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6007 Background: Inhibition of the PD-1/PD-L1 pathway is efficient in recurrent/metastatic HNSCC. Targeting the immune checkpoint CTLA-4 may be synergistic to radiotherapy. This trial studies feasibility and efficacy of combined PD-L1/CTLA-4 blockade concomitant to induction chemotherapy and radiotherapy. Methods: Patients with previously untreated stage III-IVB (AJCC 8th edition) HNSCC were eligible for this multicenter phase II trial. Treatment consisted of a single cycle of cisplatin 30mg/m² d1-3, docetaxel 75mg/m² d1, durvalumab 1500mg fix dose d5 and tremelimumab 75mg fix dose d5. Patients with at least 20% increase of intratumoral CD8+ immune cell density or pathological complete response (pCR) in the re-biopsy (performed on d22-26) entered radio-immunotherapy (RIT) up to a total dose of 70Gy. Patients received further three cycles of durvalumab/tremelimumab (q4w, two concomitant and one subsequent) followed by eight cycles of durvalumab mono (q4w). Primary endpoint was a feasibility rate of patients entering RIT to receive treatment until at least cycle 6 of immunotherapy of ≥80% (i.e. dose limiting toxicity/DLT ≤20%; exclusion of patients with other reasons than DLT for treatment discontinuation; feasibility unacceptable if ≤65%). The calculated sample size was 57 patients to enter RIT. Main secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Between Sep 2018 and Mai 2020, 80 patients were enrolled (one excluded). Median age was 60 years, 33 patients (42%) were current smokers, 43 patients (54%) had oropharyngeal tumors (53% p16 positive), 44 patients (56%) were stage IV. Median follow up was 12.5 months. After induction chemo-immunotherapy 41 patients had pCR and 31 an intratumoral CD8+ immune cell increase. Of 60 patients entering RIT (primary endpoint cohort), 10 received DLT and 4 discontinued for other reasons. The feasibility rate of the RIT cohort until cycle 6 was 82%, meeting the primary endpoint of ≥80% (95% confidence interval (CI), one-sided (lower boundary): 72%). The RIT cohort had a PFS rate at 1 year of 79% (CI 69-90%) and at 2 years of 73% (CI 61-87%) and an OS rate at 1 year of 89% (CI 81-98%) and at 2 years of 86% (CI 77-97%). The entire study cohort had a PFS rate at 1 year of 75% (CI 65-85%) and at 2 years of 68% (CI 58-81%) and an OS rate at 1 year of 86% (CI 78-95%) and at 2 years of 80% (CI 70-91%). Toxicity (treatment-related or un-related) ≥grade 3 appeared in 75 patients (95%) and mainly consisted of dysphagia (53%), leucopenia (48%) and infections (29%). DLT mainly consisted of hepatitis (10%). Conclusions: The trial met the primary endpoint feasibility. CD8+ T cell-based pathological patient selection after induction therapy identifies patients with promising PFS rates after chemotherapy-free RIT. Clinical trial information: nct03426657.

6519 Background: PD-1/PD-L1 inhibitors are efficient in head and neck squamous cell cancer (HNSCC). Combination with anti-CTLA4 agents may enhance anti-tumor activity compared to anti-PD-1/PD-L1 monotherapy in different tumor types. In the CheckRad-CD8 trial the typical induction treatment consisting of Cisplatin/Docetaxel was combined with Durvalumab/Tremelimumab. Patients with pathological complete response (pCR) in the re-biopsy after induction treatment or at least 20% increase of intratumoral CD8 density in the re-biopsy compared to baseline entered radioimmunotherapy with concomitant Durvalumab/Tremelimumab. Methods: In this prospective multicenter phase II trial, patients with HNSCC stage III-IVB received a single cycle of Cisplatin 30mg/m² d1-3, Docetaxel 75mg/m² d1, Durvalumab 1500mg fix dose d5 and Tremelimumab 75mg fix dose d5. Objectives of this interim analysis were to quantify the effect of the induction treatment on intratumoral CD8 density and the pCR rate and to generate safety data. Results: Between Sep 2018 and Dec 2019, 57 patients were enrolled. Median age was 59 years, 22 patients (37%) were current smokers, 27 patients (47%) had oropharyngeal tumors (52% p16 positive). The median pre-treatment intratumoral CD8 density was 335 CD8+ cells/mm². After induction treatment 27 patients (47%) had a pCR in the re-biopsy and further 25 patients (44%) had a relevant increase of intratumoral CD8+ cells (median increase by factor 3.0). Response according to RECIST criteria was CR in 1 (2%), PR in 19 (33%) and SD in 20 patients (35%) (17 patients not evaluable). Adverse events (AE) grade 3-4 appeared in 39 patients (68%) and mainly consisted of leucopenia (43%) and infections (28%). 6 patients (11%) developed grade 3-4 immune-related AEs. In multivariable analysis the intratumoral CD8 density was the only independently significant predictor of pCR (odds ratio 1.0013 per cell/mm², 95%-CI 1.00023-1.0023, p=0.017). 42 patients (74%) continued with Durvalumab/ Tremelimumab concomitant to radiotherapy. Conclusions: Single cycle induction treatment with Cisplatin/Docetaxel/Durvalumab/Tremelimumab is feasible and achieves a high pCR rate. CD8 density may have a predictive role for further treatment planning in locally advanced HNSCC. Clinical trial information: NCT03426657 .

