Weeks In Arm Research Articles

Effect of acute kidney injury and overall survival in patients with postoperative head and neck cancer who received chemoradiotherapy with cisplatin: A supplementary analysis of the phase II/III trial of JCOG1008.

In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m2) was non-inferior to 3-weekly cisplatin (100 mg/m2) for postoperative high-risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose-limiting toxicity effect of cisplatin, affects overall survival (OS). We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5-fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log-rank test. The total incidence of AKI was lower in the weekly arm than in the 3-weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3-weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m2 vs. 239.2 mg/m2; p = 0.94), but lower in the 3-weekly arm for those who developed AKI (median, 276.3 mg/m2 vs. 297.4 mg/m2; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3-weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21). In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3-weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m2 in this setting.

Efficacy and Safety of Concizumab Prophylaxis in Patients with Hemophilia A or B without Inhibitors: 56-Week Cut-Off Results of the Phase 3 explorer8 Study

Introduction Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody in development as a once-daily subcutaneous prophylactic treatment for hemophilia of all subtypes. Results from the 56-week cut-off of the prospective, multicenter, open-label explorer8 study (NCT04082429; phase 3) in patients with hemophilia A or B without inhibitors (HA/HB) are presented, further to the 32-week confirmatory analysis cut-off (CACO) results previously reported (Chowdary P et al. ISTH 2023, OC 59.1). Aim To assess the longer-term efficacy and safety of daily concizumab prophylaxis in patients with HA/HB. Methods Male patients (aged ≥12 years) with HA/HB were randomized 1:2 to no prophylaxis (arm 1; 24 weeks) or concizumab prophylaxis (arm 2; ≥32 weeks) or assigned to non-randomized concizumab prophylaxis (arms 3 and 4; ≥32 weeks). After the main part of the trial (24 weeks for arm 1), patients in arm 1 could switch to concizumab prophylaxis. After treatment restart following the treatment pause due to thromboembolic events, patients received a 1.0 mg/kg concizumab loading dose on Day 1, followed by an initial 0.20 mg/kg daily dose starting on Day 2, with potential adjustment to 0.15 or 0.25 mg/kg based on measured plasma concizumab concentration after week 4. Assessments at the 56-week cut-off included efficacy, safety, pharmacokinetic and pharmacodynamic measurements. Informed consent/ethics committee approval were obtained. Results The study included 148 patients (HA, n=82; HB, n=66), of which 21 patients were randomized to no prophylaxis (arm 1: HA, n=9; HB, n=12), 42 patients to concizumab prophylaxis (arm 2: HA, n=18; HB, n=24) and the remaining 85 patients were assigned to concizumab prophylaxis (non-randomized arms 3 and 4). After the main part of the trial, 17 patients from arm 1 switched to concizumab prophylaxis, receiving the same dosing regimen as patients in arms 2‒4 when first starting on concizumab. A total of 132 patients (HA, n=73; HB, n=59) completed the 56-week cut-off. The overall median (interquartile range) annualized bleeding rate (ABR) on concizumab prophylaxis in arms 1‒4 was 1.7 (0.0‒4.5) for HA and 2.8 (0.0‒6.4) for HB (Table 1); these results were also supported by the supportive secondary efficacy assessments. After treatment restart, no thromboembolic events were reported (Table 2). A total of 30 serious adverse events (AEs) were reported in 20 patients at the 56-week cut-off. As previously reported at CACO, one patient experienced a serious AE with fatal outcome (intra-abdominal hemorrhage) and 6 patients experienced AEs leading to withdrawal of concizumab treatment. The rate of injection site reactions was comparable to CACO. No hypersensitivity type reactions were reported in the study and low-titer anti-concizumab antibodies were detected in a total of 21 patients at the 56-week cut-off, with no apparent impact on bleeds or AEs. Concizumab plasma concentration remained stable over time. Free TFPI and thrombin peak levels continued to be stable over time. Conclusions Concizumab prophylaxis showed longer-term (≥1 year) efficacy in adult and adolescent patients with HA/HB at the 56-week cut-off, which was consistent with the results observed at CACO. Concizumab prophylaxis was considered safe and well tolerated in patients with HA/HB.

Impact of acute kidney injury on overall survival in postoperative patients with head and neck cancer who received chemoradiotherapy with cisplatin: A supplementary analysis of a phase II/III trial of JCOG1008.

6079 Background: A randomized phase II/III trial of JCOG1008 demonstrated that chemoradiotherapy (CRT) with weekly cisplatin at 40 mg/m2 (Weekly arm) was noninferior to 3-weekly cisplatin at 100 mg/m2 (3-weekly arm) in terms of overall survival (OS) for postoperative high-risk head and neck cancer (hazard ratio [HR], 0.69 [99.1% CI, 0.37 to 1.27 < 1.32]; J Clin Oncol 2022; 40: 1980-90). Acute kidney injury (AKI) is a major dose-limiting toxicity of cisplatin. Here, we investigated the impact of AKI on OS in patients treated with CRT in JCOG1008. Methods: A total of 251 patients who were treated with CRT in JCOG1008 were analyzed. AKI was defined as an increase in serum creatinine of ≥0.3 mg/dL or a 1.5-fold or more increase from baseline (≥stage I) within 30 days after completion of CRT, based on the AKI Network classification/staging system. OS in the two arms was compared by the development of AKI using the log-rank test. Results: The total incidence of AKI in the weekly arm was lower than that in the 3-weekly arm (38 of 122 [31.1%] vs. 56 of 129 [43.4%]). The incidence of stage II/III AKI was also lower in the weekly arm (8 of 122 [6.6%] vs. 19 of 129 [14.7%]). Total cisplatin dose was similar in patients who did and did not develop AKI in the weekly arm, but was lower in patients who developed AKI in the 3-weekly arm (Table). Moreover, no difference in OS was observed between patients who did and did not develop AKI in the weekly arm (HR, 1.06 [95% CI, 0.53 to 2.10]), whereas patients who developed AKI in the 3-weekly arm had poorer OS than those who did not (HR, 1.83 [95% CI, 1.04 to 3.21]). Conclusions: In this supplementary analysis of JCOG1008, development of AKI impacted OS in the 3-weekly arm, but not in the weekly arm. Consistent exposure to cisplatin through weekly fractionated administration appears of greater clinical significance than cumulative dose, providing maintenance of treatment intensity and better kidney safety, and likely also improving outcomes. Clinical trial information: jRCTs031180135 . [Table: see text]

A risk prediction model for cisplatin-induced acute kidney injury in patients with head and neck cancer who receive chemoradiotherapy: A supplement analysis of a phase II/III trial of JCOG1008.

