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.

scholarly journals Epidermal Growth Factor Receptor Inhibitors: A Review of Cutaneous Adverse Events and Management

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
K. Chanprapaph ◽  
V. Vachiramon ◽  
P. Rattanakaemakorn
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adverse Events ◽  
Current Knowledge ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Maculopapular Rash ◽  
Postinflammatory Hyperpigmentation ◽  
Epidermal Growth

Epidermal growth factor inhibitors (EGFRI), the first targeted cancer therapy, are currently an essential treatment for many advance-stage epithelial cancers. These agents have the superior ability to target cancers cells and better safety profile compared to conventional chemotherapies. However, cutaneous adverse events are common due to the interference of epidermal growth factor receptor (EGFR) signaling in the skin. Cutaneous toxicities lead to poor compliance, drug cessation, and psychosocial discomfort. This paper summarizes the current knowledge concerning the presentation and management of skin toxicity from EGFRI. The common dermatologic adverse events are papulopustules and xerosis. Less common findings are paronychia, regulatory abnormalities of hair growth, maculopapular rash, mucositis, and postinflammatory hyperpigmentation. Radiation enhances EGFRI rash due to synergistic toxicity. There is a positive correlation between the occurrence and severity of cutaneous adverse effects and tumor response. To date, prophylactic systemic tetracycline and tetracycline class antibiotics have proven to be the most effective treatment regime.

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]

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.

Interim analysis of the fierce-21 phase 2 (P2) study of vofatamab (B-701), a selective inhibitor of FGFR3, as salvage therapy in metastatic urothelial carcinoma (mUC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4547-4547 ◽  
Author(s):  
Begona Mellado ◽  
Daniel E. Castellano ◽  
S Pang ◽  
Yuksul Urun ◽  
Se Hoon Park ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Low Frequency ◽  
Skin Toxicity ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Grade 3 ◽  
Reported Data ◽  
Fgfr3 Mutations

4547 Background: Patients (pts) with mUC with FGFR3 mutations who have failed platinum-based chemotherapy have a poor prognosis. Their response to immune checkpoint inhibitors appears diminished 10% or less compared to WT pts. 20% of mUC pts harbor FGFR3 mutations or fusions (M/F). Vofatamab is a fully human monoclonal antibody against FGFR3 that blocks activation of the wildtype and genetically activated receptor. FIERCE-21 is a Phase 1b/2 study designed to evaluate vofatamab monotherapy (VFM) or in combination with docetaxel (VFD). Methods: The P2 expansion enrolled mUC pts with FGFR3 M/F+ tumor (identified with FoundationONE CDx™), who failed ≥ 1 prior line of chemotherapy (including prior taxane for pts receiving VFM) or recurred ≤ 12 months of (neo)adjuvant chemotherapy. Pts had measurable disease and ECOG ≤ 1. Treatment consisted of vofatamab at 25 mg/kg alone and in combination with docetaxel at 75 mg/m2 q3w. Efficacy was assessed by investigators (RECIST 1.1). Primary objectives were safety and objective response-rate (ORR). Results: In the P2, 21 pts each received VFM and VFD. 57% of VFD pts had received at least 2, and 71% of VFM at least 3 prior lines of therapy. Best response to prior therapy was PD for 67% of VFD and 38% of VFM. The safety profile is consistent with previously reported data. TEAEs occurring in > 20% of pts were decreased appetite, diarrhea, pyrexia, asthenia, anemia, dyspnea, and fatigue. Most common vofatamab-related TEAEs in > 10% of pts were asthenia, diarrhea, decreased appetite and rash; all were Grade 1 or 2. In VFM, only 1 pt had a grade 3 TEAE and no pt discontinued treatment due to an AE. There were no cases of hyperphosphatemia, ocular or nail toxicity; 1 pt reported grade 2 skin toxicity. For pts receiving VM, median age was 70 yrs, ECOG 1 = 67%, Hgb < 10 g/dL 5%, liver metastases 19%. Responses have been seen in 7 pts to date including those receiving both VFM and VFD. Conclusions: Vofatamab both alone and combined with D in a q3w schedule are well tolerated with a low frequency of grade 3 TEAEs. Both VFM and VFD have demonstrated efficacy in terms of ORR. PFS/OS and DOR data will be presented at 7+ months for VFD and 9+ months for VFM. Clinical trial information: NCT02401542.

