Cetuximab and irinotecan (CPT11) salvage treatment for colorectal cancer (CRC) in progression after two or more chemotherapy (CT) lines: The POLONORD Group experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14575-14575 ◽  
Author(s):  
D. Fagnani ◽  
A. Bertolini ◽  
E. Menatti ◽  
M. Duro ◽  
G. Luchena ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Cutaneous Toxicity ◽  
Free Survival ◽  
Epidermal Growth ◽  
Control Disease ◽  
Evaluating Methods ◽  
And Control

14575 Background: Cetuximab is a monoclonal antibody blocking the Epidermal Growth Factor Receptor (EGFR), that showed activity in advanced CRC. His safety and therapeutic profile in clinical practice is still carefully evaluating. Methods: 7 Italian Oncology Units (PoloNord Group) treated, from December 2004 to December 2006, 72 patients (pts) affected by metastatic (mts) CRC, in progression after two or more previous CT lines, with Cetuximab + CPT11 ± Fluorouracil (5FU). Cetuximab initial dose was 400 mg/m2, followed by 250 mg/m2 as weekly infusion; dose adjustments based on cutaneous toxicity. Median courses: 12 (range 2–59). CPT11 and 5FU was administered according centres favourite schedules. We evaluated pts for safety, objective response (RO), progression free survival (PFS) and overall survival (OS) Results: Pts characteristics: M/F 48/25; median age 64 years (range 39–74); previous chemotherapy lines: 2–6 (Oxaliplatin and CPT11± 5FU); EGFR positive: 72. Mts sites: liver 56%, lung 21%, peritoneum 10%; 13% of pts had two or more mts sites. Safety: 8/72 (11%) pts showed G3–4 toxicity (WHO): cutaneous 5 pts; vomiting 1 pts, and neutropenia 3 pts . No allergic reactions. 4/72 pts stopped therapy to unacceptable toxicity, while 53/72 pts to disease progression. RO in 68/72 pts were: 9 RP (13%), 14 SD (21%) and 45 PD (66%). 6/14 SD pts showed tumor markers (CEA/Ca19.9) reduction. No pts had surgery option after treatment. Median PFS from start of therapy in 58/72 pts was 4 months (range 1–15). Median OS from diagnosis of mts disease in 67/72 pts was 28 months (range 7–81). Conclusions: According to safety and control disease reporting by international trials, our experiences showed that, also in clinical practice, Cetuximab + CPT11 is a valid option for the treatment of advanced, pretreated CRC. No significant financial relationships to disclose.

scholarly journals Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102

2018 ◽  
Vol 36 (16) ◽  
pp. 1556-1563 ◽  
Author(s):  
Noah Kornblum ◽  
Fengmin Zhao ◽  
Judith Manola ◽  
Paula Klein ◽  
Bhuvaneswari Ramaswamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival ◽  
Er Positive ◽  
Epidermal Growth

Purpose The mammalian target of rapamycin inhibitor everolimus targets aberrant signaling through the PI3K/AKT/mammalian target of rapamycin pathway, a mechanism of resistance to anti-estrogen therapy in estrogen receptor (ER)–positive breast cancer. We hypothesized that everolimus plus the selective ER downregulator fulvestrant would be more efficacious than fulvestrant alone in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase II study included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2–negative, AI-resistant metastatic breast cancer randomly assigned to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo. The study was designed to have 90% power to detect a 70% improvement in median progression-free survival from 5.4 months to 9.2 months. Secondary end points included objective response and clinical benefit rate (response or stable disease for at least 24 weeks). Prophylactic corticosteroid mouth rinses were not used. Results The addition of everolimus to fulvestrant improved the median progression-free survival from 5.1 to 10.3 months (hazard ratio, 0.61 [95% CI, 0.40 to 0.92]; stratified log-rank P = .02), indicating that the primary trial end point was met. Objective response rates were similar (18.2% v 12.3%; P = .47), but the clinical benefit rate was significantly higher in the everolimus arm (63.6% v 41.5%; P = .01). Adverse events of all grades occurred more often in the everolimus arm, including oral mucositis (53% v 12%), fatigue (42% v 22%), rash (38% v 5%), anemia (31% v. 6%), diarrhea (23% v 8%), hyperglycemia (19% v 5%), hypertriglyceridemia (17% v 3%), and pneumonitis (17% v 0%), although grade 3 to 4 events were uncommon. Conclusion Everolimus enhances the efficacy of fulvestrant in AI-resistant, ER-positive metastatic breast cancer.