12104 Background: Cisplatin-induced acute kidney injury (C-AKI) is a common reason for treatment interruption in head and neck cancer patients who receive chemoradiotherapy (CRT). We developed a risk prediction model for C-AKI in patients from a randomized phase II/III trial of JCOG1008, which demonstrated that CRT with weekly cisplatin at 40 mg/m2 (weekly arm) was noninferior to 3-weekly cisplatin at 100 mg/m2 (3-weekly arm) in terms of overall survival for postoperative high-risk head and neck cancer ( J Clin Oncol 2022; 40: 1980-90). Methods: Two hundred fifty-one patients received RT with a total of 66 Gy/33 fr concurrently with 3-weekly or weekly cisplatin. AKI was defined using the AKI Network classification/staging system as an increase in serum creatinine of ≥0.3 mg/dL or a 1.5-fold or greater increase from baseline (≥ stage I) by 30 days after the completion of CRT. AKI risk prediction models were developed by combining explanatory variables which were expected to contribute, including age, sex, ECOG performance status, primary site, pathological stage, diabetes mellites, hypertension, main nutritional method, treatment arm, serum albumin, serum magnesium, and creatinine clearance (CCr) at registration. A logistic regression model with the Akaike information criterion was used to explore the optimal model. Results: Ninety-four of 251 (37.5%) patients developed C-AKI in this study. The optimal C-AKI risk prediction model was composed of four factors, including a primary site (hypopharynx/larynx or oral cavity/oropharynx, odds ratio [OR] 1.92 [95% CI, 1.10 to 3.30]), treatment arm (3-weekly arm or weekly arm, OR 1.75 [95% CI, 1.02 to 3.00]), serum albumin (≤ 3.5 g/dL or > 3.5 g/dL, OR 2.06 [95% CI, 1.11 to 3.87]) and CCr ( < 90 mL/min or ≥ 90 mL/min, OR 1.85 [95% CI, 1.05 to 3.26]). The incidence of C-AKI increased in accordance with a total count of the four factors (Table): with a total count of 0-1, 2 and 3-4, the incidence of clinically relevant stage II/III C-AKI was 2.9%, 11.5%, and 22.6%, respectively. When total count was ≤1, the positive and negative predictive values for stage II/III C-AKI development were 16.1% and 97.0%, respectively. Conclusions: We developed a risk prediction model for C-AKI in head and neck cancer patients who receive CRT using primary site, cisplatin administration method, serum albumin, and CCr. The high negative predictive value of this prediction model may help rule out the development of moderate to severe C-AKI. Clinical trial information: jRCTs031180135 . [Table: see text]

Efficacy of Cryotherapy in Comparison to Standard Oral Care to Prevent Oral Mucositis during Concurrent Chemoradiotherapy in Head and Neck Cancer Patients

A quasi-experimental study was conducted at Radiation Oncology Department of National Institute of Cancer Research & Hospital (NICRH), Dhaka, Bangladesh, between November 2020 and October 2021, to determine the efficacy of cryotherapy in comparison to standard oral care to prevent oral mucositis in head and neck cancer patients during receiving CCRT. A total 100 Patients (50 patients in each arm) were included in this study according to inclusion and exclusion criteria by purposive sampling technique. All patients in Arm A and Arm B received total 66 Gray in 33 daily fractions, 1 fraction per day, 5 fractions per week and inj. Cisplatin 40mg/m² was given intravenously 2/3 hours before radiotherapy on 1st day and then weekly. Arm A received cryotherapy and Arm B received standard oral care. Intervention started from the 1st day of CCRT up to the end of CCRT. WHO oral mucositis grading and visual analogue scale (VAS) were employed to determine the effects. All the information was recorded in a pre-tested semi-structured questionnaire. Total 100 patients (50 patients in each arm) were enrolled. Mean age of the patients of Arm A and Arm B was 55.28±7.82 and 55.92±8.33 respectively. Male and female ratio was 6.14:1 in two Arms. Other demographic profile, baseline characteristics were statistically not significant in both arms (P>0.05). The grade-3 mucositis appeared after 5th week in Arm B and after 6th week in Arm A. The incidence of grade- 3 mucositis after 5th week during CCRT to 4 weeks after completion of therapy was 6% vs 0%, 14% vs 6%, 22% vs 10%, 14% vs 6%, 8% vs 2%, respectively for arm B and Arm A (P<0.05). Total number of patients suffering from grade 3 mucositis was 6 (12%) and 12 (24%) for Arm A and Arm B respectively (p value was <0.05). The mean duration of grade-3 or more mucositis between Arm A and Arm B was 2.04±1.78 and 10±1.72 days respectively (P<0.05). The difference of median pain intensity between two arms was not statistically significant for 1st and 2nd week (P>0.05). However, it was significant after 3rd week during CCRT to 4 weeks after completion of CCRT (P<0.05). Cryotherapy during CCRT may be beneficial to prevent oral mucositis and pain than maintaining standard oral care.
 CBMJ 2023 January: vol. 12 no. 01 P: 03-11

Three Weekly Versus Weekly Cisplatin: Comparison of two Different Chemotherapy Protocols with Concurrent Radiotherapy in Locally Advanced Head and Neck Cancer