Pan Canadian Rash Trial: A Randomized Phase III Trial Evaluating the Impact of a Prophylactic Skin Treatment Regimen on Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor–Induced Skin Toxicities in Patients With Metastatic Lung Cancer

2016 ◽  
Vol 34 (8) ◽  
pp. 810-815 ◽  
Author(s):  
Barbara Melosky ◽  
Helen Anderson ◽  
Ronald L. Burkes ◽  
Quincy Chu ◽  
Desiree Hao ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Phase Iii ◽  
Epidermal Growth ◽  
Third Line ◽  
Grade 3 ◽  
Line Setting

Purpose Erlotinib is an epidermal growth factor receptor inhibitor approved for patients with advanced non–small-cell lung cancer (NSCLC) whose epidermal growth factor receptor expression status is positive or unknown. Although it is efficacious, erlotinib can cause skin toxicity. This prospective, randomized phase III trial examined the effect of prophylactic treatment of erlotinib-induced skin rash. Patients and Methods Patients receiving erlotinib in the second- or third-line setting for advanced NSCLC were randomly assigned to prophylactic minocycline (100 mg twice per day for 4 weeks), reactive treatment (after rash developed, per grade of rash), or no treatment unless severe (grade 3). Rash incidence and severity, time to maximal rash, time to resolution, and overall survival (OS) were compared among treatment groups. Results In all, 150 patients were randomly assigned, 50 to each of three treatment arms. The incidence of skin toxicity was 84% regardless of treatment arm. Prophylactic treatment with minocycline significantly lengthened the time to the most severe grade of rash. Grade 3 rash was significantly higher in the no-treatment arm. OS was not significantly different among treatment arms, but patients receiving prophylactic or reactive treatments had a longer OS (7.6 and 8 months, respectively) than those who received no rash treatment (6 months). Rash was not self-limiting. Conclusion The incidence of all grades of rash did not differ statistically among the three arms, so the trial was negative. The incidence of grade 3 skin toxicities was reduced in patients who were treated with prophylactic minocycline or reactive treatment. Efficacy was not compromised. Prophylactic minocycline and reactive treatment are both acceptable options for the necessary treatment of erlotinib-induced rash in the second- or third-line setting of metastatic NSCLC.

Institutional experiences with panitumumab monotherapy in metastatic colorectal cancer (mCRC) patients (pts) intolerant to cetuximab

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14579-14579 ◽  
Author(s):  
A. D. Langerak ◽  
E. Mitchell ◽  
P. Cheema ◽  
G. L. River ◽  
M. Shing
Keyword(s):  
Additional Data ◽  
Growth Factor Receptor ◽  
Cross Reactivity ◽  
Compassionate Use ◽  
Pain Anxiety ◽  
Intravenous Saline ◽  
Life Threatening ◽  
Infusion Reactions ◽  
Epidermal Growth ◽  
Grade 3

14579 Background: Two monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor are approved for the treatment (tx) of advanced mCRC - panitumumab (Vectibix™), a fully human mAb, and cetuximab (Erbitux®), a chimeric mAb. Potential for cross-reactivity between these two mAbs with regard to infusion reactions (IR) has not been fully explored. Given the lack of sequence homology between the 2 agents and the fully human nature of panitumumab, it is hypothesized that pts intolerant to cetuximab due to IR could be tolerant to panitumumab. Methods: Single pt tx IND applications to administer panitumumab monotherapy in pts with advanced mCRC were approved by the FDA and local institutions as part of the Panitumumab Compassionate Use program. Eligibility also included previous tx with standard chemotherapy and intolerability to cetuximab, ie. CTCAE v3.0 grade 3 (severe) or grade 4 (life-threatening) IR. Results: Upon informed consent, 4 pts (2M/ 2F) were enrolled in 4 centers. Median (range) age was 62.5 (52, 64) years. 3 pts had colon cancer and 1 pt had rectal cancer. All had surgery and received prior 5-fluorouracil, leucovorin, irinotecan, oxaliplatin, bevacizumab, and cetuximab. One pt had a CTC grade 3 IR and 3 pts had a CTC grade 4 IR to cetuximab. IR symptoms included fever, wheezing, dyspnea, chest/back/abdominal pain, anxiety, hypotension, flushing, tachycardia, and tachypnea. Two IRs occurred within 10 minutes of the first cetuximab infusion. Cetuximab was discontinued and IR symptoms were treated with bronchodilators, diphenhydramine, epinephrine, methylprednisolone, oxygen, intravenous saline, and hospitalization. All pts received panitumumab. Data for pts 1, 2, and 3 are available: pt 1 received 1 infusion of panitumumab at 5 mg/kg Q2W with premedication (diphenhydramine and methylprednisolone); pts 2 and 3 received 7 and 2 panitumumab infusions, respectively, at 6 mg/kg Q2W without premedication. No pt had an IR to panitumumab. Pt 2 had stable disease; pts 1 and 3 died due to disease progression. Conclusions: Panitumumab monotherapy was tolerated without incidence of an IR in these cases of mCRC pts who are intolerant to cetuximab due to a severe or life-threatening IR. Additional data will be presented. No significant financial relationships to disclose.

