Safety and efficacy of panitumumab (pmab) in HPV-positive (+) and HPV-negative (-) recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Analysis of the global phase III SPECTRUM trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5504-5504 ◽  
Author(s):  
Jan Stoehlmacher-Williams ◽  
Cristian Villanueva ◽  
Paolo Foa ◽  
Sylvie Rottey ◽  
Eric Winquist ◽  
...  
Keyword(s):  
Human Monoclonal Antibody ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Geographic Region ◽  
Phase Iii ◽  
Asia Pacific ◽  
Background Spectrum ◽  
Safety And Efficacy ◽  
Platinum Based Chemotherapy ◽  
Hpv Status

5504^ Background: SPECTRUM evaluated the safety and efficacy of pmab, a fully human monoclonal antibody against the epidermal growth factor receptor, with platinum‑based chemotherapy (CT) vs CT alone in patients (pts) with R/M SCCHN. This predefined analysis presents outcomes by tumor HPV status. Methods: All tumor samples were centrally reviewed. HPV status was determined using a validated immunohistochemistry assay to p16INK4A by an independent lab blinded to treatment assignments. Tumor samples were scored positive or negative according to prespecified criteria. Results: Of 657 enrolled pts (ITT), 443 (67%) had samples evaluable for HPV testing. Ninety‑nine (22%) tumors were HPV+ and 344 (78%) were HPV-. HPV+ rates varied by site (37% oropharynx, 19% larynx, 15% oral cavity, and 13% hypopharynx) and geographic region (44% N America, 22% W Europe, 21% Asia Pacific, 19% S America, and 18% E Europe). Demographics were generally balanced except pts with HPV+ vs HPV- tumors were more often non‑smokers (31% vs 14%), had oropharyngeal tumors (47% vs 23%), and had poorly differentiated tumors (30% vs 13%). Efficacy results are shown (Table). Adverse events were generally balanced between HPV+ and HPV- pts. Conclusions: Pts with HPV- R/M SCCHN administered pmab + CT had improved overall survival (OS) and progression‑free survival (PFS), whereas no improvement in OS or PFS was observed in pts with HPV+ tumors. [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.

Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial

2007 ◽  
Vol 25 (12) ◽  
pp. 1545-1552 ◽  
Author(s):  
Ulrich Gatzemeier ◽  
Anna Pluzanska ◽  
Aleksandra Szczesna ◽  
Eckhard Kaukel ◽  
Jaromir Roubec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Double Blind

Purpose Erlotinib is a potent inhibitor of the epidermal growth factor receptor tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of erlotinib in combination with cisplatin and gemcitabine as first-line treatment for advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1). The primary end point was overall survival (OS). Secondary end points included time to disease progression (TTP), response rate (RR), duration of response, and quality of life (QoL). Results A total of 1,172 patients were enrolled. Baseline demographic and disease characteristics were well balanced. There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment arms. In a small group of patients who had never smoked, OS and progression-free survival were increased in the erlotinib group; no other subgroups were found more likely to benefit. Erlotinib with chemotherapy was generally well tolerated; incidence of adverse events was similar between arms, except for an increase in rash and diarrhea with erlotinib (generally mild). Conclusion Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC.

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION primary analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5545-5545
Author(s):  
Andres Poveda ◽  
Stephanie Lheureux ◽  
Nicoletta Colombo ◽  
David Cibula ◽  
Kristina Lindemann ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Progression Free Survival ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Phase Iii ◽  
Primary Analysis ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib ◽  
Grade 3

5545 Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including non-BRCAm pts. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 prior lines of platinum-based chemotherapy (PBC), we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and were in complete response (CR) or partial response (PR) to PBC. Pts received maintenance olaparib (tablets; 300 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). Secondary endpoints included PFS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status determined by central Myriad tumor and germline testing; and time to first subsequent treatment (TFST). The primary analysis was planned for 18 months (mo) after the last patient was enrolled. Results: 279 pts were enrolled from 17 countries (mean age: 64 years); 253 pts (90.7%) were confirmed non-gBRCAm. At data cut-off (Oct 2, 2020), median PFS was 9.2 mo (95% CI 7.6–10.9), with 210 PFS events (75.3% maturity). 65.3%, 38.5% and 24.3% of pts were progression-free (PF) at 6, 12 and 18 mo, respectively. The Table shows PFS in key subgroups. Median TFST was 13.9 mo (95% CI 11.5–16.4). Median exposure to olaparib was 9.4 mo (range 0.0–31.9). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 29.0% of pts and serious TEAEs in 19.7% of pts. TEAEs led to dose interruption, dose reduction and treatment discontinuation in 47.0%, 22.6% and 7.5% of pts, respectively. Conclusions: Our findings support the use of olaparib maintenance therapy in non-gBRCAm PSR OC pts, consistent with our interim analysis and previous trials in this setting. Clinical trial information: NCT03402841. [Table: see text]