Introduction: Chemoradiotherapy (CRT) with concurrent cisplatin-based chemotherapy is the treatment of choice of locally advanced head and neck cancers (LAHNC), but the optimal regimen of cisplatin remains contentious. Though 3-weekly cisplatin is the recommended schedule, it is associated with severe adverse reactions. A lower dose weekly schedule is generally accepted to be more tolerable and is widely used in our country. Methodology: Our study retrospectively compares the 3-weekly and the weekly concurrent cisplatin schedules in patients of LAHNC treated with CRT. Patients were selected for either schedule based on the treating physician’s preference. The two schedules were compared for treatment-related toxicities, radiotherapy interruptions, cumulative cisplatin doses delivered and overall survival (OS) as well as disease-free survival (DFS) at 2 years. Results: In our study, 43 patients received the 3-weekly schedule while 40 received the weekly schedule. Age, gender, disease stage or site did not affect selection for either regimen, except cancers of the nasopharynx and salivary glands, who almost exclusively received the 3-weekly schedule (90.1%). Patients who received adjuvant CRT after radical surgery were more likely to receive the weekly schedule (66.7%) while patients treated with up-front CRT were more often given the 3-weekly schedule (57.6%). Overall, the 3-weekly arm was associated with more toxicities and treatment breaks, but was more successful in delivering an adequate cumulative dose of cisplatin and had a better OS and DFS at 2 years follow up compared to the weekly arm. It also appeared that treating physicians were more likely to withhold one or more of the weekly cycles to manage treatment toxicity which lead to inadequate cumulative dosing in a high (45%) percentage of patients. Conclusion: Our study reiterates that the 3-weekly cisplatin arm has a better outcome profile than the weekly cisplatin arm at the price of increased toxicity. Weekly schedules have lower toxicities but may not achieve outcomes equivalent to 3-weekly unless adequate cumulative doses are achieved. As our study is retrospective and non-randomized, selection bias may have affected our results.

Alliance Foundation Trial 09: A Randomized, Multicenter, Phase 2 Trial Evaluating Two Sequences of Pembrolizumab and Standard Platinum-Based Chemotherapy in Patients With Metastatic NSCLC

IntroductionThe sequence of chemotherapy and pembrolizumab may affect antitumor immune response and efficacy of immunotherapy. MethodsThis multicenter, randomized, phase 2 trial was designed to evaluate the efficacy of two sequences of chemotherapy and pembrolizumab in patients with stage 4 NSCLC. Both arms were considered investigational, and the study used a “pick a winner” design. The primary end point was objective response rate by independent radiologic review after eight cycles (24 wk). Patients were randomized 1:1 to arm A (chemotherapy for four cycles followed by pembrolizumab for four cycles) or arm B (pembrolizumab for four cycles followed by chemotherapy for four cycles). Patients in both arms without disease progression after the initial eight cycles continued pembrolizumab until disease progression, unacceptable toxicity, or a maximum of 2 years. ResultsFrom March 2016 to July 2018, a total of 90 eligible patients were randomized (43 patients to arm A and 47 patients to arm B). The objective response rate at 24 weeks in arms A and B was 39.5 % (95 % confidence interval [CI]: 24.9%–54.1 %) and 40.4 % (95 % CI: 26.4%–54.5 %), respectively (p = 0.93). The progression-free survival in arms A and B was as follows: hazard ratio of B versus A equals to 1.06, 95 % CI: 0.68–1.66, p value equals to 0.84, and median progression-free survival of 5.8 months and 4 months, respectively. The overall survival was as follows: hazard ratio of B versus A equals to 1.04, 95 % CI: 0.63–1.74, p value equals to 0.85, and median overall survival of 15.5 months and 14 months, respectively. ConclusionsAdditional evaluation of either sequence in a phase 3 trial is not warranted.

Abstract 486: A phase Ib/II, open-label study evaluating the efficacy and safety of Toripalimab injection (JS001) or combination with Lenvatinib as a neoadjuvant therapy for patients with resectable hepatocellular carcinoma (HCC)

Abstract Background: There is no standard of care for neoadjuvant or adjuvant therapy for resectable hepatocellular carcinoma (HCC) yet. This trial is designed to explore the safety and efficacy of toripalimab or toripalimab in combination of lenvatinib as peri-operative treatment in HCC. (NCT03867370) Methods: In this ongoing phase Ib/II trial, patients (pts) with HCC who are eligible for surgical resection are enrolled. In neoadjuvant part of study, pts in Arm A are given toripalimab 480 mg iv single dose and pts in Arm B are treated with toripalimab 480mg iv plus concurrent lenvatinib 12 or 8 mg daily orally (based on body weight). All pts receive scheduled surgery on day 21-28. Lenvatinib is given until at least 7 days before surgery. Pts with R0 section confirmed by pathological analysis and MRI 4 weeks after surgery can take part in the adjuvant part of study. Toripalimab at 240 mg iv is given every 3 weeks for 48 weeks in Arm A. Pts in Arm B 1:1 randomized to receive toripalimab per same schedule as Arm A or toripalimab plus concurrent lenvatinib for 48 weeks. The primary objective is the pathological response. Secondary objectives include safety/tolerability, ORR, DCR, time to operation and PFS. Results: From 1 June 2019 to 7 Sep 2020, 18 pts were enrolled (10 in Arm A and 8 in Arm B) and 16 pts were evaluable. Two pts withdrew consent, one was due to the Covid-19 pandemic, and another received liver transplantation subsequently. The HCC in 11 pts were BCLC A stage, 4 pts were BCLC 0 and 1 pt BCLC B. 14 patients were in Chinese HCC staging CNLC Ia, 2 pts were in CNLC Ib. 81.3% patients were recurrent HCC. 16.7% (3/18) of patients experienced Grade 3+ AEs, 1 patient in Arm B experienced treatment-related SAE (hyperglycemia, well controlled). 16 pts (8 in Arm A and 8 in Arm B) proceeded with resection as planned. There were no delays or cancellations in surgery related to immunotherapy or target treatment. No visible tumor was observed in resected specimen in one patient. No pathological complete response (pCR) was observed in other 15 pts. 3 pts (20%) achieved major pathologic response (MPR, residual tumor in <50% tumor bed) and 2 in Arm A and 1 in Arm B. Multiple immunohistochemistry analysis of the immune infiltrates in the tumor microenvironment showed an increase in T-cell infiltration in MPR tumor tissue compared with non-response tumor tissue. Conclusion: PD-1 inhibition with toripalimab or toripalimab plus multikinase inhibition with lenvatinib result in promising antitumor activity as preoperative therapy in resectable HCC. There were no new or unexpected toxicities resulting from combination. Citation Format: Ying-Hong Shi, Yuan Ji, Wei-Ren Liu, Yan-Rui Pang, Zhen-Bin Ding, Xiu-Tao Fu, Xin Zhang, Cheng Huang, Yun-Fan Sun, Xiao-Dong Zhu, Hui-Chuan Sun, Jian Zhou, Jia Fan. A phase Ib/II, open-label study evaluating the efficacy and safety of Toripalimab injection (JS001) or combination with Lenvatinib as a neoadjuvant therapy for patients with resectable hepatocellular carcinoma (HCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 486.

