Dermatological toxicities of panitumumab in the treatment of patients with metastatic colorectal cancer (mCRC) from three clinical studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14551-14551 ◽  
Author(s):  
D. A. Drelich ◽  
L. Rose ◽  
M. Ramirez ◽  
M. Jacobs ◽  
E. Mitchell
Keyword(s):  
African American ◽  
Clinical Studies ◽  
Human Monoclonal Antibody ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Metastatic Potential ◽  
Median Number ◽  
Egfr Expression

14551 Introduction: Epidermal growth factor receptor (EGFr) expression in CRC is associated with metastatic potential and poor prognosis. Panitumumab, a fully human monoclonal antibody against EGFr, was approved for the treatment of patients with refractory mCRC. The main side effects of panitumumab include dermatological manifestations that have been termed “rash”. However, classification of the dermatological manifestations has not been clearly described. Methods: We summarized the dermatological manifestations of 19 patients from 3 clinical studies investigating the the safety and efficacy of panitumumab monotherapy in mCRC in a single institution. Two of these studies were open lable, phase 2 in design which enrolled patients with documented disease progression (PD) during or after adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin chemotherapy. In the other panitumumab was given in combination with irinotecan or oxaliplatin with bevacuzumab, 5FU, and leucovorin. Pts received panitumumab at 6mg/kg Q2W until PD or intolerability. Skin assessments were made q2w. Results: Five patients were men (26%) and 14 (73%) women; 12 were Caucasian (63%) and 7 (36%) African American. The median age was 53 (Range 38–80). Tumor response, disease control, and skin manifestations did not correlate with tumor EGFr levels as assessed by immunohisxtochemistry (Dako EGFR pharmDxtm). No enhancement of skin toxicity was observed when panitumumab was combined with chemotherapy. The median number of cycles received was 11 (Range 3–20). All pts experienced erythema; 17 macular/papular; 13 pustular; 18 acneiform rash; 15 pruritis; 3 honey crusting; 15 dry/flaking; 11 paronychia; 9 hirsuitism; 9 trichomegaly; and all 7 African American patients had significant hyperpigmentation. Photograph illustrations of each category and severity will be presented. Conclusion: Rash associated with panitumumab is common and can be classified according to the clinical dermatological manifestations; specific treatment strategies should be developed and evaluated accordingly. This is the first report of hirsuitism in women and hyperpigmentation in African Americans. [Table: see text]

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3146
Author(s):  
Patricia Fernández-Nogueira ◽  
Gemma Fuster ◽  
Álvaro Gutierrez-Uzquiza ◽  
Pere Gascón ◽  
Neus Carbó ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Cancer Associated Fibroblasts ◽  
Luminal A ◽  
Luminal B ◽  
Number Of Patients ◽  
Current Therapies

Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs’ role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.

A prospective pharmacogenomic (PG), pharmacodynamic (PD), and pharmacokinetic (PK) study of determinants of erlotinib toxicity

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3080-3080 ◽  
Author(s):  
C. M. Rudin ◽  
A. A. Desai ◽  
L. Janisch ◽  
M. Carducci ◽  
T. Karrison ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Positive Association ◽  
Skin Toxicity ◽  
Response Assessment ◽  
Blood Collection ◽  
Strong Correlations ◽  
Ca Repeat ◽  
Egfr Expression ◽  
Intron 1 ◽  
Skin Biopsies

3080 Background: A strong but unexplained association between skin toxicity (rash) and survival from erlotinib therapy has been noted for patients with several epithelial malignancies. The correlation between rash and clinical benefit appears to extend across classes of epidermal growth factor receptor (EGFR)-targeted agents. Several hypothetical explanations for this association have been suggested including polymorphisms of the EGFR locus as well as PD and PK variability. Methods: We conducted this 80-subject prospective study in patients with lung (N=43), head and neck (N=9), and ovarian cancer (N=28) given erlotinib 150 mg daily to evaluate several of these hypotheses. Patients underwent toxicity monitoring, response assessment, skin biopsies pretreatment and after 28 days for immunohistochemical (IHC) analysis, as well as blood collection for PK analysis and evaluation of EGFR genetic polymorphisms reported to influence EGFR expression level. Results: 72/80 subjects are evaluable for toxicity. Response correlates with both worst grade diarrhea (p=0.003) and rash (p=0.044). Initial PK analysis suggests a positive association between d15 erlotinib trough level and both diarrhea (p=0.091) and rash (p=0.076). Controlling for d15 erlotinib level, EGFR intron 1 CA repeat length is also associated with rash (p=0.030). Polymorphisms in the EGFR promoter (216 G/T and 191 C/A) correlated with diarrhea (p=0.053 and 0.005 respectively) but not rash. IHC analyses including EGFR, p-EGFR, Akt, p-Akt, ERK, and p-ERK have been completed on 35 paired, pre-post treatment skin biopsies and demonstrate no strong correlations with toxicity. Conclusions: These data suggest that both interindividual PK variability and EGFR polymorphisms may contribute to erlotinib toxicity. Erlotinib effects on EGFR signaling in skin do not appear to correlate with toxicity. Samples obtained in this study are available for analysis of other candidate PG determinants of both toxicity and PK variability. [Table: see text]

