Concomitant Cetuximab Research Articles

Stereotactic reirradiation in the treatment of head and neck cancers: A retrospective study on the long-term experience of the Oscar Lambret Center

Background and purposeStereotactic radiotherapy potentially treats unresectable recurrences of previously irradiated head and neck (H&N) cancer. This study aimed to assess its efficacy and safety and evaluate prognostic factors. Materials and methodsWe conducted a large retrospective series that included 110 patients who had undergone 36-Gy, six-fraction stereotactic reirradiation (CyberKnife®) for recurrent/secondary H&N cancer between 2007 and 2020 at the Oscar Lambret Center. Patient characteristics and toxicities were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. ResultsMedian follow-up time was 106.3 months. The 2-year OS rate was 43.8 % (95 % confidence interval, 95 % CI, 34.3–52.9) and the median survival was 20.8 months (95 % CI, 16.5–26.3). The cumulative 2-year local-recurrence, regional-recurrence, and distant-metastasis rates were 52.2 % (95 % CI, 42.4–61.1 %), 12.8 % (95 % CI, 7.4–19.8 %), and 11 % (95 % CI, 6.0–17.6 %), respectively. 73 patients received concomitant cetuximab, and it was not significantly beneficial (HR = 1.34; 95 % CI, 0.80–2.26; p = 0.26). The cumulative incidences of grade ≥ 2 late toxicity was 42 % (CI95%: 33–51) at 24 months. Two grade 4 bleedings and no treatment-related deaths were reported. ConclusionIn a large retrospective series of SBRT reirradiation for recurrent or second primary H&N cancers, we observed a median OS of 20.8 months, with a cumulative incidence of grade ≥ 2 late toxicity of 42 % at 24 months. Such a treatment is feasible. However, local recurrence rates remain non-negligible, warranting further research. Radiosensitizer use is currently under study. Therefore, establishing a balance between therapeutic modifications and toxicity is essential.

Treatment patterns of targeted and nontargeted therapies and survival effects in patients with locally advanced head and neck cancer in Taiwan

BackgroundTaiwan’s National Health Insurance has covered targeted therapy, namely cetuximab, for locally advanced head and neck cancers (LAHNC) since July 2009. This study examines treatment trends and survival effects of locally advanced head and neck cancer patients before and after Taiwan’s National Health Insurance covered cetuximab.MethodsWe examined treatment trends and survival effects for patients with LAHNC using Taiwan’s National Health Insurance Research Database. Patients who received treatment within 6 months were categorized as either nontargeted or targeted therapy groups. We analyzed treatment trends with the Cochran-Armitage trend test and explored factors associated with treatment selection and survival effects using multivariable logistic regression and Cox proportional hazards models.ResultsOf the 20,900 LAHNC patients included in the study, 19,696 received nontargeted therapy, while 1,204 received targeted therapy. Older patients with more comorbid conditions, advanced stages and patients with hypopharynx and oropharynx cancers were more likely to receive targeted therapy with concomitant cetuximab treatment. Patients who received targeted therapy in addition to other treatment modalities had a greater risk of one-year and long-term all-cause mortality or cancer-specific mortality than those without receiving targeted therapy (P < 0.001).ConclusionsOur study found an increasing trend in cetuximab utilization among LAHNC after reimbursement in Taiwan, but overall usage rates were low. LAHNC patients receiving cetuximab with other treatments had higher mortality risk than those receiving cisplatin, suggesting cisplatin may be preferred. Further research is needed to identify subgroups that could benefit from concomitant cetuximab treatment.