Improved first trimester maternal iodine status with preconception supplementation: The Women First Trial.

Maternal iodine (I) status is critical in embryonic and foetal development. We examined the effect of preconception iodine supplementation on maternal iodine status and on birth outcomes. Non‐pregnant women in Guatemala, India and Pakistan (n ~ 100 per arm per site) were randomized ≥ 3 months prior to conception to one of three intervention arms: a multimicronutrient‐fortified lipid‐based nutrient supplement containing 250‐μg I per day started immediately after randomization (Arm 1), the same supplement started at ~12 weeks gestation (Arm 2) and no intervention supplement (Arm 3). Urinary I (μg/L) to creatinine (mg/dl) ratios (I/Cr) were determined at 12 weeks for Arm 1 versus Arm 2 (before supplement started) and 34 weeks for all arms. Generalized linear models were used to assess the relationship of I/Cr with arm and with newborn anthropometry. At 12 weeks gestation, adjusted mean I/Cr (μg/g) for all sites combined was significantly higher for Arm 1 versus Arm 2: (203 [95% CI: 189, 217] vs. 163 [95% CI: 152, 175], p < 0.0001). Overall adjusted prevalence of I/Cr < 150 μg/g was also lower in Arm 1 versus Arm 2: 32% (95% CI: 26%, 38%) versus 43% (95% CI: 37%, 49%) (p = 0.0052). At 34 weeks, adjusted mean I/Cr for Arm 1 (235, 95% CI: 220, 252) and Arm 2 (254, 95% CI: 238, 272) did not differ significantly but were significantly higher than Arm 3 (200, 95% CI: 184, 218) (p < 0.0001). Nominally significant positive associations were observed between I/Cr at 12 weeks and birth length and head circumference z‐scores (p = 0.028 and p = 0.005, respectively). These findings support the importance of first trimester iodine status and suggest need for preconception supplementation beyond salt iodization alone.

Randomized Controlled Study Comparing Efficacy and Toxicity of Weekly vs. 3-Weekly Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

Background: Head and Neck Cancer is a major public health problem in India, majority of which are lifestyle related, male predominant requiring dedicated infrastructure and human resource. The 5-year survival is 59% for all stages combined and only 45% in patients with locally advanced inoperable head and neck cancer using current chemoradiation schedules. Chemotherapy agents administered in the induction or concurrent setting comprise of taxanes (Docetaxel, paclitaxel), platinum compounds (Cisplatin, carboplatin) and fluorouracil (TPF). For patients with advanced Head and neck squamous cell carcinoma (HNSCC), 3-weekly TPF regimen is the established standard induction chemotherapy (ICT) option based on overall survival benefit. However, TPF regimen is known to be associated with significant dose limiting toxicities which may impair tolerance and effectiveness of therapy. In this study we assessed the efficacy and toxicity of weekly vs. 3-weekly Docetaxel, Cisplatin, and Fluoro-uracil (TPF) induction chemotherapy in locally advanced Head and neck squamous cell carcinoma (LA-HNSCC).Methods: This was an open labeled randomized two arm study with 41 patients in the 3-weekly TPF arm and 41 patients in the weekly arm. Patients were randomized using numbers from a randomization software, data recorded, and results were analyzed.Results: The weekly group achieved far greater symptom relief than 3-weekly group (72 vs. 64%). The overall response rates were similar in both arms (ORR 75.6 and 73.1% in the weekly and 3-weekly groups, respectively). Renal toxicity was significantly lower in the weekly group as compared to 3 weekly arm post three cycles of chemotherapy (CrCl 91.49 ml/min vs. 76.67 ml/min, respectively). The weekly group had predominantly grade I and II neutropenia (19.5 and 17.1%, respectively) as compared to 3-weekly group where grade III and IV neutropenia (31 and 12%, respectively) was more prominent (p-0.003). Among non-hematological toxicities, mucositis, nausea/vomiting, and diarrhea in the weekly group were significantly lower when compared to 3-weekly group. Progression free survival was slightly higher in the weekly group (18 months) when compared to 3-weekly group (15 months) which was not statistically significant.Conclusion: Weekly induction with TPF had lower toxicity and similar efficacy as compared to 3-weekly regimen in locally advanced HNSCC patients. Myelosuppression, which was the most serious and common complication of 3-weekly TPF regimens was notably low using the weekly regimen. Our results suggest that weekly TPF regimen may be a safer and effective alternative to 3-weekly TPF for treatment of LA-HNSCC. To our knowledge this is the first study reporting the efficacy of weekly TPF regimen in LA-HNSCC till date.

A comparative study of two schedules of concomitant Chemo-radiation with Cisplatin in locally advanced Head and Neck Cancer in Southern Rajasthan of India

Introduction: Head and neck cancer is the most common cancer in south-central Asia. It constitutes about 17.7% of all cancers occurring in India. Majority of them present with locoregionally advanced stage. Concurrent chemo-radiotherapy (CCRT) is recognized worldwide as a standard treatment option for locally advanced disease not amenable to surgical resection. Aims: To compare the differences in acute toxicities and response rate between two schedules (weekly and 3-weekly divided dose cisplatin-based) of concomitant chemo-radiation (CCRT) regimens in locally advanced head and neck squamous cell carcinoma (LHNSCC). Methods and Material: Total of 62 eligible patients of LHNSCC who satisfying the eligibility criteria were included in this study. After pre-treatment evaluation, patients were sequentially randomized into two arms: 31 patients were taken in each arm, Arm-A (weekly concurrent cisplatin group) and Arm- B (three weekly divided dose concurrent cisplatin groups). One patient in each arm dropped out due to poor compliance. In both the arms, radiotherapy was delivered to a dose of 66-70 Gy with a telecobalt machine as a conventional fractionation schedule. The primary endpoints of the study were to know the disease response and assessment of acute toxicity profile in both arms. Results: Among the in-field toxicity, we found mucositis as the commonest toxicity in both arms. Incidence of Grade-III (33.33% vs 40%) & Grade-IV mucositis (6.66% vs 10%), acute gastrointestinal toxicity (Nausea- 33.33% vs 46.33% & vomiting- 13.33% vs 20%), and acute renal toxicity (16.66% vs 10%) were found to be slightly higher in 3-weekly arm compared to weekly arm. Our study showed that higher the incidence of neutropenia grade-I (23.33% VS 16.66%) and acute skin reaction (40% vs 33.33%) occurred in the weekly CCRT arm compared to the 3-weekly CCRT arm. In view of treatment compliance and response rate, our study showed 3-weekly arm have a higher compliance rate of scheduled chemotherapy cycles and a higher response rate (CR=80% vs 70%) compared to the weekly arm. Conclusions: The present study concluded that the three weekly divided dose concurrent cisplatin arms having a slightly better response rate with a slight increase in mucosal toxicity while the weekly concurrent cisplatin arm having a reduced requirement of feeding tube placement, colony-stimulating factor and hospitalization for supportive care.