Epidermal growth factor receptor (EGFR) status in different stages of resected non-small cell lung cancer (NSCLC): Implications for treatment with EGFR-targeted monoclonal antibodies

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20015-20015
Author(s):  
R. Berardi ◽  
M. Scartozzi ◽  
M. Squadroni ◽  
A. Santinelli ◽  
A. Brunelli ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Background Level ◽  
Prognostic Indicator ◽  
Egfr Expression ◽  
Resected Nsclc ◽  
Advanced Stages ◽  
Epidermal Growth ◽  
Metastatic Neoplasm

20015 Background: Aim of our study was to verify potential changes in EGFR status in different stages of resected NSCLC. This was done in order to find out whether assessing the EGFR status could be considered an effective tool for planning therapy with EGFR-targeted monoclonal antibodies in different setting of patients. Methods: From January 1996 through December 2001, 439 patients underwent radical surgery for NSCLC at the Department of Thoracic Surgery of Università Politecnica delle Marche. EGFR expression was evaluated with an immunohistochemical technique on five micron-thick tissue sections obtained from specimens fixed in 10% (v/v) neutral buffered formalin and paraffin embedded.EGFR expression was detected as membranous and/or cytoplasmic brown staining of neoplastic cells with various intensity. Positivity for EGFR expression was defined as any membrane staining above background level. Both the primary and metastatic neoplasm were considered positive when ≥ 1% of the tumour cells had membranous staining. Results: Table 1 summarizes patients’ characteristics. Samples from 423 patients were available for EGFR analysis. EGFR immunohistochemical expression was found positive as follows: 15.8% in stage IIIB, 12.2% in IIIA, 2.3% in IIB, 5.3% in IIA, 4.8% in IB and 5% in IA. At multivariate analysis, EGFR status resulted indicator of prognosis both when considering all the patients and in the groups of patients with different stages of disease. Conclusions: Globally our findings seem to confirm the role of EGFR as a prognostic indicator in NSCLC. Furthermore the observation that EGFR is more frequently overexpressed in the advanced stages may suggest that EGFR-targeted treatment strategies could be more appropriated in this subgroup of patients. [Table: see text] No significant financial relationships to disclose.

Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: A phase II study of the Belgian Group of Digestive Oncology.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 245-245 ◽  
Author(s):  
I. Borbath ◽  
A. Ceratti ◽  
C. Verslype ◽  
A. Demols ◽  
T. Delaunoit ◽  
...  
Keyword(s):  
Skin Rash ◽  
Phase Ii ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Standard Of Care ◽  
Egfr Expression ◽  
Prior Systemic Therapy ◽  
Ecog Ps

