.67 (5.66-16.51) for RCBI, II and III, respectively. There were no improvements in LTOs with Cb (EFS HR 0.99, 0.70-1.40) or Bev (EFS HR 0.91, 0.64-1.29). In an exploratory analysis, receipt of ≥11 doses of wP was associated with better EFS (HR 1.92, 1.33-2.77); this was particularly notable in Cb-treated arms. Conclusions: As expected, regardless of treatment arm pCR was associated with markedly better LTOs, and pts with any residual disease had significantly worse outcomes. The addition of Cb or Bev to standard NACT for TNBC did not improve LTOs in this trial, although it should be noted that the trial was not powered for this endpoint. Omission of chemotherapy doses may result in poorer outcomes, especially among Cb-treated pts, which may warrant further evaluation. Support: U10CA180821; U10CA180882; Genentech; https://acknowledgments.alliancefound.org ; NCT00861705 Clinical trial information: NCT00861705.
Preoperative checkpoint inhibition (CPI) and cryoablation (Cryo) in women with early-stage breast cancer (ESBC).
Authors: Comen Elizabeth Anne , Bryce Yolanda , Page David B. , Solomon Stephen Barnett , Rodine Micaela , Abaya Christina DiLauro , Morris Elizabeth Anne , Plitas George , El-Tamer Mahmoud , Gemignani Mary , Sclafani Lisa M. , Morrow Monica , Brogi Edi , Patil Sujata , Ho Teresa , Wong Phillip , Budhu Sadna , Merghoub Taha , Norton Larry , McArthur Heather L. 
Published: May 2019

592 Background: Checkpoint inhibition (CPI) combined with local strategies that cause local tumor destruction, such as cryo may augment tumor specific immunity and improve survival. We previously demonstrated in 18 ESBC patients (pts) that pre-operative (pre-op) cryo with ipilimumab (ipi) is not only safe but also generates robust local and systemic immune responses (NCT01502592). Given the added activity of dual CPI in other tumors, we undertook a second pilot study of pre-op ipi/nivolumab (nivo)/cryo to confirm the safety of this combination and the impact on immune biomarkers. Methods: In both pilot studies, eligible pts had operable ≥1.5cm invasive HER2 negative ESBC. CPI was administered 8-15d prior to, and cryo was performed 7-10d prior to, standard-of-care (SOC) surgery. Toxicity evaluation continued for 12wks after drug administration. Blood for immune correlates was obtained at baseline, cryo, surgery and 2-4 weeks thereafter. Tumor samples were obtained at cryo and surgery. Flow-cytometry of peripheral lymphocytes was compared to previously reported ipi/cryo responses. Results: After a median follow-up of 66 months all 18 ESBC ipi/cryo pts, including 3 TNBC pts, are recurrence free. In the ipi/nivo/cryo study, the safety primary endpoint was met when 5 pts underwent SOC surgery without delay. Ipi/nivo/cryo was well tolerated overall. One pt on an aromatase inhibitor had grade 4 liver toxicity 8 weeks after surgery. One pt, 3 weeks after her SOC surgery, developed grade 1 hyperthyroidism, preventing a secondary axillary dissection from proceeding as scheduled. Robust activation of peripheral CD4+ and CD8+ T cells peaked at week 2 post ipi/nivo with the majority of activated CD8+ T cells expressing PD1. Comparing the correlatives of the ipi/nivo/cryo study with the prior ipi/cryo study, we observed higher expression of activation markers (Ki-67, ICOS, CTLA-4, LAG-3) on peripheral T cells and downregulation of suppressor cells. Conclusions: Ipi/cryo-treated pts, including 3 TNBC pts, remain recurrence free after > 5y. Combining cryo with ipi/nivo preop is feasible, safe, and associated with greater T cell activation than ipi/cryo alone. These results informed an ongoing randomized phase 2 study of pre-op ipi/nivo/cryo versus SOC in women with residual TNBC after neoadjuvant chemotherapy (NCT03546686). Clinical trial information: NCT02833233.
Checkpoint inhibitors assessment in oropharynx cancer (CIAO): Safety and interim results.
Authors: Ferrarotto Renata , Bell Diana , Rubin M. Laura , Lee J. Jack , Johnson Jason Michael , Goepfert Ryan , Phan Jack , Elamin Yasir , Myers Jeffrey , Hessel Amy Clark , Johnson Faye M. , Gillison Maura L. , Sikora Andrew G. , Glisson Bonnie S. , Gross Neil D. 