Compliance, toxicity and efficacy in weekly versus 3-weekly cisplatin concurrent chemoradiation in locally advanced head and neck cancer

AbstractAimWeekly low-dose cisplatin is routinely used in concurrent chemoradiation (CCRT) in locally advanced head and neck cancer (LAHNC), despite 3-weekly cisplatin being the standard of care. We compared compliance, toxicity and efficacy in weekly versus 3-weekly cisplatin CCRT in LAHNC.Materials and methodsIn this retrospective study, weekly cisplatin 50 mg flat dose was compared with 3-weekly cisplatin 100 mg/m2, when given in CCRT in LAHNC with curative intent. The study outcome was compliance, toxicity, loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS).ResultsEighty-four patients received CCRT from January 2013 to June 2017, 40 in weekly and 44 in 3-weekly arm. There was no difference between the arms not completing scheduled radiation therapy or chemotherapy. Patient receiving 200 mg/m2 cisplatin is higher in 3-weekly arm compared with weekly arm (75 versus 40·9%; p&lt;0·0015). Compared with 3-weekly arm, more patient in weekly arm developed grade ≥3 mucositis (52·5 versus 15·9%, p=0·0004), day care intravenous hydration (82·5 versus 38·6% &lt;0·0001) and in-patient admission (55·0 versus 18·2%; p=0·0004). The 2-year LRC, DFS and OS in weekly versus 3-weekly arm were: 70 versus 61·4% (p=0·406); 67·5 versus 56·8% (p=0·314); 67·5 versus 61·4% (p=0·558), respectively. The median time to LRR, DFs and OS was not reached.ConclusionsWeekly cisplatin is comparable with 3-weekly cisplatin in terms of compliance, disease control and survival, but with increased grade 3 mucositis and higher admissions for supportive care.

Abstract A69: Efficacy of alternative 28-day capecitabine dosing schedule in metastatic breast cancer

Abstract Background: The approved dosing schedule of capecitabine monotherapy in metastatic breast cancer (MBC) is 1250 mg/m2/dose administered days 1 through 14 of a 21-day cycle, but many patients (pts) have difficulty with this schedule due to side effects. Use of a lower starting dose such as 1000 mg/m2/dose or use of an alternative 28-day administration schedule (7 day on, 7 day off, repeat) allows for greater tolerability. Given limited data regarding efficacy of the alternative 28-day schedule, the primary objective of this study was to compare the efficacy of different schedules of capecitabine in patients with MBC. Methods: A retrospective chart review of pts with metastatic breast cancer who received capecitabine as monotherapy between 2002 and 2014 at the Ohio State University James Cancer Hospital was performed. We excluded any HER2-positive patients who had received concurrent HER2-targeted therapy. Pts who initiated therapy at a dose of 1000 mg/m2/dose were classified by these dosing schedules: Arm A (21 day), B (28 day), and C (changeover from 21 day to 28 day). Time to treatment failure (TTF) and overall survival (OS) were compared between dosing schedules using Kaplan Meier curves and log-rank tests. Results: A total of 181 MBC patients (Arm A: n = 113, Arm B: n = 25, Arm C: n = 43) with the following patient characteristics met eligibility criteria; 86.2% Caucasians, 13.8% non-Caucasians, 64.64% estrogen receptor (ER)-positive, 3.31% ER positive/HER2-positive, 2.22% ER negative/HER2-positive, and 29.83% triple-negative. The HER2-positive patients were excluded as they received concurrent therapy. A significant difference was seen in TTF (Arm A: 2.7 mo, Arm B: 2.8 mo, Arm C: 7.1 mo, p = 0.001) when comparing all dosing schedules as well as in OS (Arm A: 5.7 yrs, Arm B: 9.6 yrs, Arm C: 7.8 yrs, p = 0.006). After an initial dose reduction, patients on Arm B tolerated capecitabine for a longer period of time than patients on Arm A before needing a second dose reduction (Table 1). The median time on capecitabine for Arm A was 11.9 weeks and 12.6 weeks for Arm B, and the mean time of both Arm A and Arm B on capecitabine was 22.2 weeks. Patients with ER-positive breast cancer had improved TTF (4.45 months vs 2.32 months, p &amp;lt; 0.001) and OS (7.26 years vs 3.99 years, p &amp;lt; 0.001) compared to ER-negative breast cancer. Caucasians had improved TTF compared to African Americans (AA) and other races (3.90 mo vs 2.87 mo, p = 0.004); however, there was no significant difference in OS. Median starting dose (mg/m2): Arm A - 1000; Arm B - 1043; Arm C - 1000 Time to 1st dose reduction (weeks): Arm A - 6; Arm B - 6; Arm C - 6.5 Dose after 1st reduction (mg/m2): Arm A - 808; Arm B - 848.5; Arm C - 802 Time to 2nd dose reduction (weeks): Arm A - 6; Arm B - 20; Arm C - 8 Dose after 2nd reduction (mg/m2): Arm A - 599.5; Arm B - 690; Arm C - 697 Time to 3rd dose reduction (weeks): Arm A - 6; Arm B - 0; Arm C - 24 Dose after 3rd reduction (mg/m2): Arm A - 575; Arm B - 0; Arm C - 557 Table 1: Median dose (mg/m2) and median time to reductions (in weeks) Conclusions: Our study shows that patients who received the 28-day cycle initially or who were switched to the 28-day cycle appeared to have improved TTF and OS compared to patients on the 21-day cycle. It also shows that AA women had worse TTF on capecitabine when compared to Caucasians. One hypothesis for the improved TTF and OS is that this could be due to a higher total dose of capecitabine received in Arm B and C as shown in Table 1. We acknowledge that the limitations of our study include the sample size and the retrospective nature, and that further work needs to be done. However, the 28-day dosing schedule for capecitabine could be an alternative for elderly patients or patients with poor performance status who are at higher risk for drug toxicities. Citation Format: Nicole Olivia Williams, Anupama Suresh, Julie Stephens, Marilly Palettas, Michael J. Berger, Akaansha Ganju, Raquel Reinbolt, Robert Wesolowski, Anne M. Noonan, Jeffrey Bryan VanDeusen, Sagar Sardesai, Maryam Lustberg, Maryam B. Lustberg, Bhuvaneswari Ramaswamy. Efficacy of alternative 28-day capecitabine dosing schedule in metastatic breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A69.