Use of BIBW 2992, a novel irreversible EGFR/HER2 tyrosine kinase inhibitor (TKI), to treat patients with HER2-positive metastatic breast cancer after failure of treatment with trastuzumab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1023-1023
Author(s):  
T. Hickish ◽  
D. Wheatley ◽  
N. Lin ◽  
L. Carey ◽  
S. Houston ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Bibw 2992 ◽  
Epidermal Growth ◽  
Grade 3 ◽  
Positive Breast Cancer

1023 Background: BIBW 2992 (Tovok) is an oral, novel, and potent, irreversible dual epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) inhibitor, with preclinical activity in trastuzumab-resistant cell lines overexpressing HER2 and phase I clinical activity. A phase II study of BIBW 2992 in patients with HER2-positive breast cancer who have failed treatment with trastuzumab is currently being conducted in the US and the UK. Methods: This is a multi-institutional open label single arm phase II study, planning to recruit 40 patients. Eligibility criteria include stage IIIB or IV HER2-positive metastatic breast cancer, progression following receipt of trastuzumab or intolerance of trastuzumab, measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 and adequate organ function. Patients receive 50 mg BIBW 2992 once daily until disease progression. Tumor assessments are performed every two courses (one course = 28 days). The primary endpoint is objective response rate (RECIST criteria). Safety data are also collected. Results: To date, 40 patients have started treatment on the trial. Patients had received a median of three lines of prior therapy. Nine patients discontinued treatment prior to the first assessment at 8 weeks; four due to disease progression, four due to adverse events and one due to withdrawal of consent. Twenty-one patients have had tumor assessment after 8 weeks of treatment. Of these, four patients had a partial response (PR) and 10 patients had stable disease (SD). The PR has been confirmed at 16 weeks in one patient. The most frequently observed side effects to date are rash (Common Toxicity Criteria for Adverse Events [CTCAE] grade 3 in 4 patients) and diarrhea (CTCAE grade 3 in 8 patients). There were 20 dose reductions in 17 patients. Conclusions: BIBW 2992 at 50 mg/day induced responses and seems promising in HER2-positive breast cancer patients who have failed treatment with trastuzumab. Manageable cutaneous adverse events and diarrhea were the main side effects. [Table: see text]

Phase I Study of Anti–Epidermal Growth Factor Receptor Antibody Cetuximab in Combination With Radiation Therapy in Patients With Advanced Head and Neck Cancer

2001 ◽  
Vol 19 (13) ◽  
pp. 3234-3243 ◽  
Author(s):  
Francisco Robert ◽  
Mark P. Ezekiel ◽  
Sharon A. Spencer ◽  
Ruby F. Meredith ◽  
James A. Bonner ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Radiation Therapy ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adverse Events ◽  
Head And Neck ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Loading Dose ◽  
Epidermal Growth