Randomized phase 3 noninferiority trial of radiotherapy and cisplatin vs radiotherapy and cetuximab after docetaxel-cisplatin-fluorouracil induction chemotherapy in patients with locally advanced unresectable head and neck cancer

ObjectivesConcurrent chemoradiotherapy is the standard treatment for patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN); induction chemotherapy (ICT) may provide survival benefits in some patients. This study aimed to demonstrate the noninferiority of concomitant cetuximab plus radiotherapy (cet+RT) vs cisplatin plus radiotherapy (cis+RT) in patients with unresectable LA-SCCHN who were responsive to ICT. Materials and methodsThis randomized, open-label, phase 3 trial studied patients with unresectable LA-SCCHN who received 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil; TPF) followed by cis+RT (standard arm) or cet+RT (experimental arm). The primary endpoint was noninferiority of the experimental arm vs the standard arm in terms of overall survival (OS), based on a hazard ratio (HR) of < 1.3. Secondary endpoints included progression-free survival, overall response, safety, and quality of life (QOL). ResultsBetween July 15, 2008, and July 5, 2013, 519 patients were recruited and started ICT; 407 patients received post-ICT treatment (cis+RT, n = 205; cet+RT, n = 202). At a median follow-up of 43.9 (cis+RT) and 41.1 (cet+RT) months, median OS was 63.6 and 42.9 months with cis+RT and cet+RT, respectively (HR [90% CI] = 1.106 [0.888–1.378], P =.4492). There were no differences in progression-free survival, overall response rates, or adverse event rates between groups. There was greater late neurotoxicity with cis+RT than cet+RT (P =.0058). Several QOL dimensions improved with cet+RT vs cis+RT (physical functioning, P =.0287; appetite loss, P =.0248; social contact, P =.0153). ConclusionNoninferiority of cet+RT over cis+RT was not demonstrated.

Cetuximab and anemia prevention in head and neck cancer patients undergoing radiotherapy

BackgroundEpidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels intensifies RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, has been associated with lower rates of anemia for locally advanced head and neck squamous cell carcinoma (HNSCC). We hypothesized that concomitant cetuximab could prevent RT-induced anemia.MethodsWe queried our institutional head and neck cancers database for non-metastatic HNSCC cases that received RT with concomitant cetuximab or RT-only between 2006 and 2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. We only included patients who had at least one complete blood count in the 4 months preceding and after RT. We compared the prevalence of anemia (defined as hemoglobin (Hb) below 12 g/dL in females and 13 g/dL in males) and mean Hb levels at baseline and after RT. Improvement of anemia/Hb (resolution of baseline anemia and/or an increase of baseline Hb ≥1 g/dL after RT), and overall survival (OS) in relation to anemia/Hb dynamics were also compared.ResultsA total of 171 patients were identified equally distributed between cetuximab-plus-RT and RT-only groups. The cetuximab-plus-RT group had more locally-advanced stage, oropharyngeal and high grade tumors (p < 0.001 for all). Baseline anemia/Hb were similar, however anemia after RT conclusion was higher in the cetuximab-plus-RT vs RT-only (63.5% vs. 44.2%; p = 0.017), with a mean Hb of 11.98 g/dL vs. 12.9 g/dL; p = 0.003, for both respectively. This contributed to significantly worse anemia/Hb improvement for cetuximab-plus-RT (18.8% vs. 37.2%; p = 0.007). This effect was maintained after adjusting for other factors in multivariate analysis. The prevalence of iron, vitamin-B12 and folate deficiencies; and chronic kidney disease, was non-different. Baseline anemia was associated with worse OS (p = 0.0052) for the whole study cohort. Nevertheless, improvement of anemia/Hb was only marginally associated with better OS (p = 0.068).ConclusionsIn contrast to previous studies, cetuximab was not associated with lower rates of anemia after RT for nonmetastatic HNSCC patients compared to RT-alone. Dedicated prospective studies are needed to elucidate the effect of cetuximab on RT-induced anemia.

Does Cetuximab Reduce the Risk of Anemia in Patients Undergoing Radiation Therapy for Head and Neck Cancers?

