A survey of medical oncologist’s opinions and perceptions regarding the management of dermatologic toxicities among mCRC patients treated with panitumumab in the United States.

639 Background: Dermatologic toxicity can be a limiting factor for the use of anti-EGFR therapy such as panitumumab. There is a paucity of real world data regarding the management of dermatologic toxicity among metastatic colorectal cancer (mCRC) patients treated with panitumumab in the United States (U.S.). The objective of this study is to describe oncologist's opinions regarding timing of skin rash management in relation to the initiation of treatment and perceptions regarding rash management strategies. Methods: A total of 125 oncologists were recruited from a national database via a third independent party. Eligible oncologists (i.e.: licensed and practicing oncologist who had treated at least three new or continuing mCRC patients with panitumumab in the last year) completed an online survey to report their opinions regarding the grade and type of dermatologic toxicities seen and their perceptions about management strategies for mCRC patients who are treated with panitumumab. The timing of rash management initiation was defined as pre-emptive (prior to the appearance of the rash) or reactive (after any signs of skin rash). Results: Based upon their collective experience, oncologists expect that 44% of patients will develop acneiform rash while on treatment. More than half (58%) of the oncologists reported they did not follow any practice guidelines regarding the management of dermatologic toxicities. The oncologists reported that they pre-emptively initiated the management of dermatologic toxicities in 53% of their patients. Skin moisturizer and sunscreen were reported to be the most critical preemptive management approach, while skin moisturizer, over-the-counter topical steroids, and oral antibiotics were reported to be the most critical reactive management tools for Grades 1, 2, and 3, respectively. Conclusions: Despite evidence from randomized controlled trials, a majority of oncologists do not follow guidelines for dermatologic management of EGFR-I rash. There is a clear need for better physician education and awareness of mitigation strategies for skin toxicity management in mCRC patients treated with panitumumab.

A standardized approach for managing chemotherapy-induced rash.

86 Background: Chemotherapy-induced rash can lead to disruptions or discontinuation of therapy, potentially leading to a poorer prognosis for patients. Methods: A retrospective chart review was performed at selected clinics to determine rash incidence, current rash management, and dose reductions, disruptions, and discontinuation of therapy due to rash for epidermal growth factor receptor-inhibitors (EGFR-I) during August and September 2013. A rash management algorithm containing preventative and treatment recommendations was created for selected EGFR-I (cetuximab, panitumumab, erlotinib) and implemented in the clinics’ electronic medical record as part of a pilot study from February through May 2014. When the EGFR-I were ordered, electronic alerts reminded providers of the algorithm. Pharmacists received electronic messages to ensure algorithm compliance. Nurses provided patients with a rash information sheet and preventative prescriptions. Providers assessed patients for rash during follow-up and instituted the rash treatment algorithm, if indicated. Through a chart review, rash incidence, and dose reductions, disruptions, and discontinuation of therapy due to rash were determined. Results: The retrospective chart review revealed 7 of 9 (78%) patients, in whom preventive medications were not utilized, developed rash with the selected EGFR-I. Treatment medications were required in 6 of 7 (86%) patients with rash. Even with treatment, 3 of 7 (43%) patients had a severe rash, making therapy modification necessary. A dose reduction was ordered for 1 patient, a disruption for another, and discontinuation of therapy for a third. During the pilot period, 6 of 7 (86%) patients developed rash, but none required dose reductions or discontinuation of therapy. Of the 6 patients who developed rash, 4 were adequately managed with preventive measures alone. Of the 2 patients who started rash treatment, 1 patient had rash resolution and the other patient continued treatment without any therapy modifications. Conclusions: An algorithm containing preventive and treatment recommendations for EGFR-I-induced rash may be more beneficial than reactive therapy alone in attenuation of dose reductions, disruptions, and discontinuation of therapy.

Treatment patterns and outcomes of acneiform skin eruptions from anti-epidermal growth factor receptor (EGFR) therapies for metastatic colorectal cancer (mCRC).

e19547 Background: Use of anti-EGFR therapies, such as cetuximab (Cmab) and panitumumab (Pmab), is associated with acneiform eruptions. Because research suggests a correlation between rash severity and outcomes in unselected patients, concerns remain that prophylactic treatment of rash may interfere with anti-tumor activities of these drugs. Our aims were to 1) characterize the treatment patterns for rash due to Cmab and Pmab and 2) evaluate if a prophylactic vs reactive approach to rash management modifies outcomes. Methods: All patients diagnosed with wild-type K-ras mCRC from July 2009 to June 2011 in British Columbia, Canada and prescribed either Cmab or Pmab were reviewed to describe patterns of prophylactic (before rash) and reactive (after rash) use of antibiotics and steroid creams. Using Cox regression, the relationship between rash management and overall survival was characterized. Results: In total, 119 patients were analyzed: median age at diagnosis was 63 years, 61% were men, 34% received Cmab and 66% Pmab, and median number of anti-EGFR treatment was 9 cycles. Rash occurred in over 90% of patients. Among them, reactive was favored over prophylactic treatment (66 vs 34%). Older patients (60+ years) and those with ECOG 0/1 were more likely to receive prophylactic creams (44 vs 20%, p=0.01) and antibiotics (62 vs 12%, p=0.01), respectively. There were no further differences in rash management based on other patient or tumor characteristics (all p>0.05). Median OS was 7.0 months. The number of treatment cycles and overall survival were similar in both prophylactic and reactive groups (both p>0.05). In Cox regression, ECOG 2+ correlated with worse survival than ECOG 0/1 (HR for death 5.25 95% CI 2.01- 9.23, p<0.01). However, survival outcomes were statistically similar between patients prescribed antibiotics prophylactically vs. reactively (HR=1.10, 95% CI 0.43-2.80, p=0.85) and between patients given steroid creams prophylactically vs. reactively (HR=2.00, 95% CI 0.58-6.92, p=0.27). Conclusions: Prophylactic treatment of anti-EGFR related rash is associated with similar outcomes as compared to reactive rash treatment in mCRC patients.

