On May 26, 2022 Amgen (NASDAQ: AMGN) reported that it will present new data from across its broad oncology innovative medicines and biosimilars portfolio and robust pipeline at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 3-7 in Chicago and virtually (Press release, Amgen, MAY 26, 2022, View Source [SID1234615068]).
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Oral presentations will showcase Amgen’s medicines for both lung and colorectal cancers with a plenary session highlighting the results from the PARADIGM Phase 3 head-to-head trial conducted by Takeda Pharmaceutical Company in Japan comparing the efficacy of Vectibix (panitumumab) versus Avastin (bevacizumab), both used in combination with chemotherapy, in patients with previously untreated RAS wild-type metastatic colorectal cancer (mCRC)*. Data from a pooled analysis of CodeBreaK 100, representing the largest evaluation of mechanisms of acquired resistance in KRASG12C inhibition, offer new insights to help inform combination treatment approaches with LUMAKRAS/ LUMYKRAS.
"Amgen continues to lead the science in KRASG12C inhibition and is committed to advancing research into how LUMAKRAS can improve outcomes for more patients, including further defining resistance patterns to guide our robust combination treatment development program," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "In addition, the compelling head-to-head results further reinforcing the important role Vectibix plays in the treatment of colorectal cancer, illustrate how Amgen is expanding the impact of our first-in-class therapies in some of the most challenging-to-treat cancers."
In the CodeBreaK 100 analysis, investigators evaluated patterns of resistance to LUMAKRAS in patients with NSCLC (n=67) and CRC (n=45) at disease progression. At least one newly acquired genomic alteration at progression was detected in 19 (28%) NSCLC patients and in 33 (73%) CRC patients. The alterations were heterogeneous in both tumor types, with variants detected across multiple genes and pathways.
Other research highlights being presented on Amgen Oncology’s growing precision medicine and T-cell engager pipeline include study updates on bemarituzumab, a potential first-in-class therapy for a subset of gastric and gastroesophageal cancers that overexpress fibroblast growth factor receptor 2 (FGFR2b), AMG 193, a small molecule methylthioadenosine (MTA) cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor being investigated for the treatment of solid tumors, and tarlatamab, an investigational, first-in-class half-life extended (HLE) bispecific T-cell engager (BiTE) molecule that is uniquely designed to target delta-like ligand 3 (DLL3) in neuroendocrine cancers.
Additional information on Amgen’s abstracts is available on the ASCO (Free ASCO Whitepaper) website.
Abstracts and Presentation Times:
Amgen Sponsored Abstracts
LUMAKRAS/LUMYKRAS (sotorasib)
Largest evaluation of acquired resistance to sotorasib in KRAS p.G12C-mutated non-small cell lung cancer (NSCLC) and colorectal cancer (CRC): plasma biomarker analysis of CodeBreaK 100
Abstract #102, Oral Presentation Session: Clinical Science Symposium, ctDNA: Dawn of a New Era, Saturday, June 4 from 8:00-9:30 a.m. CDT
First data for sotorasib in patients with pancreatic cancer with KRAS p.G12C mutation: a phase 1/2 study evaluating efficacy and safety
Abstract #360490, Plenary Series: Rapid Abstract Updates, Sunday, June 5 from 4:30-6:00 p.m. CDT
Trial-in-progress: A phase 2 study of sotorasib as first-line treatment in patients with stage IV non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS p.G12C mutation (CodeBreaK 201)
Abstract #TPS9150, Poster Presentation Session: Lung Cancer—Non-Small Cell Metastatic, Monday, June 6 from 8:00-11:00 a.m. CDT
IMLYGIC (talimogene laherparepvec)
Primary analysis of a phase 2, open-label, multicenter trial of talimogene laherparepvec (T-VEC) plus pembrolizumab (pembro) for the treatment (Tx) of patients (pts) with advanced melanoma (MEL) who progressed on prior anti–PD-1 therapy: MASTERKEY-115
Abstract #9518, Poster Discussion Session: Melanoma/Skin Cancers, Monday, June 6 from 4:30-6:00 p.m. CDT
Investigational BiTE Platform
Trial-in-progress: Phase 2 study of tarlatamab, a DLL3-targeting half-life extended bispecific T-cell engager (HLE BiTE) immuno-oncology therapy, in relapsed/refractory small cell lung cancer (SCLC)
Abstract #TPS8603, Poster Presentation Session: Lung Cancer-Non-small cell local-regional/small cell/other thoracic cancers, Monday, June 6 from 8:00-11:00 a.m. CDT
Trial-in-progress: A phase 1 study of AMG 509 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Abstract #TPS5101, Poster Session: Genitourinary Cancer—Prostate, Testicular, and Penile, Monday, June 6 from 1:15-4:15 p.m. CDT
AMG 193
Trial-in-progress: Design and rationale of a phase 1 dose-escalation study of AMG 193, a methylthioadenosine (MTA)-cooperative PRMT5 inhibitor, in patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors
Abstract #TPS3167, Poster Presentation Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology, Sunday, June 5 from 8:00-11:00 a.m. CDT
Bemarituzmab
Trial-in-progress: Phase 3 study of bemarituzumab + mFOLOFOX6 versus placebo + mFOLFOX6 in previously untreated advanced gastric or gastroesophageal junction (GEJ) cancer with FGFR2b overexpression (FORTITUDE-101)
Abstract #TPS4164, Poster Presentation: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary, Saturday, June 4 from 8:00-11:00 a.m. CDT
