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Well-designed randomized trials provide the highest level of scientific evidence to guide clinical decision making. In chemoradiotherapy of locally advanced squamous cell carcinoma of the head and neck (SCCHN), data support the use of three cycles of 100 mg/m(2) cisplatin given every 3 weeks concurrently with conventionally fractionated external beam radiotherapy, although a full compliance with all three cycles is reserved to only about two thirds of initially eligible cases. On an individual patient level, practicing oncologists have to determine whether the patient is a suitable candidate for this treatment or whether contraindications exist. In the latter case, an adequate alternative has to be offered. In this regard, to facilitate triaging of medical information, we reviewed available publications on this topic and prepared practice-oriented recommendations for systemic treatment concurrent to definitive and post-operative radiotherapy. Even if no contraindications for the standard-of-care cisplatin apply, clinicians may opt for alternative regimens by adjusting the peak dose, cumulative dose, or timing of cisplatin. Relative contraindications pose the major issue in clinical practice, as very limited data is available in the literature and final decisions are usually based on an expert opinion or retrospective cohort studies. In the case of absolute interdiction of cisplatin, several alternative regimens incorporating carboplatin, 5-fluorouracil, cetuximab, and docetaxel are available. At the same time, it should be kept in mind that radiotherapy alone represents a viable option with hyperfractionation being particularly beneficial in the definitive management of limited nodal disease. Ideally, all treatment propositions should be discussed within multidisciplinary tumor boards taking into account the patient- and disease-related characteristics as well as local logistics and reimbursement policies.

Immune checkpoint inhibitors are now standard-of-care treatments for metastatic cutaneous melanoma. However, for rare sub-groups, such as mucosal melanomas, few published data are available, and with no established therapeutic guidelines. Our objective was to assess the response to anti-CTLA4 and anti-PD1 immunotherapy in patients with mucosal melanomas. We performed a single-center, prospective cohort analysis of patients with non-surgical locally advanced and/or metastatic mucosal melanoma receiving anti-CTLA4 and/or anti-PD1 immunotherapy from 2010 to 2016. Forty-four patients were enrolled, including 18 (40.9%) with head and neck, 12 (27.3%) with vulvo-vaginal and 14 (31.8%) with ano-rectal primary tumours. Eleven (25%) patients had stage 3 disease, and 11 (25%) had distant metastases. The first-line immunotherapy was ipilimumab in 24 patients and pembrolizumab in 20. The objective response rate (ORR) was 8.2% (one complete response) for ipilimumab and 35% (four complete responses) for pembrolizumab. No significant difference was observed for primary tumour location. The median follow-up was 24 months (range 4–73). The median progression-free survival (PFS) in the first-line ipilimumab and pembrolizumab groups was 3 months [95% confidence interval (CI) 2.5–4.6] and 5 months (95% CI 2.6–33.1), respectively (p = 0.0147). In the patients with unresectable and/or metastatic mucosal melanoma, we found ORR and PFS rates comparable to those in patients with cutaneous melanoma, with no significant differences in the types of mucosal surfaces involved. Anti-PD1 therapy has a more favorable benefit-risk ratio than ipilimumab and should be used preferentially.

664 Background: Digestive and non-digestive cancers in patients with inflammatory bowel disease (IBD) are potentially sensitive to bevacizumab-based chemotherapy. Previous reports have suggested an increased toxicity in IBD patients receiving anti-VEGF agents. The safety of bevacizumab in this population is poorly documented. Methods: A retrospective review of records of patients with IBD treated with bevacizumab-containing chemotherapy for metastatic solid tumors in Gustave Roussy hospital between 2007 and 2016. Results: Twenty eight patients (median age 43, range: 23-73) with a past history of IBD (6 ulcerative colitis, 22 Crohn’s disease) were identified. IBD was considered severe in four pts (13%). Patients presented a good control of IBD symptoms with a median number of 0 (range: 0-2) disease flares during the two years before bevacizumab initiation. Three patients were receiving corticosteroids, and another four were receiving mesalazine for IBD. No patient had abscess, fistula or hemorrhage at the time of bevacizumab initiation. The treated cancer was: colon (n = 8), rectum (n = 5), small bowel (n = 5), NSCLC (n = 4), ovary (n = 1), breast (n = 3) and other (n = 2). Patients received chemotherapy [5-FU-based (LV5FU2, FOLFOX or FOLFIRI) in 17, oxaliplatin in 7, irinotecan in 8, taxanes in 7] with bevacizumab given at the approved dose-intensities of 2.5 mg/kg/week (19 pts) or 5 mg/kg/week (7 pts). Records of chemotherapy from 2 patients were missing. A median number of 8 cycles of bevacizumab(range: 2-39) was given concomitantly to chemotherapy and then as maintenance therapy, with the following grade ≥2 toxicities: hypertension in 6 cases (20%) and proteinuria in 3 cases (10%). No dose-limiting toxicity was observed. No change in IBD treatment was required. One patient developed grade 2 rectorragia (identified as Crohn’s disease flare-up) after 6 months of bevacizumab+ FOLFIRI. After withdrawal of irinotecan, the patient was re-challenged with bevacizumab for another 6 cycles without recurrence of bleeding. Conclusions: In our experience, bevacizumab can be given to cancer patients with quiescent IBD at conventional doses with good clinical tolerance.

e21517Background: Immune-checkpoint inhibitors improved significantly the outcomes of metastatic cutaneous melanoma. For rare sub-groups such as mucosal melanomas, only few published data are avail...

6015Background: Immune checkpoint inhibitors (ICI) have shown efficacy in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) with an overall response rate (...

Background Cetuximab is crucial in the management of squamous cell carcinoma of the head and neck of patients. Grade 3–4 cetuximab-induced infusion reactions (CI-IRs) occur in 2% of patients with colorectal cancer. Despite the 2.7% CI-IR rate in the EXTREME trial, higher rates were reported in small series of patients with head and neck squamous cell carcinoma (HNSCC) (6%–18%). There is an urgent need to better appraise the natural history and the predictive factors for CI-IRs in patients with HNSCC exposed to cetuximab. Methods The medical records from patients with HNSCC (n=428) treated by cetuximab at Gustave Roussy from January 2013 to December 2015 were reviewed. The impact of potential risk factors was analysed. Results Out of 428 patients, 24 patients (5.4%) presented CI-IR, including grade 3–4 (95.7%); about 21% (5/24) requiring intensive care unit referral and quasi all occurred within the first cycle (21/24). In a multivariate analysis, the occurrence of grade 3–4 CI-IR was associated with tobacco and alcohol history (p=8.5e–3) and with prior allergy history (p=2.9e–3). CI-IRs tended to be associated with poor overall survival in patients with recurrent and metastatic HNSCC and with a higher number of further lines of chemotherapy. Conclusion In real life, CI-IRs appear far more common in patients with HNSCC (5.4%) than reported in prospective trials. This is the largest series of patients ever focusing on the risk of CI-IR in patients with HNSCC. Prior allergy history and tobacco history are associated with CI-IR and could be used to better allocate treatment. Further prospective data are required to confirm these findings.