Predictors of prolonged benefit from palbociclib (PAL) plus fulvestrant (F) in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer (ABC) in PALOMA-3.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1050-1050 ◽  
Author(s):  
Massimo Cristofanilli ◽  
Angela DeMichele ◽  
Carla Giorgetti ◽  
Dennis J. Slamon ◽  
Seock-Ah Im ◽  
...  
Keyword(s):  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Free Survival ◽  
Molecular Features ◽  
Hormone Receptor Positive ◽  
Epidermal Growth ◽  
Intent To Treat ◽  
Term Benefit

1050 Background: PAL+F improved progression-free survival (PFS) over F + placebo (P) in patients (pts) with endocrine-resistant HR+/HER2– ABC. We examined factors predictive of long-term benefit on PAL+F. Methods: Pre/postmenopausal pts with HR+/HER2– ABC that progressed on prior endocrine therapy (ET) were randomized 2:1 to PAL (125 mg/d oral [3 wk on, 1 wk off]) + F (500 mg) or P+F. Characteristics of pts with prolonged benefit (treatment [tx] duration ≥18 mo for PAL+F; ≥12 mo for P+F based on median PFS and tx duration) were compared with the intent-to-treat (ITT) population. Results: PAL+F improved PFS vs P+F (11.2 vs 4.6 mo; hazard ratio, 0.50). By Aug 2016, 138 pts had long-term benefit: 100/347 (29%) pts on PAL+F received tx for ≥18 mo, including 70 (20%) who received > 2 y (26–39 cycles). In contrast, 38/174 (22%) pts on P+F received ≥12 mo of tx; only 16 (9%) received > 2 y (27–38 cycles). No apparent differences in baseline characteristics of pts with long-term benefit were observed between groups except that a greater proportion of those on P+F had a single site of disease involvement (40% PAL+F vs 63% P+F). Pts with long-term benefit on PAL+F had lower rates of visceral disease (42% vs 60%), liver metastases (18% vs 40%), and ≥3 disease sites (27% vs 39%) at baseline vs the ITT population; no difference in sensitivity to prior ET was observed (84% vs 79%). Objective response rate (ORR) was higher among pts with prolonged benefit on PAL+F vs ITT (36% vs 26%). Conclusions: PAL+F is associated with prolonged benefit in about a third of pts treated with the combination in PALOMA-3. These pts achieve higher ORR compared to other study pts and the benefit is independent of baseline site and number of metastatic recurrences and prior endocrine sensitivity. Benefit from F alone is less prolonged and appears limited to those with 1 site of disease involvement. The analysis confirms the efficacy of PAL+F in HR+ ABC with visceral recurrence. Biomarker analyses are ongoing in pts with long-term benefit to understand molecular features predictive of tx sensitivity. Funding: Pfizer. Clinical trial information: NCT01942135.

scholarly journals Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 434 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Jen-Yu Hung ◽  
Mei-Hsuan Lee ◽  
Chia-Yu Kuo ◽  
Yu-Chen Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
Younger Patients ◽  
Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

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]

RAS mutations and their correlation with survival of patients with advanced pancreatic adenocarcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 325-325
Author(s):  
Thiago Lins Almeida ◽  
Jessica Ribeiro Gomes ◽  
Marcel Cerqueira Cesar Machado ◽  
Antonio C. Buzaid ◽  
Fernando C. Maluf
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Predictive Factor ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Free Survival ◽  
First Line Therapy ◽  
Ras Status ◽  
Epidermal Growth