245 Background: Cholangiocarcinomas (CCK) are uncommon tumors with an increasing incidence and a poor prognosis. Epidermal growth factor receptor (EGFR) expression and activation in CCK have been demonstrated. Methods: We conducted a multicenter phase II trial combining cetuximab (Ctx), an anti-EGFR chimerized IgG1 monoclonal antibody, to gemcitabine (Gem). Patients with either locally advanced (LA) or metastatic (M) CCK (excluding gallbladder) were included; no prior systemic therapy was allowed. Ctx was administrated at the initial dose of 400 mg/m2 and further injections at 250 mg/m2 every 7 days, and Gem was administrated at 1000 mg/m2 on days 1, 8, and 15 every 4 weeks. The primary endpoint was the progression-free survival (PFS) rate at 6 months. A Simon 2-stage design was used. We hypothesized that Gem/Ctx would improve 6 month-PFS rate from 20% to 40%. We needed 3 patients with PFS ≥ 6 months from the first 13 to further include a total of 43 patients. Results: Forty-four patients with advanced CCK (41% LA/59%M) were enrolled from 09/2008 to 01/2010. Median age was 61.5 years (range 40-86) and baseline ECOG PS was 0 for 68% and 1 for 32% of the patients. Forty-three percent of the patients had prior surgery. Forty-six percent of the patients were free from progression at 6 months. Median PFS was 5.8 months (95% CI, 4.4-7.4 m) and median overall survival was 11.6 months (95% CI, 8.7-14.6 m). Nine patients (20.9%) had partial response with a median duration of 5 months (range 2-10 m). Disease control rate (PR + SD > 8 weeks) was 81.4%. The most common grades 3/4 related-toxicities were haematological abnormalities (47.7%), skin rash (13.6%) and fatigue (11.3%). Due to toxicity, 6 patients discontinued study treatment; 14 and 3 patients had a Gem and Ctx dose reduction respectively. Among the nine responders, 8 experienced a skin rash of at least grade 2, suggesting a relationship between skin toxicity and efficacy. Conclusions: Our study met its endpoint, i.e., a PFS rate of 46% at 6 months, suggesting that Gem-Ctx combination had promising activity with a manageable toxicity profile in advanced CCK. Adding Ctx to the new standard of care Gem-cisplatin deserves further investigations in CCK. [Table: see text]

Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): A pooled analysis of five clinical trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4134-4134 ◽  
Author(s):  
J. Berlin ◽  
E. Van Cutsem ◽  
M. Peeters ◽  
J. R. Hecht ◽  
R. Ruiz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Phase Ii Studies ◽  
Common Skin

4134 Background: Panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFr), is approved for EGFr-expressing mCRC patients (pts) with disease progression (PD) on or following fluoropyrimidine (5FU)-, oxaliplatin (Ox)-, and irinotecan (Ir)-containing chemotherapy. Skin toxicities are common with panitumumab; we examined the association between severity of skin toxicity and panitumumab efficacy. Methods: Data from 5 clinical trials were pooled (4 phase II studies and 1 phase III study). Pts with mCRC had documented PD on or after 5FU, Ox, and/or Ir. Pts received panitumumab 6 mg/kg every two weeks (Q2W) or 2.5 mg/kg weekly (QW) until PD or intolerability. Tumors were assessed using modified WHO or RECIST criteria (blinded central review in 4/5 studies). Endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). PFS and OS were measured from enrollment. Only pts with =2 infusions (exposure over 2 wks for QW dosing or over 4 weeks for Q2W dosing) were analyzed to help correct for lead-time bias. Results: 612 of 640 pts were included in the analysis set (62% were male, 92% were white, and median age [range] was 61 [21, 88] years). The median (95% CI) duration of PFS was 8.4 weeks (8.0 to 11.3), the median (95% CI) survival was 6.9 months (6.2 to 7.9), and the ORR (95% CI) was 9.0% (6.8 to 11.5). The most common skin toxicities (any grade, grade 3/4) were erythema (54%, 4%) pruritus (53%, 2%), dermatitis acneiform (52%, 5%), and rash (39%, 2%). ORR, PFS, and OS appeared to favor pts with grade 2–4 skin toxicity vs pts with grade 0- 1 skin toxicity ( table ). Conclusion: In this large combined analysis, severity of skin rash was correlated with increased efficacy of panitumumab in terms of ORR, PFS, and OS. [Table: see text] No significant financial relationships to disclose.

Cetuximab in combination with docetaxel (T) in patients with operable, triple-negative breast cancer (TNBC): Preliminary results of a multicentre neoadjuvant pilot phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1057-1057
Author(s):  
Jean Marc Nabholtz ◽  
Marie-Ange Mouret-Reynier ◽  
Isabelle Van-Praagh ◽  
Véronique Servent ◽  
Jean-Philippe Jacquin ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Complete Response ◽  
Conservative Surgery ◽  
Median Number ◽  
Clinical Response Rate ◽  
Preliminary Results ◽  
Grade Ii ◽  
Grade Iii