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of a chimeric anti–epidermal growth factor receptor monoclonal antibody, cetuximab, in combination with radiation therapy (RT) in patients with advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: We treated 16 patients in five successive treatment schedules. A standard dose escalation procedure was used; three patients entered onto the study at each dose level of cetuximab received conventional RT (70 Gy, 2 Gy/d), and the final three patients received hyperfractionated RT (76.8 Gy, 1.2 Gy bid). Cetuximab was delivered as a loading dose of 100 to 500 mg/m2, followed by weekly infusions of 100 to 250 mg/m2 for 7 to 8 weeks. Circulating levels of cetuximab during therapy were determined using a biomolecular interaction analysis core instrument. Human antichimeric antibody response was evaluated with a double-antigen radiometric assay. The recommended phase II/III dose was defined as the optimal cetuximab dose level based on the pharmacologic parameters and adverse events. RESULTS: The most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities (grade 1 to 2 in most patients). Skin toxicity outside of the RT field was not strictly dose-dependent; however, grade 2 or higher events were observed in patients treated with higher dose regimens. There was one grade 4 allergic reaction. Most acute adverse effects were associated with RT (xerostomia, mucositis, and local skin toxicity). No antibodies against cetuximab were detected. All patients achieved an objective response (13 complete and two partial remissions). CONCLUSION: Cetuximab can be safely administered with RT. The recommended dose for phase II/III studies is a loading dose of 400 to 500 mg/m2 and a maintenance weekly dose of 250 mg/m2.

558 Programmed death (PD)-1 and PD-ligand-1 inhibitors in the treatment of non-small cell lung cancer: a systematic review of their efficacy and safety

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A592-A592
Author(s):  
Melissa Lingohr-Smith ◽  
Chelsea Deitelzweig ◽  
Grace Lin ◽  
Jay Lin
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Patient Outcomes ◽  
Nsclc Patient ◽  
Response Rates ◽  
Phase Iii ◽  
Combination Therapies ◽  
Phase Iii Clinical Trials ◽  
Programmed Death ◽  
Grade 3

BackgroundTreatment advances have been made in non-small cell lung cancer (NSCLC) with the development and approval of programmed death (PD)-1 and PD-ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1 inhibitors may be used as monotherapies or in combination with other agents and have been shown to improve NSCLC patient outcomes in clinical trials. We conducted a systematic search to compare the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of NSCLC.MethodsA systematic literature search of PubMed was conducted to identify phase III clinical trials in which the efficacy of PD-1/PD-L1 inhibitors in the treatment of NSCLC was evaluated. PD-1 inhibitors included nivolumab and pembrolizumab; PD-L1 inhibitors included atezolizumab, avelumab, and durvalumab. Patient characteristics and efficacy data were extracted.ResultsSixteen phase III clinical trials were identified (nivolumab=4; pembrolizumab=5; atezolizumab=5; avelumab=1; durvalumab=1). Across the 3 nivolumab monotherapy trials (n=638; median ages: 61–63 years), median progression-free survival (PFS) ranged 2.3–4.2 months; response rates ranged 19%-26%; grade 3/4 adverse events occurred in 7%-18% of patients. Nivolumab in combination with iplimumab (n=583; median age: 64 years) had a median PFS of 5.1 months and response rate of 33%; grade 3/4 adverse events occurred in 33% of patients. Across the 3 pembrolizumab monotherapy trials (n=1,481; median ages: 63–64 years), median PFS ranged 3.9–10.3 months; response rates ranged 18%-45%; grade ≥3 adverse events occurred in 13%-27% of patients. In the 2 pembrolizumab combination therapy trials (n=688; median ages: 65 years), median PFS ranged 6.4–8.8 months; response rates ranged 48%-58%; grade ≥3 adverse events occurred in 67%-70% of patients. In the 4 atezolizumab combination therapy trials (n=1,486; median ages: 63–64 years), median PFS ranged 6.3–8.3 months; response rates ranged 47%-63.5%; grade 3/4 adverse events occurred in 54%-73% of patients. In the 3 monotherapy trials of atezolizumab (n=613; median age: 63 years), avelumab (n=396; median age: 64 years), and durvalumab (n=476; median age: 64 years), the median months of PFS were 2.7, 2.8, and 17.2, respectively; response rates were 14%, 15%, and 30%, respectively; grade ≥3 adverse events occurred in 15%, 10%, and 30.5% of patients, respectively.ConclusionsAlthough treatment responses varied, most of the evaluated PD-1/PD-L1 inhibitors were associated with a clinical benefit for NSCLC trial patients. Generally, treatment efficacy was greater with combination therapies, but adverse events occurred more frequently. Innovations in the targeting/personalization of PD-1/PD-L1 combination therapies will likely lead to improved NSCLC patient outcomes and further research is needed in this regard.

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