325 Background: The prognosis of pancreatic adenocarcinoma (PA) remains poor despite FOLFIRINOX and nab-paclitaxel-gemcitabine based chemotherapy. The epidermal growth factor receptor (EGFR) has a major role in pancreatic cancer carcinogenesis.The RAS status showed to be a predictive factor for response to anti-EGFR therapy in colon cancer. We aim to analyze the K-RAS and N-RAS status in PA and its prognostic impact. Methods: Retrospective analysis included 24 patients with metastatic (67%) or locally advanced (29%) PA at diagnosis (AEMOC, Brazil). K-RAS and N-RAS profile were performed by polymerase chain reaction and bidirectional sequencing (codons 12, 13, 61, 117, 146). The results were then analyzed in regards to overall survival (OS) and progression-free survival (PFS) in PA. Results: The sample showed: median age of 63 years (28-86), 62.5% male, 45.8% smoker, head site (67%), ductal (68%), and mild differentiation features (45%). The first-line therapy was FOLFIRINOX (62.5%) and gemcitabine (33.3%). The median PFS and OS were 6.5 and 13 months (mo), respectively. Nineteen patients (79.1%) presented mutation in K-RAS: four c.35G>A (G12D), four c.34G>C (G12R), four c.35G>T (G12V), three c.35G>C (G12A), one c.437C>T (A146V), and one c.34G>T (G12C). Mutation in N-RAS (c.38G>A (G13D) was detected in only one patient (4%). The only independent factor for survival was K-RAS status: the c.35G>A (G12D) polymorphism yielded worse PFS and OS when compared to non-c.35G>A (G12D) mutation: 3 vs 7 mo [HR 0.25, 95% CI, (0.04–1.63)] for PFS (p<0,0043) and 3.5 vs13 mo [HR 0.17, 95% CI, 0.01-1.58)] for OS (p<0,0001), respectively. Conclusions: K-RAS was the only prognostic factor for PFS and OS, with the polymorphism c.35G>A (G12D) being related to a worse prognostic. Further studies are necessary to better evaluate whether K-RAS and N-RAS status is prognostic and/or predictive factor.

scholarly journals Immunologic Escape After Prolonged Progression-Free Survival With Epidermal Growth Factor Receptor Variant III Peptide Vaccination in Patients With Newly Diagnosed Glioblastoma

2010 ◽  
Vol 28 (31) ◽  
pp. 4722-4729 ◽  
Author(s):  
John H. Sampson ◽  
Amy B. Heimberger ◽  
Gary E. Archer ◽  
Kenneth D. Aldape ◽  
Allan H. Friedman ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Delayed Type Hypersensitivity ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Epidermal Growth

Purpose Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed in normal tissues but widely expressed in glioblastoma multiforme (GBM) and other neoplasms. Patients and Methods A phase II, multicenter trial was undertaken to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival (PFS) and overall survival (OS) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease. Intradermal vaccinations were given until toxicity or tumor progression was observed. Sample size was calculated to differentiate between PFS rates of 20% and 40% 6 months after vaccination. Results There were no symptomatic autoimmune reactions. The 6-month PFS rate after vaccination was 67% (95% CI, 40% to 83%) and after diagnosis was 94% (95% CI, 67% to 99%; n = 18). The median OS was 26.0 months (95% CI, 21.0 to 47.7 months). After adjustment for age and Karnofsky performance status, the OS of vaccinated patients was greater than that observed in a control group matched for eligibility criteria, prognostic factors, and temozolomide treatment (hazard ratio, 5.3; P = .0013; n = 17). The development of specific antibody (P = .025) or delayed-type hypersensitivity (P = .03) responses to EGFRvIII had a significant effect on OS. At recurrence, 82% (95% CI, 48% to 97%) of patients had lost EGFRvIII expression (P < .001). Conclusion EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III, randomized trial.

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