A phase I study of lapatinib (LPT) and cetuximab (CTX) in patients with CTX-sensitive solid tumors.

2590 Background: Preclinical research has shown that one mechanism of acquired resistance to CTX is via EGFR-ErbB2 heterodimerization, which can reactivate oncogenic pathways. LPT is a dual EGFR and ErbB2 intracellular tyrosine kinase inhibitor. A phase I translational clinical study was performed to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), and clinical activity of CTX and LPT in patients with EGFR-driven solid tumor malignancies that can be treated with CTX. Methods: Patients (Pts) were enrolled in a 3+3 dose escalation trial. Prior CTX therapy was allowed. CTX was given at 400mg/m2 on Cycle 1, Day 1 (C1D1), then 250 mg/m2 weekly. LPT dose levels (DL) were (1) 750mg, (2) 1000mg, and (3) 1250mg orally daily. Rash management included daily sunblock, steroid cream, and doxycycline. Cycle length was 21 days, and patients were assessed for toxicity through the end of C2, and for efficacy after every 2 cycles. Fresh tumor biopsies were obtained at baseline and at the end of C1 to compare EGFR and ErbB2 expression levels and EGFR related pathway activation. DNA from blood samples was analyzed for pharmacogenetic (PGx) variations and correlations with toxicity and pharmacokinetics (PK). Results: Between October, 2010 to January 2012, 13 pts were enrolled, with colon (4), lung (3), head and neck (3), and anal cancers (3); 10 were evaluable for toxicity. Treatment-related toxicities of any grade included: rash (67%), diarrhea (42%), fatigue (33%), nausea/vomiting (17%), and dehydration (8%). DLTs included G3 rash in 1 of 6 pts on DL1, and G3 diarrhea despite optimal therapy in 1 of 4 pts on DL2. Enrollment to DL2 continues. Of 7 pts evaluable for response, 1 had an uPR, 3 had SD, including 1 with SD of ≥4 cycles, and 3 had DP. Both patients with uPR and prolonged SD were treated on DL1. Tumor EGFR-ErbB2 and EGFR pathway phosphorylation analyses and PGx results will be presented. Conclusions: The combination of CTX and LPT is well tolerated with expected toxicities. Efficacy was seen even on DL 1. Phase II clinical studies in CTX-sensitive diseases such as colon and head and neck cancer are planned.

Treatment patterns and outcomes of acneiform eruptions from anti-epidermal growth factor receptor (EGFR) therapies for metastatic colorectal cancer (MCRC).

668 Background: Use of anti-EGFR therapies, such as cetuximab (cmab) and panitumumab (pmab), is associated with acneiform eruptions. Because prior research suggests a possible correlation between rash severity and outcomes in unselected patients, concerns remain that prophylactic treatment of rash may interfere with anti-tumor activities of these drugs. Our aims were to: 1) characterize the treatment patterns for rashes due to cmab and pmab; and 2) evaluate if a prophylactic vs. reactive approach to rash management modifies outcomes. Methods: All patients diagnosed with wild-type K-ras MCRC from July 2009 to June 2011 in British Columbia, Canada and prescribed either cmab or pmab were identified. We conducted a detailed retrospective review to describe prophylactic (before rash) and reactive (after rash) use of antibiotics and steroid creams. Using Cox regression, the relationship between rash management and overall survival was characterized. Results: In total, 78 eligible patients were analyzed: median age was 62 years, 65% were male, 27% received cmab and 73% pmab, and median number of anti-EGFR treatment was 9 cycles. Rash occurred in 88% of patients. Among them, reactive treatment was favored over prophylactic treatment (74% vs. 26%). There were no differences in rash management based on any patient or tumor characteristics (all p>0.05). Median overall survival was 7.2 months. The number of treatment cycles and overall survival were similar in both prophylactic and reactive groups. In Cox regression, ECOG 2+ correlated with worse overall survival (HR for death 5.95, 95% CI 1.68- 21.13). However, outcomes were statistically similar between patients prescribed antibiotics prophylactically vs. reactively (HR=1.47, 95% CI 0.37-5.90) and between patients given steroid creams prophylactically vs. reactively (HR=0.75, 95% CI 0.11-4.88). Conclusions: Prophylactic treatment of anti-EGFR related rash is associated with similar outcomes as reactive rash treatment in wild-type K-ras MCRC patients. Because rash can lead to decreased quality of life, pre-emptive skin treatment represents a reasonable strategy for patients on anti-EGFR therapies.