6035Background: TPF induction chemotherapy (IC) is a reasonable treatment for locally advanced (LA) squamous cell carcinoma (SCC) of the head and neck. Substantial toxicity may compromise complianc...

e17042 Background: TPF induction chemotherapy (IC) is a reasonable treatment option for locally advanced (LA) squamous cell carcinoma (SCC) of the head and neck (HN). However, substantial toxicity ...

6077 Background: To report the mature data of a prospective phase II-trial to investigate the feasibility, efficacy and safety of combination therapy with Cis, Cet and HART in LA SCCHN. Methods: Patients (pts) with stage III or IV, M0 SCCHN were enrolled and treated with an initial dose of Cet (400 mg/m2), followed by weekly dose of 250 mg/m² before HART, which started with a prescribed dosage of 2.0 Gy per day for three weeks followed by 1.4 Gy twice daily to a total dosage of 70.6 Gy to the gross tumor volume. Cis 40 mg/m² was administered weekly for 6 weeks. Results: From February 2007 through November 2010, 74 pts were enrolled, 68 pts with a median age of 56 years (range 37 to 69 years) were evaluable. 50% had oropharyngeal SCC. Of these, 65 pts (96%) received > 90% RT dosage, 50 pts (74%) > 90% Cet dosage and 56 pts (82%) > 4 cycles Cis 40 mg/m². 3D-CRT was used in 72% and 28 patients are currently still being followed up. The most common grade >3 toxicities were mucositis (59%) and dysphagia (52%). Cet-related grade >2- toxicities included dermatitis (15%) within the radiotherapy portals. Nine (14%) pts were missing for response evaluation (e.g. withdrawal of consent). Complete remission rate [(p)CR] was observed in 23/68 (34%) including with 16 pts (24%) who reached a CR of the primary tumor but a selective lymph node dissection was performed 6-8 weeks after end of radiation treatment for residual neck disease. Furthermore, partial remission (PR) was achieved in 29/68 (43%), so an overall response (OR) of 52/68 (77%) was reached. No change/stable disease occurred in 3/68 pts (4%), progressive disease (PD) occurred in 1 pt (1%) and 3 pts (4%) have died due to disease progression. The 2-year overall survival and disease-free survival were 64.2% and 45.3%, respectively. Conclusions: Combination therapy of LA SCCHN consisting of HART-Cis-Cet is an highly active regimen. The addition of Cet to weekly Cis and daily RT was well tolerated and resulted in encouraging local disease control and survival rates. Clinical trial information: 2005-000355-15.

5512 Background: Are 6 cycles of once weekly DDP plus one cycle of 5-FU with concurrent HART superior to 2 cycles of MMC plus one cycle of 5-FU in terms of overall survival (OS) and metastases-free survival (MFS)? Methods: Eligibility: Stage IV SCC of oro(OP)- and hypopharynx(HP), KFS of ≥80% stratified for sites, N-status, grading, hemoglobin and center. The HART schedule was reported elsewhere (V.Budach, JCO 23;2005). HART was applied concurrently with DDP/5-FU at 30mg/m² days 1,8,15,22,29,36 or MMC/5-FU at 10mg/m2 day 1+36 and for both arms with 600mg/m² 5-FU days 1-5 as 120 hrs. c.i. TVD dose prescription was 72 Gy using 3D-conformal or IMRT-TP. 364 patients were analysed using an ITT principle for OS, MFS, progression-free survival (PFS) and loco-regional control (LRC). Hazard ratio (HR) calculations were adjusted for competing risk factors. Results: Median follow-up was 48 mos. for both arms. Mean age was 55.4 years, 83/17% were male/female and 100% stage IV patients (UICC 2002). 58.5%/41.5% of all patients suffered from OP- or HP cancer, respectively. The OS and MFS at 4 years for the DDP- versus MMC-arm was 42.1% vs. 38.8% (n.s.) and 67.3% vs. 56.6% (p=.05), respectively. The LRC and PFS for the DDP versus MMC-arm was 58.6% vs. 57.2% (n.s.) and 46.4% vs. 38.7% (n.s.). Seven items recorded for acute toxicity and 9 for late morbidity showed no significant differences between the treatment arms except for creatinine for the DDP-arm (p < 0.001) using nonparametric analyses of variances for repeated measurements. The overall compliance rates for RTX were 96%, DDP: 72%, 5-FU: 97%, MMC: 86%, respectively. Conclusions: This phase III trial first establishes level IB-evidence for a once weekly DDP chemoradiation regimen. For MFS at 4 yrs., DDP/5 FU-HART is superior to MMC/5 FU HART at equal levels of acute and late radiation sequelae for both treatment arms. No significant differences were seen yet for OS, PFS or LRC. Chemoradiation with weekly DDP/5-FU or MMC/5-FU shows excellent compliance rates and can easily compete with other concurrent chemo- or bio-radiation schedules including induction TPF followed by radiation.