<h3>Purpose/Objective(s)</h3> Epidermal growth factor receptor (EGFR) activation is associated with increased production of interleukin 6 (IL6), which is intensified by radiotherapy (RT) induced inflammatory response. Elevated IL6 levels promote RT-induced anemia by upregulating hepcidin causing functional iron deficiency. Cetuximab, an EGFR inhibitor, resulted in significantly lower rates of RT induced anemia for locally advanced head and neck squamous cell carcinoma (HNSCC) patients receiving definitive RT vs RT-alone according to Bonner et al; and other studies compared to concomitant chemotherapy. However, little is known for cases receiving cetuximab with RT in the adjuvant setting. <h3>Materials/Methods</h3> We queried our institutional HNSCC database for surgically staged non-metastatic cases that received adjuvant RT with or without concomitant cetuximab between 2006-2018. Cetuximab was administered for some high-risk cases medically unfit for platinum agents per multidisciplinary team evaluation. All included patients need to have at least one complete blood count pre- and post-RT end. We compared RT-cetuximab vs RT-alone for prevalence of baseline and post-RT anemia, defined as Hb below 12g/dL in females and 13g/dL in males, and mean hemoglobin (Hb) levels. We also assessed the improvement in Hb level post-RT (resolution of baseline anemia or Hb increase of at least 1g/dL above baseline), in addition to overall survival (OS) in relation to anemia/Hb dynamics. <h3>Results</h3> We were able to identify 66 patients who fit our inclusion criteria, of which 27 (41%) received RT-cetuximab, with the remaining receiving RT-alone (n=39, 59%). Median age was 62.5 years (range, 34-88 years), males 80%, black 29%, and 85% had a smoking history. The majority of cases (73%) were locally advanced. Oral cavity and oropharynx were the most common subsites (37.5% each), with HPV+ve cases representing 52% of the later. The study groups were well-balanced, except for higher rates of positive final surgical margins, and extracapsular space invasion and median RT dose (<i>p<0.05</i>). Baseline anemia was diagnosed in 70.4% in RT-cetuximab vs 76.9% in the RT-alone, p=0.76; with similar mean Hb level (11.7g/dL in both). Meanwhile, baseline iron, vitamin-B12 and folate deficiencies, and chronic kidney disease were non-different. After completion of RT, mean Hb was significantly higher in the RT-alone (12.9±1.4 g/dL) compared to RT-Cetuximab (11.9±2.1 g/dL), <i>p=0.02</i>. Nevertheless, higher anemia levels (70% vs 51%) and lower improvement of Hb post-RT (81.5% vs 92.3%) were both non-significant for RT-cetuximab vs RT-alone respectively, p>0.05 for both. On multivariate analysis, baseline anemia was associated with worse OS (p=0.0052), unlike improvement of Hb post-RT (p=0.14) with a corresponding better improvement of Hb (56.4% vs. 25.9%, p=0.014), albeit lower anemia levels (70% vs. 51%), was non significant (p=0.195). On multivariate analysis, lack of baseline anemia was associated with better OS (p=0.0052), whereas improvement of Hb post-RT was only marginal (p=0.068). <h3>Conclusion</h3> In a homogenous cohort of HNSCC patients treated postoperatively, concomitant cetuximab was not associated with lower RT-induced anemia, in contrast to previous studies.

Induction Chemotherapy Followed by either Chemoradiotherapy or Bioradiotherapy in Laryngeal Cancer.

Objective:In loco regionally advanced head and neck cancer, the superiority of concomitant cetuximab with radiation over radiation alone has been proven previously. But comparison between chemo radiation and bioradiation has not been well studied. Methods:Between October 2013 and August 2017, 38 patients with locoregionally advanced laryngeal cancer and more than 50% response to 3 cycles of induction chemotherapy (docetaxel and cisplatin: both with a dose of 75 mg/m2 on the first day and 5-flurouracil: 750 mg/m2 during days 1to 3; repeated every 21 days) were selected to receive either carboplatin (18 patients, AUC 1.5 , weekly) or cetuximab (20 patients, with loading dose of 400 mg/m2 and weekly dose of 250 mg/m2) with radiation. A Kaplan–Meier analysis was used to calculate progression free survival and overall survival rates. The log–rank test was used to compare overall survival between treatment groups. Results:The median follow up time was 36 months. The 2-year organ preservation rate of 78.9% was achieved. The 3- year progression-free survival rates of 65.2%, 72.7% and 58.2% were observed for all patients, carboplatin group and cetuximab group, respectively (p=0.4). The 3-year estimates of overall survival were 67.8%, 69.2 %, and 66.3 % for all patients, carboplatin group and cetuximab group, respectively (p=0.47). Concomitant carboplatin was discontinued in 3 patients due to toxicity Conclusion:Concomitant cetuximab is a reasonable alternative to concomitant chemotherapy. But the difference in treatment outcome between bioradiation and chemoradiation remains to be defined.