Published: May 2019

6008 Background: Anti-PD-1/PD-L1 are active in metastatic oropharynx squamous cell carcinoma (OPC). Durvalumab (durva) and tremelimumab (tremi) target respectively PD-L1 and CTLA-4, which in combination may be synergistic. Here we report the safety and interim results of durva vs. durva+tremi prior to surgery in a window of opportunity trial in OPC. Methods: Pts were randomized 1:1 to durva 1500 mg or durva 1500 mg + tremi 75 mg IV Q4W x 2 cycles. The primary objective was to quantify pre- and post-treatment differences in CD8+ tumor infiltrating lymphocytes for the two arms. Secondary objectives included safety, toxicity, ORR by RECIST, fraction of patients undergoing surgery at 8 wks, and percentage viable tumor cells in the surgical specimen. Serial pre- and post-treatment blood and tumor specimens were collected for ongoing correlative analyses. Results: 28 pts enrolled: median age 64y, 27 (96%) male, 19 (68%) newly diagnosed, most (63%) at stage IVA (AJCC 7th Ed), 9 (32%) had locoregional recurrence, 24 (86%) p16 positive, and 22 (79%) had ≤ 10 PPY smoking history. Median follow-up was 7.6 months. The most common AEs were fatigue (36%), leukopenia/lymphopenia (25%), transaminitis (25%), and rash (21%). Grade 3 AEs occurred in 4 (14%) pts: 2 elevated lipase, 1 diarrhea, and 1 hepatitis, all were manageable. There were no grade >3 AEs. ORR was 43%: 50% had SD (including 29% tumor shrinkage in 1 pt). Treatment effect in the surgical specimen was observed in 19 (79%) of 24 evaluable pts; 2 pts had major pathologic response (≤ 10% viable tumor) at the primary site. Efficacy was equivalent in both arms. The 2 pts with PD and 1 pt with SD were switched to chemotherapy after durva +/- tremi before resection; interestingly, each achieved a pCR in the primary. Most pts (57%) didn’t receive radiotherapy after surgery. There was a statistically significant association between ORR and treatment effect (p=0.014). The median percentage of viable tumor in the primary was 37.5% in pts with PR, and 82.5% in SD (p=0.003). Conclusions: Durva +/- tremi prior to surgery was well tolerated in OPC pts. Activity is encouraging with treatment effect seen in 79% of pts. The primary endpoint and complete efficacy data will be presented. Clinical trial information: NCT03144778.
Genomic and transcriptomic landscape of oral pre-cancers (OPCs) and risk of oral cancer (OC).
Authors: William William Nassib , Lee Won-Chul , Lee J. Jack , Lin Heather Y. , Eterovic Agda Karina , El-Naggar Adel K. , Gillenwater Ann M. , Pisegna Marlese , Tong Pan , Li Lerong , Tian Xianjun , Tran Hai T. , Saintigny Pierre , Wang Jing , Papadimitrakopoulou Vassiliki , Lippman Scott Michael , Futreal Phillip Andrew , Heymach John , Zhang Jianjun 
Published: May 2019

6009 Background: The molecular landscape of OPCs and its association with neoplastic progression is largely unknown. We report the results of high throughput DNA/RNA profiling of OPCs from pts in the Erlotinib Prevention of Oral Cancer trial (EPOC), with long-term prospective follow-up. Methods: We performed next generation sequencing of 201 cancer genes (MD Anderson T200 platform) in 170 OPCs from EPOC, and RNA profiling using HTG EdgeSeq Oncology Biomarker Panel containing 2,560 transcripts in a subset of 141 OPCs. 73 pts developed invasive OC during a median follow up of 7.3 years, from whom 23 paired OCs were profiled to characterize the evolutionary trajectory from OPCs to OCs. OPC molecular features were correlated with OC-free survival. Results were compared with TCGA invasive OC DNA/RNA profiles and an independent set of 86 OPCs with RNA data. Results: Similar to TCGA, C > T was the predominant substitution. The top mutated genes in OPCs were TP53 (29%), CDKN2A (15%), NOTCH1 (11%) and PIK3CA (7%), which were also frequently mutated (albeit at higher rates) in OCs from EPOC or TCGA. There was a progressive increase of tumor mutation burden (TMB, P < 0.05) and frequency of high-risk TP53 mutations (P = 0.02) from hyperplasia, to dysplasia, to invasive OCs (P < 0.05). Median TMB was higher in OPCs from pts who developed OC (2.45 mut/Mb) vs those who did not (1.22 mut/Mb) (P < 0.01). Pts with TP53 mutated OPCs had shorter OC-free survival compared to TP53 wild-type (HR 1.81, 95% CI 1.13-2.90, P = 0.01). A prognostic score was derived from a Cox regression model which identified 12 mRNA transcripts associated with OC risk (HR 4.72, 95% CI 2.51-8.86, P < 0.01), and which was validated in the independent set of 86 OPCs (HR 2.68, P < 0.01). This score was also associated with shorter overall survival when applied to invasive OCs from TCGA pts (HR 2.72, P < 0.01). Conclusions: This is the first large-scale cohort of OPC pts with long-term, prospective follow up and comprehensive RNA/DNA profiling. We demonstrated an association between TMB, TP53 mutations, a 12-gene RNA signature score in OPCs, and OC risk. This study may provide a framework for similar efforts of pre-cancer molecular profiling in the oral cavity and other sites, such as the PreCancer Atlas of the NCI.