1057 Background: Cetuximab is an antiboby targeting the epidermal growth factor receptor (EGFR) to which a role has been suggested in TNBC. Therefore, we evaluated the combination of docetaxel with cetuximab as neoadjuvant therapy of operable TNBC. Methods: 35 patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 6 cycles of T (100 mg/m2) q.3 weeks, in combination with weekly cetuximab (first dose : 400mg/m², then : 250 mg/m²/week) for 6 cycles. All patients underwent surgery at completion of ST. Complete pathologic response (pCR) was the primary endpoint (Sataloff : J Am Coll Surg 1995 ; Chevallier : Am J Clin Oncol 1993), with toxicity and biologic ancillary studies as secondary endpoints. Results: Patients characterisctics are as follows : mean age 48 [28-67] ; T1 : 3%, T2 : 73%, T3 : 24% (mean tumor size : 40 mm [15-100]) ; N0 : 61% and N1-N2 : 39%; invasive ductal carcinoma : 100%; Scarff-Bloom-Richardson Grade III : 73%, grade II : 27%. The median number of cycles was : T : 6 [1-6], cetuximab : 15 [1-18]. Pathological complete response was 24% according to Chevallier and Sataloff’s classifications and 28% if we consider response in breast. Preliminary results on 23 patients show an overall clinical response rate of 57% (22% CR). Conservative surgery was performed in 75% of cases. Skin toxicity was the main side-effect : grade II : 39%, grade III : 36%, grade IV : 3%. Neutropenia grade IV : 12.7%, febrile neutropenia : 1.3%, infection : 0%. Hand-foot syndrome grade III : 3%, grade II : 3%. Ungueal toxicity grade III : 3%, grade II : 33%. Conclusions: These preliminary results suggest that cetuximab in combination with Tappears to have a modest efficacy in operable TNBC. Clinical trial information: NCT00600249.

Safety of panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFr), in patients (pts) with metastatic colorectal cancer (mCRC) across clinical trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4138-4138 ◽  
Author(s):  
M. Peeters ◽  
E. Van Cutsem ◽  
J. Berlin ◽  
J. R. Hecht ◽  
R. Ruiz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Human Monoclonal Antibody ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Prior Therapy ◽  
Infusion Reactions ◽  
Epidermal Growth ◽  
Grade 3 ◽  
Age Range

4138 Background: Panitumumab is indicated in pts with EGFr-expressing mCRC refractory to chemotherapy. We present a summary of safety with panitumumab monotherapy in mCRC pts across 10 clinical trials. Methods: Data were pooled from pts enrolled in 10 clinical trials (including 2 extension studies). Pts received at least 1 dose of panitumumab at 2.5 mg/kg QW, 6 mg/kg Q2W, or 9 mg/kg Q3W. Adverse events were graded using NCI-CTC or CTCAE criteria. Results: A total of 920 mCRC pts were included in this analysis: 60% were male; 88% were white; median age (range) was 61 (20, 88) years. All pts had prior therapy; 77% had failed prior fluoropyrimidine, irinotecan, and/or oxaliplatin. Most (80%) pts received panitumumab 6 mg/kg Q2W; 17% and 3% of pts received panitumumab 2.5 mg/kg QW and 9 mg/kg Q3W, respectively. Median (range) follow-up time was 21 (1–124) weeks. A total of 7264 panitumumab infusions were administered with a median (range) of 5 (1–94) infusions/pt. Treatment-related adverse events (AE) were experienced by 94% (grade = 3, 20%) of pts. All pts had = 1 AE. The most common AEs were skin-related and GI toxicities ( table ). Skin-related AEs resulted in discontinuation in 2% of pts. Overall, 12% of pts discontinued panitumumab due to toxicity. Four (0.4%) pts had grade = 3 infusion reactions. In pts with postdose samples (n = 613), increased and persistent postdose levels of anti-panitumumab antibodies were detected in 0.5% of pts by ELISA and in 4.6% of pts by Biacore assay. Conclusions: Skin toxicity was common, but rarely treatment-limiting. Most AEs were mild to moderate and infrequently resulted in discontinuation. Infusion reactions and formation of anti-panitumumab antibodies were rare. The safety profile of 9 mg/kg Q3W panitumumab appeared consistent with other dosages; however, because of the small pt size further evaluation is needed. Panitumumab at 2.5 mg/kg QW and 6 mg/kg Q2W was well tolerated across 10 clinical studies. [Table: see text] No significant financial relationships to disclose.