Cetuximab and Anemia Prevention in Head and Neck Cancer Patients Undergoing Radiotherapy

Introduction: Anemia is a major complication of treatment and a frequent cause of morbidity in cancer patients. Radiation therapy (RT) induces an inflammatory response and increased levels of interleukin-6 (IL-6), potentially causing anemia of chronic inflammation or worsening of pre-existing anemia. Head and neck cancers often overexpress epidermal growth factor receptors (EGFR), which can also lead to increased IL-6 levels. Cetuximab, an EGFR inhibitor, has been previously associated with a decreased incidence of anemia when added to cytotoxic chemotherapy (Vermorken et al,N Engl J Med, 2008). One study has also reported significantly lower rates of anemia in patients that received cetuximab with RT compared to those that received RT alone (Bonner et al,N Engl J Med, 2006). We hypothesized that cetuximab could prevent RT-induced anemia, possibly by decreasing IL-6 levels as a result of EGFR blockade. Methods: After obtaining IRB approval, we queried our institutional head and neck cancers database for nonmetastatic squamous cell carcinomas diagnosed between 2006 and 2018 that were treated with adjuvant or definitive RT with or without concomitant Cetuximab. Demographic data and tumor characteristics were collected, as well as pre and post RT laboratory values. We only included patients who had at least one complete blood count in the 3 months preceding treatment and another one up to 4 months after treatment. The primary outcome was the prevalence of anemia after RT. Secondary outcomes included mean hemoglobin levels and improvement of hemoglobin levels after RT conclusion. Anemia was defined as a hemoglobin level lower than 12g/dL in females and 13g/dL in males. Improvement of hemoglobin levels was defined as resolution of anemia after treatment in patients with anemia at baseline or an increase of at least 1g/dL in the rest of the included patients. Results: A total of 171 patients were identified, 85 in the cetuximab plus RT group and 86 in the RT-only group. Demographic characteristics were well-balanced among study groups, except for the Charlson comorbidity index, which was higher in the RT-only group (p=0.04). Most patients were treated in a definitive setting (61.4%), and the remainder received treatment in the adjuvant setting (38.6%). The cetuximab group had more patients with advanced disease (75.3% vs. 40.7%, p&amp;lt;0.001) and worse clinical and radiologic response rates to treatment. All-cause mortality was higher in the group of patients that received cetuximab (69.4% vs. 46.5%, p=0.004). The prevalence of anemia before treatment was similar, but there were lower rates of anemia in the RT-only group after treatment (63.5% vs. 44.2%, p=0.017), with a mean hemoglobin level of 11.98g/dL vs. 12.9g/dL for cetuximab combine with RT vs. RT alone (p=0.003). There was no difference in the levels prior to treatment (12.20g/dL vs 12.48g/dL, p =0.39). There was no difference in the percentage of patients that had improvement of hemoglobin levels between groups, although the majority achieved an improvement (69.4% vs. 80.2%, p=0.14). The prevalence of chronic kidney disease, vitamin B12 deficiency, folate deficiency, iron deficiency and iron overload was similar between groups. The overall survival was not statistically different for patients that had improvement in hemoglobin levels compared to those who did not. Conclusion: Cetuximab was not associated with lower rates of anemia after RT for nonmetastatic head and neck cancer patients compared to RT alone. It is possible that the heterogeneity of the research population due to the retrospective nature of this study contributed to our findings. Prospective studies are needed to better assess the effect of Cetuximab in anemia during RT. Figure Disclosures Siddiqui: Varian Medical Systems:Other: Instructor for Varian Clinical School and guest speaker- receive honorarium.