PIK3CA mutation as a prognostic factor in HPV-associated oropharynx cancer.
Authors: Beaty Brian T. , Gupta Gaorav , Shen Colette J. , Amdur Robert J , Weiss Jared , Grilley-Olson Juneko E. , Patel Shetal Arvind , Zanation Adam M. , Hackman Trevor , Thorp Brian , Blumberg Jeffrey , Patel Samip , Weissler Mark Christian , Yarbrough Wendell Gray , Sheets Nathan Christopher , Parker Joel S. , Hayes Neil , Mendenhall William M. , Dagan Roi , Chera Bhishamjit S. 
Published: May 2019

6011 Background: PIK3CA is the most frequently mutated gene in HPV-associated oropharyngeal SCC (OPSCC), with a prevalence of 20-30%. While PIK3CA mutations have been associated with adverse outcomes in cervical cancer, their prognostic significance in HPV-associated OPSCC remains unknown. We sought to elucidate the significance of PIK3CA mutations in a prospective cohort of HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Methods: Seventy-eight patients with HPV-associated OPSCC were prospectively enrolled on three protocols: LCCC 1121 (NCT03161821) or two phase II clinical trials of de-intensified CRT (NCT02281955 / NCT03077243). De-intensified regimen was 60 Gy IMRT with concurrent cisplatin (30mg/m2). Next-generation sequencing of tumor samples was performed using a targeted panel-based assay (UNCSeq), including over 200 genes. We estimated disease-free survival (DFS) using the Kaplan-Meier method and compared treatment groups with two-sided log-rank test (Medcalc). Results: Sequencing was performed in 78 patients with a median follow-up of 24 months. Seventy-five patients received 60Gy; three patients received 70Gy. Ten patients had disease recurrence (2 regional only, 5 distant only, 3 regional and distant). Thirty-eight of 78 patients had at least one mutation identified (17 PIK3CA, 4 PTEN, 3 KRAS, 3 FBXW7, 3 FGFR3, 2 TP53, 2 prothrombin 20210, 1 NRAS, 1 BRCA1, 1 factor V Leiden, 1 FLT3, 1 RAD50, 1 PIK3R1). The most common site of PIK3CA mutation was the helical domain (E545K – 8/17, E542K – 2/17). Despite similar T/N staging and tobacco pack years, patients with WT-PIK3CA had significantly higher DFS (93%) compared with 65% for patients with PIK3CA mutations (p = 0.0009). Patients with mutations other than PIK3CA also had improved DFS relative to those with PIK3CA mutations (96% vs. 65%; p = 0.0147). Conclusions: PIK3CA mutation is associated with worse DFS in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with definitive CRT. These findings suggest that patients with PIK3CA mutations may not be suitable for de-intensified therapy and investigation of novel treatment strategies may be appropriate.
Anlotinib treatment in locally advanced or metastatic medullary thyroid carcinoma: A multicenter, randomized, double-blind, placebo-controlled phase IIB trial.