Abstract P6-15-09: Final results of weekly (w) neoadjuvant carboplatin (Cp) added to paclitaxel (P) followed by epirubicin (E) and cyclophosphamide (C) in triple negative breast cancer (TNBC) patients (pts): A BSMO breast cancer task force phase II study

Abstract Introduction: Overall prognosis of early TNBC remains inferior to that of other breast cancer subtypes. Neoadjuvant platinum added to taxanes-anthracycline regimen has been reported to potentially improve pathologic complete response (pCR) and survival in TNBC pts. Aim: To report the final results of the efficacy and toxicity of the addition of weekly Cp to P and dose dense (dd) EC on the pCR rate in an open-label phase II study in stage II/III TNBC pts. Patients and methods: In the BSMO study sixty three pts received dd P (80mg/m2/wk) concurrent with Cp (AUC=2) for 12 weeks, added to bi-weekly E (90mg/m2) and C (600mg/m2) for 4 cycles, followed by surgery and radiotherapy. The primary endpoint was pCR in the breast and axilla. Additionally actual drug dosing and toxicities were registered. A correlative assessment of germline mutations in HRD genes is ongoing. Pts were monitored for clinical response by magnetic resonance and mammography, and also for relapse free survival and time to treatment failure. The study sample size has been calculated according to the optimal Simon's two-stage design method. The target sample size was 63 patients with 80% power to detect a pCR rate of &amp;gt; or=47% (α= 0.05). Results: Sixty three eligible pts with operable, non-inflammatory stage II/III TNBC were included. Most pts were between 40 and 59 yrs old and had clinical stage II disease. Forty percent were clinically node + and 68% were G3. Seventy three percent received breast conserving surgery. Sixty percent (38 out of 63 pts) achieved a pCR breast/axilla. Sixteen percent (10pts) missed three or more doses of wP, whereas at least 1 EC cycle was skipped in 19% (12pts). Sixty five percent had G3/4 neutropenia. Investigator reported febrile neutropenia occurred in 18 pts (28.5%) of which more than eighty percent during the EC part despite primary prophylaxis. Thrombocytopenia G3/4 was noticed in 10 pts (16%). Only four pts (6%) developed grade 3 peripheral neuropathy. Conclusion: The addition of weekly carboplatinum to neoadjuvant paclitaxel and ddEC is feasible and a pCR rate in the breast and axilla as high as 60% compares nicely with the results achieved with the similar 3 weekly carboplatinum arm of the CALBG 40603 trial. Febrile neutropenia rate was higher than the 3-weekly carboplatin arm in CALGB40603 trial, but occurred mainly during the EC part, while other toxicities are comparable. Future research could focus on this combination in the reverse sequence (first ECdd), which may lead to a better global haematological profile. Citation Format: Fontaine C, Cappoen N, Renard V, Van Den Bulck H, Vuylsteke P, Glorieux P, Dopchie C, Decoster L, De Grève J, Awada A, Wildiers H. Final results of weekly (w) neoadjuvant carboplatin (Cp) added to paclitaxel (P) followed by epirubicin (E) and cyclophosphamide (C) in triple negative breast cancer (TNBC) patients (pts): A BSMO breast cancer task force phase II study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-09.

Phase III randomized trial comparing weekly versus three-weekly (W3W) cisplatin in patients receiving chemoradiation for locally advanced head and neck cancer.

6007 Background: Chemoradiation (CRT) with cisplatin 100mg/m2 given 3-weekly is the standard of care in locally advanced head and neck squamous cell cancer (HNSCC). Substituting low dose weekly cisplatin has pharmacological rationale due to lower toxicity and enhanced radiosensitization but has never been compared to 3-weekly cisplatin. Methods: Phase III non-inferiority trial (CTRI/2012/10/003062) in patients with Stage III or IV (non-metastatic) HNSCC planned for radical CRT. Pts were stratified for T-category, N-category and intent of therapy (adjuvant versus definitive) and centrally randomized 1:1 to cisplatin 30mg/m2 weekly or 100mg/m2 3-weekly concurrently with radiotherapy. Primary endpoint was locoregional control (LRC); secondary endpoints included toxicity, compliance, response, progression-free survival and overall survival. The upper boundary of non-inferiority margin was set at 15%, assuming LRC of 60% with power 80% and alpha 0.05. Results: 300 pts were randomized,150 to each arm; median age 44 years (range: 25-67), males 89%; 71% were smokeless tobacco users. 61% were T4, 71% &gt; N2. 93% pts received CRT as adjuvant therapy for high-risk disease; indication was perinodal extension in 84%, close/ positive margins 8%. Median total treatment time was 86 days (IQR: 79-95). Median RT dose was 60 Gy (IQR 60-60 Gy) using shrinking field technique. In the weekly arm, 133 pts (88.7%) received &gt; 6 cycles; 14 (9%) required dose reduction, median cumulative cisplatin dose 210 mg/m2 (IQR 180-210). In the 3-weekly arm, 143 pts (95%) received &gt; 2 cycles, median cumulative cisplatin dose 300 mg/m2 (IQR 200-300); 12 (8%) required dose reduction. At a median follow up of 20 months (range: 1-49), locoregional relapses (LRR) occurred in 42.2% pts in the weekly arm and 29.6% pts in the 3-weekly arm, leading to an absolute difference in LRR of 12.7% (95%CI:1.89-23.41), p=0.035 by Gray’s test, HR-1.58 (95%CI:1.02-2.46). Acute &gt; grade 3 toxicity occurred in 85.3% pts in 3-weekly arm and 70.7% pts in weekly arm, p=0.002; 30.7% pts in the 3-weekly arm and 14% patients in the weekly arm required hospitalization for management of toxicity, p=0.001. Conclusions: 3-weekly cisplatin leads to 42% relative reduction in locoregional recurrence; it is superior to weekly cisplatin and should be the preferred regimen in CRT for HNSCC. Clinical trial information: CTRI/2012/10/003062.