PH-0038: RT and concomitant CDDP vs cetuximab for head and neck cancer: long term outcomes of a randomized PH. II trial

PH-0038: RT and concomitant CDDP vs cetuximab for head and neck cancer: long term outcomes of a randomized PH. II trial

Does Age Impact Outcomes of Oropharyngeal squamous cell carcinoma?

It is well-established that human papilloma virus (HPV) positive (+ve) oropharyngeal (OP) squamous cell carcinoma (SCC) carries a better overall prognosis than HPV negative (-ve) tumors. We sought to investigate the impact of age upon survival endpoints for HPV +ve and -ve OP SCC as well as the differences in acute radiotherapy (RT) toxicity. We included all OP SCC cases treated definitively between 2010-2017. All cases underwent either surgery ± adjuvant RT; or definitive RT ± chemotherapy according to the multidisciplinary tumor board decision. After determining p16 status we dichotomized each HPV group by age at diagnosis into old (> or = 65 years) and young (<65 years) sub-groups. Patients' demographics, clinico-pathological data and treatment modalities were compared across age groups for both HPV sub-types. Log-rank test and Kaplan-Meier curves were utilized to measure effect of age on overall (OS), local recurrence free (LRFS) and distant metastases free (DMFS) survival for HPV +ve and -ve. For patients receiving RT we compared weight loss, feeding tube insertion, treatment breaks and hospitalization during RT as parameters for acute toxicity across age groups. We identified 217 OP SCC who fit our inclusion criteria. Seventy percent were HPV+ve, males were 82%, mean age at diagnosis was 61 years, 75% were white, 67% were ever smokers and 54% were frequent/heavy alcohol drinkers. According to AJCC 7th edition, Stages III and IVA formed 87%; however, these were regrouped as stage I (51%) and stage IVA (62%) as prevalent stages for HPV+ve and -ve respectively as per AJCC 8th version. Definitive CRT was utilized in 58% and surgery ± adjuvant therapy in 31% of the study cohort. For HPV+ve sub-group, 31% were old (n=47); whereas they constituted 40% (n=27) of HPV-ve cases. Clinicopathological and treatment characteristics were generally equivalent among age groups except that HPV +ve younger patients had more adequate surgical margins (≥5mm) (78% vs 36%; p=0.03) than old; and HPV-ve old cases had a trend towards more utilization of concomitant cetuximab (30% vs 13%; p=0.09) than younger ones. All endpoints were not significantly different between old vs young HPV+ve cases with 2-year OS and LRFS of (64% vs 59%; p=0.41 and 88% vs 87%; p=0.98 for both respectively). Similar outcomes were observed between study age groups for HPV-ve cases (p>0.05 for all endpoints). Hospitalization during RT was more frequent in old patients (44% vs 28%; p=0.03). Median weight loss during RT was 9.5% (0-22%) vs 9.3% (0-17%) for old vs young (p=0.35) and RT breaks were also non-significant (39% vs 27%, p=0.8). Feeding tubes were inserted after RT initiation in 41% of old and 36% in young (p=0.5). Older patients with OP SCC have equivalent outcomes compared to younger ones irrespective of HPV status. Optimal treatments must be offered following standard of care as determined by a multi-disciplinary group of providers.

The predictive and prognostic value of low skeletal muscle mass for dose-limiting toxicity and survival in head and neck cancer patients receiving concomitant cetuximab and radiotherapy