Retrospective cohort study on the safety and efficacy of panitumumab for patients with metastatic colorectal cancer: The HGCSG1002 study—Analysis of adverse events.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 554-554
Author(s):  
Masayoshi Dazai ◽  
Hiraku Fukushima ◽  
Yasushi Sato ◽  
Satoshi Yuki ◽  
Hiroyuki Ohnuma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Human Monoclonal Antibody ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Line Treatment ◽  
Ecog Performance Status ◽  
Grade 3

554 Background: Panitumumab (Pmab) is a fully human monoclonal antibody specific to the epidermal growth factor receptor. It has been associated with very few infusion reactions, but has been pointed out more severe skin toxicity, compared to cetuximab which is a chimeric antibody.To evaluate the safety of Pmab for patients (pts) with metastatic colorectal cancer (mCRC) in daily clinical practice in Japan, retrospectively. Methods: Two hundred pts with mCRC treated by Pmab contained chemotherapy were retrospectively registered from 20 centers in Japan (HGCSG1002 study). Adverse events were evaluated using Common Terminology Criteria for Adverse Events(CTCAE) Version 4.0. Results: Of 195 pts were able to evaluate for adverse events. Patients’ characteristics were as follows; male/female 112/83, median age 64 (range 40-82), ECOG performance status (0/1/2-) 103/71/21. Treatment line (1st/2nd/more than 3rd): 17/26/152. Grade 3 or higher adverse events related to Pmab were hypomagnesemia (11.5%), rash acneiform (14.3%), paronychia (4.6%). Adverse events accounted for 7.3% of pts discontinuation, but there were no treatment-related deaths. Grade 3 or higher hypomagenesaemia and rash acneiform were observed more often in more than 3rd line treatment, compared to 1st or 2nd line treatment (1st or 2nd/3rd-, 1/ 17, p=0.128, 2/26, p= 0.05). Conclusions: Severe hypomagnesemia was observed more often in daily practice in Japan, compared with previous reports. Grade 3 or higher hypomagnesemia and rash acneiform were observed more often in more than 3rd line setting, compared with 1st or 2nd line settings.

Final STEPP results of prophylacatic versus reactive skin toxicity (ST) treatment (tx) for panitumumab (pmab)-related ST in patients (pts) with metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA4027-CRA4027 ◽  
Author(s):  
E. P. Mitchell ◽  
M. Lacouture ◽  
H. Shearer ◽  
N. Iannotti ◽  
B. Piperdi ◽  
...  
Keyword(s):  
Human Monoclonal Antibody ◽  
Life Quality ◽  
Topical Steroid ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Efficacy And Safety ◽  
The Us ◽  
Modified Recist ◽  
The Difference ◽  
Prophylactic Use

CRA4027 Background: Pmab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is approved as monotherapy in the US for mCRC following disease progression (PD) and in the EU and Canada for tumors bearing wild-type (WT) KRAS. The most common toxicity with anti-EGFR inhibitors are ST. This study of pmab+ chemotherapy (CT) estimates the difference in the incidence of specific ≥ grade 2 ST of interest between pts receiving prophylactic (P) or reactive (R) skin tx. Methods: Pts had unresectable mCRC after PD with 1st-line fluoropyrimidine and oxaliplatin-based CT ± bevacizumab. Pts received either pmab 6.0mg/kg/FOLFIRI Q2W or pmab 9 mg/kg/irinotecan Q3W. Within each stratum, pts were randomized 1:1 to either P ST tx 24 hrs before the 1st dose daily for 6 wks or R ST tx after ST occurred. Tx for ST included: moisturizers, sunscreen, topical steroid, and doxycycline. Efficacy and safety were evaluated by P vs R tx groups, KRAS status (mutant [MT] vs WT), and chemotherapy status. Responses were assessed using modified RECIST with confirmation. Quality of life was assessed using the Dermatology Life Quality Index at screening, wks 2–7, and follow-up. Results: 95 pts were enrolled and randomized: 48 pts to P and 47 pts to R. During the 6 wk ST tx period, 29% of pts in the P group vs 62% of pts in the R group had protocol-specified ≥grade 2 ST. Of the 87 KRAS evaluable pts, 49 (56%) pts had WT KRAS and 38 (44%) pts had MT KRAS. Efficacy and safety are shown. Mean (SD) change in DLQI from baseline was 1.3 (2.6) for P and 4.2 (5.8) for R at wk 3 (when the median time to 1st ≥grade 2 ST was reached in the R group) and was 2.0 (2.8) for P and 2.6 (4.4) for R at wk 7. Conclusions: Prophylactic use of the skin tx regimen resulted in >50% reduction in the rate of specific ≥ grade 2 STs and improved QOL during the 6-week skin tx period vs R use. Numerical differences in favor of the P group were observed for all endpoints. [Table: see text] [Table: see text]

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