Authors: Li Dapeng , Tang Ping Zhang , Chen Xiaohong , Ge Minghua , Zhang Yuan , Guo Zhuming , Wang Jun , Shi Feng , Zhang Jiewu , Cheng Ying , Li Zhendong , Liu Hui , Qin Jianwu , Huang Rui , Cheng Ruochuan , Xu Zhengang , Chi Yihebali , Zheng Xiangqian , Gao Ming 
Published: May 2019

6019 Background: Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferative signaling. Our previous single-arm phase 2 ALTN/MTC trial (NCT01874873) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in locally advanced or metastatic medullary thyroid carcinoma (MTC). Here we report results of the phase IIB trial (ALTER01031, NCT02586350) of anlotinib for locally advanced or metastatic MTC with a larger samples. Methods: Between September 2015 and September 2018, 91 patients were enrolled in China. Eligible patients have diagnosed as phase IV MTC with relapsed and measurable disease and without antiangiogenetic target therapy. The patients were randomly assigned in a 2:1 ratio to receive anlotinib or a matched placebo (12 mg QD from day 1 to 14 of a 21-day cycle). Patients who have been diagnosed with disease progression by the Independent Imaging Committee could be unblinded and crossed to the treatment group if the patient previous treated by placebo. The primary endpoint was progression-free survival (PFS). Results: 91 patients were randomized 62 to anlotinib arm and 29 to placebo arm. Until the data cutoff date (1 Feb 2019), median PFS was 20.67 months (95%CI, 14.03-34.63) in anlotinib arm vs 11.07 (95%CI, 5.82-14.32) months in placebo arm (HR 0.53, p = 0.0289). The OS data were not sufficiently mature for analysis. Considerable improvement in ORR was observed over the two arms (48.39% vs 3.45%, p < 0.0001). The adverse events (AEs) were 100% in anlotinib arm and 89.66% in placebo arm. The most common AEs in anlotinib arm were hand-foot syndrome, hypertension, hypertriglyceridemia and diarrhea. Conclusion: ALTER01031 met its primary endpoint of PFS shows that anlotinib treatment is effective and well tolerated. The safety profile was consistent and no new adverse events were identified. These data potentially extend the role of anlotinib monotherapy as a new therapy strategy for MTC patients. Clinical trial information: NCT02586350.
Induction chemotherapy with docetaxel, cisplatin and cetuximab versus docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy with cetuximab for locally advanced or inoperable squamous cell carcinoma of the head and neck: Promising results of a randomized phase II AGMT-trial.
Authors: Keil Felix , Hartl Maximilian , Altorjai Gabriela , Pecherstorfer Martin , Mayrbäurl Beate , de Vries Alexander , Berghold Andrea , Riedl Regina , Fridrik Michael A. , Fuereder Thorsten , Burian Martin , Greil Richard 
Published: May 2019

6027 Background: Induction chemotherapy (ICT) with Cisplatin (P), 5-FU (F) and Taxanes (T) is a therapeutical option in patients suffering from locally advanced or unresectable stage III or IV squamous cell carcinoma of the head and neck (SCCHN). The role of ICT is controversial and toxicity and/or delay of radiotherapy may reduce the potential benefit of this treatment regimen. Here we report promising results of a randomized phase II trial comparing TPF with TP and Cetuximab (C) replacing F. Methods: In our trial, N= 100 patients with locally advanced or unresectable stage III or IV SCCHN were randomly assigned to either Arm A ( N= 49), receiving TPF, or Arm B ( N= 51), receiving TPC, both followed by radiotherapy (RT) + C. The primary end-point of the study was overall response rate (ORR) three months after RT + C was finished. Results: We observed a remarkable response rate (CR + PR) of 86.4% in the TPC-arm that compared favorably with 77.5% responding patients in the TPF-arm three months after RT + C was completed. OS and PFS were similar in both arms. After 400 days we observed an OS rate of 79% in the TPF and 86% in the TPC arm, and a PFS rate of 67% in the TPF and 70% in the TPC arm. TPC containing ICT led to less serious adverse events (SAEs), including blood and lymphatic disorders (40.8% in TPF arm, 27.5% in TPC arm) and metabolism and nutrition disorders (22.4% in TPF arm, 9.8% in TPC arm) during ICT. Interestingly, in HPVp16 positive patients, 88.24% in the TPF-arm and 93.33% in the TPC-arm showed CR or PR three months after RT + C, whereas only 69.57% in the TPF-arm and 82.76% in the TPC-arm showed CR or PR. We only lost one patient because of treatment-related mortality (TRM) and no delay from the end of ICT to local radiotherapy was observed in any patient. All patients received RT + C within three weeks after ICT was completed. Conclusions: In conclusion, TPC is a feasible and tolerable therapy regimen and can be applied within one day with less hematological toxicities. In contrast, more local reactions were observed after TPC. TPC containing ICT leads to improved response rates, while OS and PFS were similar in both arms. TRM was extremely low with 1%. Therefore, we conclude, that TPC containing ICT could be a considerable therapeutical alternative for patients with locally advanced or unresectable stage III or IV SCCHN, who are eligible for ICT. Clinical trial information: 2011-005540-99.