Trial-in-progress: Phase 1b/3 study of bemarituzumab + mFOLFOX6 + nivolumab vs mFOLFOX6 + nivolumab in previously untreated advanced gastric and gastroesophageal junction (GEJ) cancer with FGFR2b overexpression (FORTITUDE-102)
Abstract #TPS4165, Poster Presentation: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary, Saturday, June 4 from 8:00-11:00 a.m. CDT
Partner-Led Abstracts
Vectibix (panitumumab)
Plasma RAS dynamics and anti-EGFR rechallenge efficacy in patients with RAS/BRAF wild-type metastatic colorectal cancer: REMARRY and PURSUIT trials
Abstract #3518, Poster Discussion Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Resistance mechanisms to anti-EGFR therapy in RAS/RAF wildtype colorectal cancer varies by regimen and line of therapy
Abstract #3554, Poster Presentation: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with RAS wild-type metastatic colorectal cancer (mCRC): results from the phase 3 PARADIGM trial
Abstract #LBA1, Plenary Session: Primary Track: Special Sessions, Sunday, June 5 from 1:00-4:00 p.m. CDT
Prolia (denosumab)
Long-term outcomes of adjuvant denosumab in breast cancer: Fracture reduction and survival results from 3,425 patients in the randomised, double-blind, placebo-controlled ABCSG-18 trial
Abstract #507, Oral Presentation: Breast Cancer—Local/Regional/Adjuvant, Tuesday, June 7 from 9:45 a.m.-12:45 p.m. CDT
Investigator Sponsored Studies (ISS)
IMLYGIC (talimogene laherparepvec)
Trial-in-progress: Neo-adjuvant T-VEC plus nivolumab combination therapy for resectable early- stage or metastatic (IIIB-IVM1a) melanoma with injectable disease: The NIVEC trial
Abstract #TPS9607, Poster Session: Melanoma/Skin Cancers, Monday, June 6 from 1:15-4:15 p.m. CDT
KYPROLIS (carfilzomib)
A phase II study of daratumumab with weekly carfilzomib, pomalidomide, and dexamethasone in relapsed and refractory multiple myeloma
Abstract #8012, Poster Discussion Session: Hematologic Malignancies – Plasma Cell Dyscrasia, Saturday, June 4 from 4:30-6:00 p.m. CDT
ATLAS: A phase 3 randomized trial of carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma
Abstract #8001, Oral Abstract Session: Hematologic Malignancies—Plasma Cell Dyscrasia, Sunday, June 5 from 8:00-11:00 a.m. CDT
Daratumumab carfilzomib lenalidomide and dexamethasone as induction therapy in high-risk, transplant-eligible patients with newly diagnosed myeloma: Results of the phase 2 study IFM 2018-04
Abstract #8002, Oral Abstract Session: Hematologic Malignancies—Plasma Cell Dyscrasia, Sunday, June 5 from 8:00-11:00 a.m. CDT
LUMAKRAS/LUMYKRAS (sotorasib)
Trial-in-progress: A phase Ib/II study of sotorasib combined with chemotherapy for second-line treatment of KRAS p. G12C mutated advanced pancreatic cancer
Abstract #TPS4194, Poster Session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary, Saturday, June 4 from 8:00-11:00 a.m. CDT
Predictors of biomarker testing among patients (pts) with metastatic non-small cell lung cancer (mNSCLC)
Abstract #9130, Poster Session: Lung Cancer—Non-Small Cell Metastatic, Monday, June 6 from 8:00-11:00 a.m. CDT
Vectibix (panitumumab)
Phase 2 study of anti-EGFR rechallenge therapy with panitumumab with or without trametinib in advanced colorectal cancer
Abstract #3520, Poster Discussion Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Negative hyperselection for mutations associated with anti-EGFR antibody resistance in RAS wildtype metastatic colorectal cancer (mCRC): Evaluation of the PANAMA trial (AIO-KRK-0212, maintenance therapy with 5-FU, folinic acid (FU/FA) with or without panitumumab)
Abstract #3536, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Consensus molecular subtypes (CMS) as prognostic & predictive biomarkers of panitumumab (Pmab), fluorouracil & folinic acid (FU/FA) or FU/FA maintenance therapy following Pmab-FOLFOX induction in RAS wildtype metastatic colorectal cancer (mCRC) – PANAMA trial (AIO-KRK-0212)
Abstract #3537, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Impact of age and gender on the efficacy & safety of panitumumab plus fluorouracil & folinic acid versus fluorouracil and folinic acid alone as maintenance therapy in RAS WT metastatic colorectal cancer (mCRC). Subgroup analysis of the PANAMA-study (AIO-KRK-0212)
Abstract #3567, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Predictive and prognostic value of carcinoembryonic antigen (CEA) on maintenance therapy with 5-fluoruracil/leucovorin plus panitumumab or 5-fluoruracil/leucovorin alone in RAS wildtype metastatic colorectal cancer: Evaluation of the phase II PanaMa trial (AIO KRK 0212)
Abstract # 3587, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Modified FOLFOXIRI plus panitumumab (mFOLFOXIRI/PAN) versus mFOLFOX6/PAN as initial treatment of unresectable RAS and BRAF wild-type metastatic colorectal cancer (mCRC) patients: results of the phase III randomized TRIPLETE study by GONO
Abstract #LBA3505, Oral Presentation: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 9:45 a.m.–12:45 p.m. CDT
Randomized intermittent or continuous panitumumab plus FOLFIRI (FOLFIRI/PANI) for first-line treatment of patients (pts) with RAS/BRAF wild-type metastatic colorectal cancer (mCRC): the IMPROVE study
Abstract #3503, Oral Abstract Session: Gastrointestinal Cancer—Colorectal and Anal, Monday, June 6 from 9:45 a.m.-12:45 p.m. CDT
XGEVA (denosumab)
Trial-in-progress: A phase 3 study to determine the breast cancer risk reducing effect of denosumab in women carrying a germline BRCA1 mutation (BRCA-P Study)
Abstract #TPS10616, Poster Session: Prevention, Risk Reduction, and Hereditary Cancer, Monday, June 6 from 1:15-4:15 p.m. CDT
*Amgen out licenses Vectibix to Takeda in Japan.