Addition of Aflibercept to Fluorouracil, Leucovorin, and Irinotecan Improves Survival in a Phase III Randomized Trial in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen

2012 ◽  
Vol 30 (28) ◽  
pp. 3499-3506 ◽  
Author(s):  
Eric Van Cutsem ◽  
Josep Tabernero ◽  
Radek Lakomy ◽  
Hans Prenen ◽  
Jana Prausová ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Survival Times ◽  
Previously Treated

Purpose Treatment for metastatic colorectal cancer (mCRC) commonly involves a fluoropyrimidine-based chemotherapy regimen such as infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) or fluorouracil, leucovorin, and oxaliplatin, often combined with bevacizumab or an epidermal growth factor receptor monoclonal antibody. We studied the effect of adding the novel antiangiogenic agent aflibercept (also known as ziv-aflibercept in the United States) to FOLFIRI in patients with mCRC previously treated with oxaliplatin, including patients who received prior bevacizumab. Patients and Methods Patients were randomly assigned to receive aflibercept (4 mg/kg intravenously; 612 patients) or placebo (614 patients) every 2 weeks in combination with FOLFIRI. Treatment was administered until disease progression or unacceptable toxicity. The primary end point was overall survival. Results Adding aflibercept to FOLFIRI significantly improved overall survival relative to placebo plus FOLFIRI (hazard ratio [HR], 0.817; 95.34% CI, 0.713 to 0.937; P = .0032) with median survival times of 13.50 versus 12.06 months, respectively. Aflibercept also significantly improved progression-free survival (PFS; HR, 0.758; 95% CI, 0.661 to 0.869; P < .0001), with median PFS times of 6.90 versus 4.67 months, respectively. The effects on overall survival and PFS exhibited a consistent trend across prespecified subgroup analyses, including bevacizumab pretreated patients. Response rate was 19.8% (95% CI, 16.4% to 23.2%) with aflibercept plus FOLFIRI compared with 11.1% (95% CI, 8.5% to 13.8%) with placebo plus FOLFIRI (P = .0001). Adverse effects reported with aflibercept combined with FOLFIRI included the characteristic anti–vascular endothelial growth factor effects and also reflected an increased incidence of some chemotherapy-related toxicities. Conclusion Aflibercept in combination with FOLFIRI conferred a statistically significant survival benefit over FOLFIRI combined with placebo in patients with mCRC previously treated with oxaliplatin.

Targeted Therapy in Combination with Chemotherapy in Recurrent and/or Metastatic Head and Neck Cancer

2010 ◽  
Vol 06 (01) ◽  
pp. 43
Author(s):  
Pol Specenier ◽  
Jan B Vermorken ◽  
◽  
Keyword(s):  
Monoclonal Antibodies ◽  
Tyrosine Kinase ◽  
Head And Neck ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Platinum Based Chemotherapy ◽  
Pathway Inhibition

Two epidermal growth factor receptor (EGFR)-targeting strategies are used in recurrent and/or metastatic squamous cell cancer of the head and neck (SCCHN): monoclonal antibodies and small-molecule tyrosine kinase inhibitors. Thus far, the monoclonal antibody cetuximab has been studied in most detail. Based on the results of two randomised phase III trials, cetuximab in combination with platinum-based chemotherapy should be considered the new standard first-line regimen for patients with recurrent and/or metastatic disease for whom a platinum-based regimen regimen is considered the best treatment option. Other EGFR-directed monoclonal antibodies are under investigation. The role of EGFR tyrosine kinase inhibitors (TKIs) in SCCHN is less well established and early data on other targeted agents have also been disappointing thus far. Dual pathway inhibition may overcome resistance to single pathway inhibition.

Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing low (1–9%) or negative (<1%) levels of epidermal growth factor receptor (EGFr)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3547-3547 ◽  
Author(s):  
J. Hecht ◽  
E. Mitchell ◽  
J. Baranda ◽  
I. Malik ◽  
D. Richards ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Response Duration ◽  
Infusion Reaction ◽  
Prior Therapy ◽  
Epidermal Growth ◽  
Tumor Expression

3547 Background: Panitumumab is a fully human monoclonal antibody directed against EGFr. We investigated the antitumor activity of panitumumab in pts with mCRC who failed prior therapy and had low or negative EGFr tumor expression. Methods: In this multicenter, phase 2 study of 150 planned pts, pts had documentation of disease progression (PD) during or after adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin (centrally confirmed refractory disease [CCRD]), 2–3 prior regimens, ECOG score 0–2, and low or negative EGFr staining (by IHC) in evaluable tumor cells. Pts received panitumumab at 6 mg/kg Q2W until PD or drug intolerability. Tumor assessments (modified WHO, blinded central review) were taken periodically from wk 8 until PD. Endpoints were objective response (OR) through wk 16 (+ ≥ 4 wk confirmation; primary) and OR throughout study, response duration, progression-free survival (PFS) time, survival time, and safety (secondary). Results: In this interim analysis (6/05), 88 pts were enrolled and had ≥ 1 dose of panitumumab (safety set); 23 pts had ≥ 20 wks before the cutoff and CCRD (efficacy set). The efficacy set consisted of 16M/7W, median age of 65 (range: 46, 85) yrs, 83% white, 100% with ECOG ≤ 1, 74% colon cancer and 26% rectal cancer; all received ≥ 2 prior regimens (equivalent characteristics for safety set). 2/11 (18%) pts with EGFr-negative tumors and 1/12 (8%) with low EGFr staining had a partial response. Duration was up to 16 wks. 7/23 (30%) of all pts had SD. Median (95% CI) PFS was 7.9 (7.0, 23.0) wks. In the safety set, all pts had a treatment-related adverse event; 19% grade (gr) 3; 2% gr 4. Integument and eye toxicities were: 92% skin, 17% eye, 28% nail, 8% hair, and 2% chelitis. 20 (23%) had diarrhea (1 gr 3); 7 (8%) had hypomagnesemia (2 gr 3/4). Three pts had an infusion reaction-1 gr 3 (led to panitumumab discontinuation) and 2 gr 1/2. In 65 pts with both a baseline and post-baseline sample, no human anti-human antibodies to panitumumab were detected. Updated data will be presented. Conclusions: Responses to panitumumab were seen in pts with mCRC with both low and negative EGFr levels. Efficacy appears similar to that in other studies with panitumumab in pts with higher EGFr tumor levels. [Table: see text]

Cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil (5-FU) in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R&M SCCHN) (EXTREME)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5537-5537 ◽  
Author(s):  
J. B. Vermorken ◽  
R. Mesia ◽  
M. E. Vega-Villegas ◽  
E. Remenar ◽  
R. Hitt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Prognostic Significance ◽  
Safety Data ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Safety Analysis ◽  
Data Safety Monitoring Board ◽  
Phase Iii