Feasibility of utilizing a novel mhealth platform to deliver an evidence-based exercise intervention among testicular cancer survivors (TCS).

e21608 Background: Cardiovascular disease results in significant morbidity among TCS. Exercise for Cancer Patients (EXCAP) is a self-directed, individually tailored intervention that improves cardiovascular fitness in cancer patients, yet this has not been tested in TCS. We conducted a randomized phase II feasibility study of a novel exercise intervention using a mHealth delivery platform for EXCAP. Methods: We developed mHealth-EXCAP, which integrates data from a wearable digital activity tracker (DAT) into a patient’s electronic medical record (EMR), allowing providers to monitor and adjust EXCAP prescriptions via a patient-centered virtual portal. We randomized TCS ( &lt; 69 yr at diagnosis, any treatments, not in active or maintenance stage of exercise behavior) into 3 study arms: Arm 1 (mHealth-EXCAP), Arm 2 (EXCAP) and Arm 3 (usual care). TCS in both Arm 1 and 2 completed a 12 week EXCAP program with the goal of 12,000 daily steps and daily resistance exercises but Arm 1 used the mHealth platform. Arm 3 used a TCS care plan that promotes exercises. Results: 74 TCS were screened (32 ineligible; 23 declined), 19 consented and 14 (74%) completed study (3 withdrew; 2 lost to follow up) as of 1/31/17. Median age (yr) was 35 (Arm 1; n = 6), 48 (Arm 2; n = 4), and 48 (Arm 3; n = 4). In Arm 1, 83% TCS wore DAT and synced daily step data to EMR &gt; 90% of days. EXCAP prescriptions were adjusted via EMR portal on average 5 times over 12 weeks for each TCS and their weekly daily step goals were met 73% of the time. The number of daily steps recorded by DAT and those synced from DAT to EMR differed by a mean of 1.5% steps (±1.8). Median baseline number of daily steps were 5,525 (Arm 1), 6,795 (Arm 2), and 5,904 (Arm 3) and increased by 5,236, 1,160, and 1,544 respective steps at 12 weeks, with only Arm 1 (50% TCS) achieving &gt; 12,000 daily steps. At 3 months after intervention, 33% TCS in Arm 1 maintained &gt; 12,000 daily steps. On average, TCS in Arm 1 performed resistance exercises 26 minutes a day/5 times a week vs. 28 minutes a day/4 times a week in Arm 2. Conclusions: mHealth-EXCAP is feasible to implement among TCS and may decrease sedentary behavior. Ongoing research will examine its effects on cardiovascular fitness and risk factors.

Phase I study of nivolumab (nivo) + nab-paclitaxel (nab-P) ± gemcitabine (Gem) in solid tumors: Interim results from the pancreatic cancer (PC) cohorts.

412 Background: Immune checkpoint inhibitors, such as nivo, an anti−PD-1 antibody, have demonstrated antitumor activity in various cancers. Chemotherapy has demonstrated immune system activation via multiple mechanisms, providing a rationale for combination approaches. nab-P + Gem is a standard of care in PC which does not require immunosuppressive corticosteroids. Here we report interim results from 2 PC cohorts (Arms A and B) of a phase I study in patients (pts) receiving nivo + nab-P ± Gem for locally advanced or metastatic PC. Methods: This 2-part study was designed to identify dose-limiting toxicities (DLTs) of nivo + nab-P ± Gem in Part 1 and assess tolerability and efficacy in Part 2 dose expansion (+ Gem). Pts were DLT evaluable if they received ≥ 2 cycles of treatment and remained on study for 14 days after last dose or discontinued due to a DLT prior to completing 2 cycles. After Arm A, Part 1 was deemed safe, Arm B, Part 1 was initiated. In Arm A, pts with 1 prior chemotherapy regimen received nab-P 125 mg/m2 on days 1, 8, and 15 of a 28-day cycle (qw 3/4) + nivo 3 mg/kg on days 1 and 15 of a 28-day cycle starting with cycle 1. In Arm B, treatment-naive pts received the same regimen in Arm A + Gem 1000 mg/m2qw 3/4. Results: As of June 28, 2016, 11 and 6 pts were treated in Arms A and B in Part 1, respectively. No DLTs were reported in Arm A, and 1 in Arm B (nonimmune hepatitis, suspected to be due to Gem; resolved and pt continued nivo + nab-P without Gem). The most common grade 3/4 teatment-emergent AEs were pulmonary embolism, neutropenia, and anemia in 2/11 pts (18%) in Arm A and anemia in 2/6 pts (33%) in Arm B. Nine patients discontinued due to progressive disease (8 in Arm A, 1 in Arm B). Best overall response is shown in the Table. Median treatment duration was 12.6 and 15.5 weeks for Arms A and B, respectively. Clinical trial information: NCT02309177. Conclusions: These results indicate that adding nivo to nab-P ± Gem is feasible for pts with advanced PC, and antitumor activity of this regimen appears to be encouraging. Based on promising results from Part 1, Arm B, Part 2, is enrolling pts.[Table: see text]

Phase I/II Study of the Deacetylase Inhibitor Panobinostat As Maintenance Therapy after an Allogeneic Stem Cell Transplantation in Patients with High-Risk MDS or AML: The Panobest-Trial

Phase I/II Study of the Deacetylase Inhibitor Panobinostat As Maintenance Therapy after an Allogeneic Stem Cell Transplantation in Patients with High-Risk MDS or AML: The Panobest-Trial

508PD - 2Nd-Line Therapies After 1St-Line Therapy with Folfiri in Combination with Cetuximab or Bevacizumab in Patients with Kras Wild-Type Metastatic Colorectal Cancer (Mcrc)-Analysis of the Aio Krk 0306 (Fire 3)- Trial