About LUMAKRAS/LUMYKRAS (sotorasib)
Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.1 LUMAKRAS/LUMYKRAS has demonstrated a positive benefit-risk profile with rapid, deep, and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.2
Amgen is progressing the largest and broadest global KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, including triplets, with clinical trial sites spanning five continents. To date, over 4,000 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use.
In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval with its approval in the U.S., under accelerated approval. LUMAKRAS/LUMYKRAS is also approved in the European Union, Japan, United Arab Emirates, South Korea and Switzerland and in Australia, Brazil, Canada, and Great Britain under the FDA’s Project Orbis. Through Project Orbis, Amgen also has Marketing Authorization Applications (MAAs) for sotorasib in review in Israel and Singapore. Additionally, Amgen has submitted MAAs in Argentina, Colombia, Hong Kong, Kuwait, Malaysia, Mexico, Qatar, Saudi Arabia, Taiwan, Thailand and Turkey.
LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.3
About Non-Small Cell Lung Cancer and the KRAS G12C Mutation
Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.4 Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease and 5-year survival is only 8% for those with metastatic disease.5
KRAS G12C is the most common KRAS mutation in NSCLC.6 About 13% of patients with NSCLC harbor the KRAS G12C mutation.7 Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. The outcomes with other approved therapies are suboptimal, with a median progression-free survival of approximately four months following second-line treatment of KRAS G12C-mutated NSCLC.8
About CodeBreaK
The CodeBreaK clinical development program for Amgen’s drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.
CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.9 Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline.2 The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and results have been published.10
CodeBreaK 200, the global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in KRAS G12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated, locally advanced and unresectable or metastatic KRAS G12C-mutated NSCLC. The primary endpoint is progression-free survival and key secondary endpoints include overall survival, objective response rate, and patient-reported outcomes.11
Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.12 A Phase 2 randomized study will evaluate sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).13
For information, please visit www.hcp.codebreaktrials.com.
LUMAKRAS (sotorasib) U.S. Indication
LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.
This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
LUMAKRAS (sotorasib) Important U.S. Safety Information
Hepatotoxicity
LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis
LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions
The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.
Drug Interactions
Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.
Please see LUMAKRAS full Prescribing Information.
About Vectibix (panitumumab)
Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.
In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.
In June 2017, the FDA approved a refined indication for Vectibix for use in in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC.
INDICATION AND LIMITATION OF USE
Vectibix is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC): as first-line therapy in combination with FOLFOX, and as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.
Limitation of Use: Vectibix is not indicated for the treatment of patients with RAS mutant mCRC or for whom RAS mutation status is unknown.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].
In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures.
Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune- related effects (e.g., Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix concerning dermatologic toxicity are provided in the product labeling.
Vectibix is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS."
Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix and FOLFOX versus FOLFOX alone.
Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix treatment, periodically during Vectibix treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate.
In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions.
Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy.
Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix therapy. Discontinue Vectibix therapy if ILD is confirmed.
In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix versus the risk of pulmonary complications must be carefully considered.
Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix.
Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix for acute or worsening keratitis.
In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0).
NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix-treated patients. As a result of the toxicities experienced, patients randomized to Vectibix, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy.
Vectibix can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix.
In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.
The most commonly reported adverse reactions (≥ 20%) with Vectibix + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration.
To see the Vectibix Prescribing Information, including Boxed Warning visit www.vectibix.com.
About Amgen Oncology
At Amgen Oncology, our mission to serve patients drives all that we do. That’s why we’re relentlessly focused on accelerating the delivery of medicines that have the potential to empower all angles of care and transform lives of people with cancer.
For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.
At Amgen, we’re advancing oncology at the speed of life.