5537 Background: The epidermal growth factor receptor (EGFR) is expressed in nearly all SCCHN and carries a strong prognostic significance, providing the rationale for using EGFR-targeted agents, such as cetuximab, in this indication. This study assesses the efficacy and safety of cetuximab in combination with chemotherapy commonly used in the treatment of R&M SCCHN. Methods: Patients (pts) were enrolled into this phase III trial from December 2004 to December 2005 and randomized either to Group A: cetuximab (first dose 400 mg/m2 then 250 mg/m2 weekly) plus a maximum of 6 three-weekly cycles of cisplatin (100 mg/m2 IV on day 1) or carboplatin (AUC 5, day 1) and 5-FU (1000 mg/m2/day continuous infusion for the first 4 days of each cycle) or to Group B: cisplatin or carboplatin with 5-FU as before. Cetuximab was administered until progression or unacceptable toxicity. Primary endpoint is overall survival time; secondary endpoints are progression-free-survival, response rate, disease control rate, safety, and Quality of Life. It was planned to randomize a total number of 420 pts in order to detect a difference in improvement in overall survival of 2.5 months. Results: At the end of the recruitment,440 pts have been randomized, to date 320 pts are under treatment, 21 have withdrawn from the study and 99 have completed the study. The Data Safety Monitoring Board (DSMB) has performed an independent preplanned safety analysis from the first 140 pts, 138 pts of whom were treated. Patients were followed for a minimum of 6 weeks: M/F122/16, median age57 years [range, 38–79],median Karnofsky performance status (KPS) 80 [range, 70–100]. In this safety analysis, there were 14 deaths, none of which were treatment related. The most frequent drug related grade 3–4 toxicity was mainly represented by neutropenia, thrombocytopenia and anemia. Conclusions: The DSMB evaluated baseline and safety data, found no reason to stop the trial and recommended continuation of the study. [Table: see text]

Phase III randomized trial of pegylated liposomal doxorubicin (PLD) plus carboplatin versus carboplatin in platinum-sensitive (PS) patients with recurrent epithelial ovarian or peritoneal carcinoma after failure of initial platinum-based chemotherapy: Southwest Oncology Group Protocol S0200

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5551-5551 ◽  
Author(s):  
D. S. Alberts ◽  
P. Y. Liu ◽  
S. Wilczynski ◽  
M. Clouser ◽  
A. Lopez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Response Rates ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Carboplatin Auc ◽  
Patient Accrual

5551 Background: There is a continuing debate over the role of combination, platinum-based chemotherapy for PS, recurrent ovarian cancer (OC). Although this phase 3 trial was closed prematurely by the SWOG Data Safety and Monitoring Committee (DSMC) due to slow patient accrual, it provided provocative results nonetheless. Methods: Patients with recurrent stage III or IV OC, with a progression-free and platinum-free interval of 6- 24 months after completion of first-line platinum-based chemotherapy, and up to 12 courses of non-platinum containing chemotherapy or biologic therapy as consolidation treatment after the first-line regimen were eligible and observed for progression-free survival (PFS) and overall survival (OS). Patients were randomized to either IV PLD (30 mg/m2) plus IV carboplatin (AUC=5 mg/mL × min) once every 4 weeks (PLD arm) or IV carboplatin (AUC=5mg/ML × min) once every four weeks alone. Results: The PLD arm enrolled 31 patients and the carboplatin alone arm enrolled 30 for a total of 61 patients out of the 900 planned. The response rates were 67% (18/27) for the PLD arm and 32% (9/28) for the carboplatin only arm (Fisher’s exact p=0.02). The estimated median PFS on the PLD arm was 12 months and 8 months on the carboplatin only arm. The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm (p=0.02). 26% of the patients on the PLD arm reported grade 4 toxicities, all hematological in nature. Conclusions: Although this study was closed early, because of slow patient accrual the results for the PLD arm are intriguing for response rates, median progression-free survival and overall survival. These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS, recurrent disease. No significant financial relationships to disclose.

SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8001-8001 ◽  
Author(s):  
F. Cappuzzo ◽  
T. Ciuleanu ◽  
L. Stelmakh ◽  
S. Cicenas ◽  
A. Szczesna ◽  
...  
Keyword(s):  
Disease Control ◽  
Primary Endpoint ◽  
Advanced Nsclc ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Double Blind ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