PurposeThis study aims to investigate the predictive value of low skeletal muscle mass (SMM) for cetuximab dose-limiting toxicity (DLT) and its prognostic value in head and neck squamous cell carcinoma (HNSCC) patients treated with concomitant cetuximab and radiotherapy.MethodsPatients diagnosed with HNSCC and treated with primary or adjuvant concomitant cetuximab and radiotherapy were included. Clinical and demographic variables were retrospectively retrieved and SMM was measured at the level of the third cervical vertebra using pre-treatment diagnostic computed tomography or magnetic resonance imaging. An optimal cut-off value for low SMM was determined based on the lowest log-likelihood associated with cetuximab DLT. A multivariate linear regression model was used to determine predictive factors for cetuximab DLT. The prognostic value of low SMM for disease-free and overall survival was analyzed using Kaplan–Meier curves.ResultsThe optimal cut-off value for low SMM as a predictor of cetuximab DLT was an LSMI ≤ 45.2 cm2/m2. Of the 91 included patients, 74.7% had low SMM and 30.8% experienced cetuximab DLT. At multivariate analysis, low SMM had no predictive value for DLT (OR 0.83; 95% CI 0.27–2.56; p = 0.74). The Kaplan–Meier curve demonstrated that patients with low SMM had significantly lower overall survival (Log Rank χ2 = 5.87; p = 0.02).ConclusionLow SMM is highly prevalent in HNSCC patients treated with concomitant cetuximab and radiotherapy. Low SMM has no predictive value for cetuximab DLT in HNSCC patients. Low SMM is probably not a prognostic factor for overall survival in highly selected HNSCC patients treated with concomitant cetuximab and radiotherapy and unfit for platin-based chemotherapy.

Preoperative chemotherapy and radiotherapy concomitant to cetuximab in resectable stage IIIB NSCLC: a multicentre phase 2 trial (SAKK 16/08)

BackgroundNeoadjuvant chemotherapy (CT) followed by radiotherapy (RT) and surgery showed a median survival of 28.7 months in resectable stage IIIB non-small-cell lung cancer (NSCLC) patients (pts). Here, we evaluate the impact of concomitant cetuximab to the same neoadjuvant chemo-radiotherapy (CRT) in selected patients (pts) with NSCLC, stage IIIB.MethodsResectable stage IIIB NSCLC received three cycles of CT (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3w) followed by RT (44 Gy in 22 fractions) with concomitant cetuximab (250 mg/m2, q1w) and subsequent surgery. The primary endpoint was 1-year progression-free survival (PFS).ResultsSixty-nine pts were included in the trial. Fifty-seven (83%) pts underwent surgery, with complete resection (R0) in 42 (74%) and postoperative 30 day mortality of 3.5%. Responses were: 57% after CT-cetuximab and 64% after CRT-cetuximab. One-year PFS was 50%. Median PFS was 12.0 months (95% CI: 9.0–15.6), median OS was 21.3 months, with a 2- and 3-yr survival of 41% and 30%, respectively.ConclusionsThis is one of the largest prospective phase 2 trial to investigate the role of induction CRT and surgery in resectable stage IIIB disease, and the first adding cetuximab to the neoadjuvant strategy. This trial treatment is feasible with promising response and OS rates, supporting an aggressive approach in selected pts.

PO-060 Outcomes from concomitant cetuximab with radiotherapy in HNSCC: A retrospective cohort study

PO-060 Outcomes from concomitant cetuximab with radiotherapy in HNSCC: A retrospective cohort study

Correction to: A Phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

Errors were subsequently identified in the article and the following corrections should be noted.

Multicenter Randomized Double-Blind, Placebo-Controlled Trial GORTEC (Groupe Oncologie Radiotherapie Tete et Cou) 2009-01 Evaluating the Effect of the Regenerating Agent on Radiodermatitis of Head and Neck Cancer Patients