ABSTRACT Aim: To investigated choice and duration of 2nd-line therapies according to 1st-line efficacy as well as overall survival (OS) according to 2nd-line therapy in FIRE-3: FOLFIRI plus either cetuximab (arm a) or bevacizumab (arm b) as 1st-line treatment of KRAS exon 2 wild-type mCRC. Methods: The study-protocol recommended 2nd-line therapy with FOLFOX plus bevacizumab in arm A and irinotecan plus cetuximab in arm B, but physician were free to choose any regimen. 2nd-line treatment was defined as any new anticancer drug for mCRC following 1st-line therapy. Duration of 2nd-line therapy was calculated as time from first to last application of 2nd-line treatment. Results: 260/297 patients in arm A and 250/295 patients in arm B were alive after 1st-line therapy. Of those, 78.5% of patients arm A and 76.4% in arm B received 2nd-line therapy so far. 1st-line PFS according to 2nd-line antibody use was 9.2 (anti-VEGF), comparing to 9.7 (anti-EGFR) and 11.3 months (no mAB); p = 0.001. Correspondingly, OS was 25.2 (anti-VEGF) vs. 23.7 (anti-EGFR) vs. 30.8 months (no mAB), p = 0.02. 1st-line PFS according to 2nd-line oxaliplatin (Ox) use was associated with 9.9 (Ox), comparing to 9.9 months (no Ox); p = 0.56. OS according to Ox-use was 27.1 (ox) vs. 29.1 months (no Ox); p = 0.10. 2nd-line therapy was administered for a median of 17.2 weeks in arm A and 14.0 weeks in arm b (p = 0.08). 2nd-line regimens with antibody-crossover were administered for a median of 23.9 weeks in arm A and 16.1 weeks arm B (p = 0.06). Updated results might be presented at the meeting. Conclusions: This post-hoc analysis indicates that 2nd-line application of mAbs was favoured in patients with shorter 1st-line PFS. Correspondingly, 2nd-line treatment without antibodies compared to antibody-based regimens was associated with longer OS. A trend towards longer 2nd-line therapy was observed in favour of patients receiving cetuximab as 1st-line therapy. Disclosure: S. Stintzing: Advisory boards: Roche/Genentech, BMS, Merck Honoraria: Roche/Genentech, Amgen, Merck, Sanofi Travel support: MerckSerono, Roche;L. Fischer von Weikersthal: Travel support: Roche;F. Kullmann: Honoraria: Roche;W. Scheithauer: Advisory boards and honoraria: MerckSerono, Roche; C. Giessen: Travel support: Roche;A. Jung: Advisory boards, and honoraria: MerckSerono;T. Kirchner: Advisory boards: Novartis, Amgen, Pfizer, Roche Honoraria: MerckSerono, Amgen, Roche, AstraZeneca research funding: MerckSerono, Amgen:V. Heinemann: Research grant: MerckSerono, Roche, Amgen Honoraria and advisory boards: MerckSerono, Roche, Amgen Travel support: MerckSerono. All other authors have declared no conflicts of interest.

O-0018 - 2ND-Line Therapies After 1st-Line Therapy with Folfiri in Combination with Cetuximab or Bevacizumab in Patients with KRAS Wild-Type Metastatic Colorectal Cancer (MCRC)-Analysis of the AIO KRK 0306 (FIRE 3)- Trial

ABSTRACT Aim: To investigated choice and duration of 2nd-line therapies according to 1st-line efficacy as well as overall survival (OS) according to 2nd-line therapy in FIRE-3: FOLFIRI plus either cetuximab (arm a) or bevacizumab (arm b) as 1st-line treatment of KRAS exon 2 wild-type mCRC. Methods: The study-protocol recommended 2nd-line therapy with FOLFOX plus bevacizumab in arm A and irinotecan plus cetuximab in arm B, but physician were free to choose any regimen. 2nd-line treatment was defined as any new anticancer drug for mCRC following 1st-line therapy. Duration of 2nd-line therapy was calculated as time from first to last application of 2nd-line treatment. Results: 260/297 patients in arm A and 250/295 patients in arm B were alive after 1st-line therapy. Of those, 78.5% of patients arm A and 76.4% in arm B received 2nd-line therapy so far. 1st-line PFS according to 2nd-line antibody use was 9.2 (anti-VEGF), comparing to 9.7 (anti-EGFR) and 11.3 months (no mAB); p = 0.001. Correspondingly, OS was 25.2 (anti-VEGF) vs. 23.7 (anti-EGFR) vs. 30.8 months (no mAB), p = 0.02. 1st-line PFS according to 2nd-line oxaliplatin (Ox) use was associated with 9.9 (Ox), comparing to 9.9 months (no Ox); p = 0.56. OS according to Ox-use was 27.1 (ox) vs. 29.1 months (no Ox); p = 0.10. 2nd-line therapy was administered for a median of 17.2 weeks in arm A and 14.0 weeks in arm b (p = 0.08). 2nd-line regimens with antibody-crossover were administered for a median of 23.9 weeks in arm A and 16.1 weeks arm B (p = 0.06). Updated results might be presented at the meeting. Conclusions: This post-hoc analysis indicates that 2nd-line application of mAbs was favoured in patients with shorter 1st-line PFS. Correspondingly, 2nd-line treatment without antibodies compared to antibody-based regimens was associated with longer OS. A trend towards longer 2nd-line therapy was observed in favour of patients receiving cetuximab as 1st-line therapy. Disclosure: S. Stintzing: Advisory boards: Roche/Genentech, BMS, Merck Honoraria: Roche/Genentech, Amgen, Merck, Sanofi Travel support: MerckSerono, Roche;L. Fischer von Weikersthal: Travel support: Roche;F. Kullmann: Honoraria: Roche;W. Scheithauer: Advisory boards and honoraria: MerckSerono, Roche; C. Giessen: Travel support: Roche;A. Jung: Advisory boards, and honoraria: MerckSerono;T. Kirchner: Advisory boards: Novartis, Amgen, Pfizer, Roche Honoraria: MerckSerono, Amgen, Roche, AstraZeneca research funding: MerckSerono, Amgen:V. Heinemann: Research grant: MerckSerono, Roche, Amgen Honoraria and advisory boards: MerckSerono, Roche, Amgen Travel support: MerckSerono. All other authors have declared no conflicts of interest.