8001 Background: Erlotinib (E), a small-molecule EGFR TKI, is proven to extend survival versus placebo (P) in 2nd/3rd-line advanced NSCLC. The phase III SATURN study (BO18192) was initiated to evaluate E as maintenance therapy after standard 1st-line platinum-based chemotherapy (CT) in advanced NSCLC. Methods: Patients with no evidence of disease progression after 4 cycles of CT were randomized to receive either E 150 mg/day or P until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) in all patients and the co-primary endpoint was PFS in EGFR immunohistochemistry-positive (IHC+) patients. Results: A total of 1,949 patients entered the CT phase, of whom 889 were randomized to E (n=438) or P (n=451). Median age was 60 years for both arms. Baseline characteristics for E and P arms (%): male/female: 73/27 and 75/25; adenocarcinoma + BAC/squamous-cell/other: 47/38/15 and 44/43/13; stage IIIB/IV: 26/74 and 24/76; Caucasian/Asian/other: 84/14/2 and 83/15/2; ECOG PS 0/1: 31/69 and 32/68; current/former/never smoker: 55/28/18 and 56/27/17. PFS (by investigator assessment; confirmed by independent review) was significantly prolonged with E versus P in all patients (HR 0.71 [95% CI 0.62–0.82]; p<.0001) and in EGFR IHC+ patients (HR 0.69 [95% CI 0.58–0.82]; p<.0001). Subgroup analyses will be reported. Response rate was 12% with E versus 5% with P. Disease control rate (complete response + partial response + stable disease >12 wks) was 40.8% with E versus 27.4% with P (p<.0001). OS data are not yet mature. E was well tolerated: the majority of treatment-related adverse events (AEs) were grade 1/2. AEs reported in ≥10% of all patients were rash (60% with E versus 9% with P) and diarrhea (20% with E versus 5% with P); again, most were grade 1/2. Only 2.3% of patients receiving E had a serious treatment-related AE and 2.8% withdrew due to a treatment-related AE. Conclusions: The SATURN study met its primary and co-primary endpoints with high statistical significance. Erlotinib in the 1st-line maintenance setting is well tolerated, and significantly improves disease control and delays progression versus placebo across patient subgroups. [Table: see text]

Mutant (MT) KRAS codon 12 and 13 alleles in patients (pts) with metastatic colorectal cancer (mCRC): Assessment as prognostic and predictive biomarkers of response to panitumumab (pmab).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3581-3581 ◽  
Author(s):  
Marc Peeters ◽  
Jean-Yves Douillard ◽  
Eric Van Cutsem ◽  
Salvatore Siena ◽  
Kathy Zhang ◽  
...  
Keyword(s):  
Human Monoclonal Antibody ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Allele Distribution ◽  
Three Phase ◽  
Epidermal Growth ◽  
Codon 12 And 13 ◽  
Kras Codon

3581 Background: Pmab is a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR). Significant improvement in progression-free survival (PFS) was demonstrated in pts with wild-type (WT) KRAS mCRC treated with pmab+FOLFOX4 (1st-line; study 20050203), pmab+FOLFIRI (2nd-line; study 20050181), and pmab monotherapy (study 20020408). In mCRC, mutations in KRAS codons 12 and 13 are established biomarkers for lack of clinical benefit to anti-EGFR therapies. We retrospectively examined individual MT KRAS codon 12 and 13 alleles as prognostic and predictive biomarkers of response in three phase 3 studies. Methods: Pts were randomized to receive FOLFOX4, FOLFIRI, or best supportive care +/- pmab 6.0 mg/kg Q2W in trials 20050203, 20050181, and 20020408, respectively. The MT KRAS codon 12 and 13 alleles (G12A, G12C, G12D, G12R, G12S, G12V, G13D) were detected using the Therascreen K-RAS Mutation Kit (Qiagen). Results: MT KRAS codon 12 and 13 alleles were detected in 40% (440/1096), 45% (486/1083), and 43% (184/427) of pts in trials 20050203, 20050181, and 20020408, respectively. MT KRAS allele distribution was conserved across studies and balanced between treatment arms. Baseline demographic and clinical features were comparable between all MT KRAS allele subgroups. There was no consistent evidence that any individual MT KRAS allele, compared to the remaining MT KRAS alleles or the entire MT KRAS group, differentially impacted PFS or overall survival (OS) in control arm-treated or pmab-treated pts. Only in the pmab+FOLFOX4 arm of study 20050203 were G13D (unfavorably) and G12V (favorably) significantly associated with OS. Response rates were similar between MT KRAS allele groups in the 1st- and 2nd-line mCRC treatment setting. Finally, in analyses of pts pooled from all 3 trials, only the G12A KRAS allele emerged as a significant negative predictive factor for OS. Conclusions: The lack of consistent results across three lines of therapy indicates pts whose tumors harbor MT KRAS codon 12 or 13 alleles are unlikely to respond to pmab therapy. Currently, only pts with WT KRAS mCRC should be treated with EGFR antibodies.

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