Concomitant cetuximab and radiation therapy (RT) can induce severe radiodermatitis in patients with head and neck cancer (HNC). OTD70DERM, a regenerating agent (RGTA), is a structural and functional analogue of glycosaminoglycans. Preclinical studies have shown that topical RGTA can markedly reduce radiation-induced mucosal and cutaneous toxicities without tumor protection. The present study aimed to evaluate the effect of topical RGTA on radiodermatitis in patients with HNCundergoing RT and cetuximab, for whom RT-induced skin reactions are frequent and/or severe. The primary endpoint was the incidence of grade ≥2 radiodermatitis. We performed a multicenter, randomized, double-blind, placebo-controlled trial of patients with newly diagnosed HNC undergoing conventionally fractionated RT (70Gy in 35 fractions) and weekly cetuximab. Patients were randomized 1:1 to receive topical OTD70DERM or placebo on irradiated skin once daily. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to evaluate radiodermatitis (photographs of radiation zone). The Dermatology Life Quality Index score was also evaluated. All the skin reactions seen on the photographs were scored independently by 2 outside experts. Of the 76 randomized patients (38 in each arm), 72 were available for the final radiodermatitis evaluation (37 in the RGTA arm and 35 in the placebo arm). No significant difference was observed concerning the incidence or duration of grade ≥2 radiodermatitis between the 2 arms (81% for RGTA vs 80% for placebo; P=.9). Also, no significant difference was found between the 2 arms regarding grade ≥2 radiodermatitis evaluated by the 2 experts using the photographs of 68 patients (76% vs 74%; P=.78). Finally, no significant difference was found in the Dermatology Life Quality Index score (score >10, 15% vs 20%; P=.45). Despite the good preclinical rationale, RGTA did not reduce the incidence and severity of radiodermatitis in patients with HNC.

Cetuximab or nimotuzumab plus intensity-modulated radiotherapy versus cisplatin plus intensity-modulated radiotherapy for stage II-IVb nasopharyngeal carcinoma.

To compare intensity-modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II-IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with stage II-IVb NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4). Efficacy and safety were compared between the CTX/NTZ and CDDP groups of this well-balanced cohort. Furthermore, we conducted multivariate analysis and subgroup analysis based on all the 1,837 eligible cases. There was no significant difference between CTX/NTZ group and CDDP group in terms of DFS (3-year, 86.7% vs. 86.2%, p > 0.05), LRRFS (96.2% vs. 96.3%, p > 0.05), DMFS (91.1% vs. 92.3%, p > 0.05) and OS (91.7% vs. 91.9%, p > 0.05). Subgroup analysis demonstrated a significant interaction effect between patients with IMRT plus CTX/NTZ and N3 node stage on LRRFS with the highest risk of loco-regional relapse (HR 8.85, p = 0.001). Significantly increased hematologic toxicities, gastrointestinal reactions were observed in the CDDP group (p < 0.05). Patients of 3.4-4.7% experienced severe hematologic toxicities during the treatment with concomitant CTX and NTZ. Increased rate of CTX related-skin reaction and mucositis was observed in the CTX group. CTX/NTZ used concurrently with IMRT may be comparable to those of the standard CDDP-IMRT combination for maximizing survival for patients with stage II-IVb NPC.

Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab.

Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity. We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck. Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%). Sixty-nine patients received at least 7cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade≥3 dermatitis; grade≥2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade≥3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56days (47-75) compared to 51days (47-65) in patients who did not require toxicity-related radiation interruptions (p<0.05). After a median follow-up of 17.5months (1.3-107.6) for all patients, median overall survival was 17.9months (95% CI: 12.7-23.2), and loco-regional control (LRC) was 9.2months (95% CI: 3.9-14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade≥2 were independent prognostic factors for LRC (p=0.023 and p=0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p=0.048 and 0.052, respectively). Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.

Retrospective evaluation of concomitant cetuximab and radiotherapy tolerance for locoregional advanced head and neck squamous cell carcinoma treatment in patients unfit for platinum-based chemotherapy.

Radiotherapy associated with cetuximab (Cet-RT) is an alternative treatment to platinum-based chemoradiotherapy in locally advanced head and neck carcinoma (LAHNC). Reviews suggest that the use of cetuximab is associated with poorer tolerance in patients unfit for chemotherapy than in pivotal trial. We retrospectively studied patients first treated by Cet-RT for LAHNC presenting contraindications to chemoradiotherapy. Objectives were treated population description, acute tolerance, progression-free survival (PFS), overall survival (OS), and 3-month clinical response. Eighty-eight patients were included. Treatment was completed without delay for 43 patients. Grade 3-4 acute toxicity was described in 44.3%: mucositis (n = 20), radiodermatitis (n = 25) folliculitis (n = 10), and anaphylaxis (n = 6). Fourteen patients died during treatment. Median PFS and OS were 6.3 and 18.7 months, respectively. We confirm that Cet-RT tolerance in unfit patients is poorer than that in trials. Survival data illustrate patients' frailty and suggest that balanced use of Cet-RT is required in this population.

Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer

We report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer. The data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites. The endpoints of interest were locoregionalcontrol (LC), metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). Severe and fatal infectious complications were also reanalyzed to more thoroughly investigate the association between CTX treatment and potentially life-threatening reactions. A total of 33 patients had OPC. The HPV status was available for 30 of the 33 patients. Thus, 3 patients treated with CDDP but with unknown HPV status were excluded from the survival analysis. The small number of patients in each group did not allow for significance to be reached for any of the outcomes analyzed. A trend favored the CDDP arm in the p16-positive group for the 2-year LC and OS/CSS rates (100% vs 72.9% and 100% vs 77.8% for CDDP vs CTX). In this group of patients, the hazard ratio for the treatment arm (CTX vs CDDP) was 4.7 (95% confidence interval [CI] 0.5-40.3) for LC, 3.4 (95% CI 0.4-30.5) for OS, and 2.4 for CSS (95% CI 0.2-23.2). A survival benefit favoring the CDDP arm was not evident in the p16-negative OPC group or for patients with cancer located in other sites. Serious or fatal infectious complications occurred only in the CTX arm. In patients with p16-positive OPC in the CTXMAB+RT trial, CTX had lower efficacy than CDDP, with possible implications for treatment selection in this clinical setting.

Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas.

Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed.

G14 - Intensity-modulated radiotherapy and cetuximab for frail patients with loco-regionally advanced head and neck cancer

Background: The combination of radiotherapy (RT) and concomitant cetuximab demonstrated to be superior to RT alone in loco-regionally advanced squamous cell head and neck cancer (SCHNC). The benefit in terms of response rate, progressions-free survival (PFS) and overall survival (OS) has been obtained without increased toxicity. The objective of this study was to evaluate the clinical impact of such approach in frail patients. Methods: From january 2010 to december 2014 15 patients affected by stage III-IV SCHNC (oral cavity, oropharynx, and hypopharynx) not candidate to surgery or chemoradiation according to severe comorbidities or age (> 80 years) were treated with a combination of Intensity-Modulated RT (IMRT) and cetuximab with curative intent. Cetuximab was administered starting one week before IMRT at a loading dose of 400 mg/m2 i.v. followed by 250 mg/m2 i.v. weekly for a total of 8 infusions. Results: In this series the male/female ratio was 1.5 and the median age was 79 years. All patients but one completed IMRT along with 8 cycles of concomitant cetuximab whose median dose intensity was 95%. A complete response was achieved in 11 of 15 patients (73.3%). Three patients had residual nodal disease and underwent salvage neck dissection. Seven patients (46.7%) had loco-regional relapse and five of them developed distant metastases. With a median follow up of 58 months, the duration of locoregional control was 21 months (range, 1-59), median PFS was 16 months and median OS 34 months. Four patients (26.7%) were still alive at five years. Grade 3/4 adverse events occurred in 53.3% of cases, mostly oral mucositis and skin rash. With a careful pre-medication consisting of anti-histamine and steroidal drugs no infusional reactions were documented. One toxic death was registered in a 85-year old woman who died during IMRT as a consequence of severe sepsis. Conclusions: Cetuximab plus definitive IMRT is a feasible and effective treatment for loco-regionally advanced SCHNC. Even in frail patients it can provide good clinical outcomes along with an accettable toxicity profile. This combination allows a chance of cure for a subset of patients not suitable for chemotherapy or major surgery. The results in terms of PFS and OS are clearly inferior if compared to a standard patient population, nonetheless adding cetuximab to IMRT offer some chance of long survivorship to patients in poor clinical conditions, without dramatically altering their quality of life.