AstraZeneca recently announced that new data from the ADAURA trial regarding AGRISSO® (osimertinib) has been released.
The ADAURA trial is an ongoing study of TAGRISSO as adjuvant therapy after tumor resection in adult patients with completely resected Stage IB-IIIA EGFRm (exon 19 deletions or exon 21 L858R mutations) non-small cell lung cancer (NSCLC).
TAGRISSO was approved as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test on December 18, 2020.
Please see the Important Safety Information below and full Prescribing Information, including Patient Information.
IMPORTANT SAFETY INFORMATION
∙ There are no contraindications for TAGRISSO
∙ Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% of the 1479 TAGRISSO-treated patients; 0.3% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
∙ Heart rate-corrected QT (QTc) interval prolongation occurs in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
∙ Cardiomyopathy occurred in 3% of the 1479 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
∙ Keratitis was reported in 0.7% of 1479 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
∙ Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed
∙ Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
∙ Aplastic anemia has been reported in patients treated with TAGRISSO in clinical trials (0.07% of 1479) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated
∙ Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
∙ Most common (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough
INDICATIONS
TAGRISSO is a registered trademark of the AstraZeneca group of companies.
AstraZeneca recently announced that the US Food and Drug Administration (FDA) has approved a new indication for LYNPARZA® (olaparib) in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
LYNPARZA is the FIRST and ONLY PARPi approved in combination with abiraterone plus prednisone or prednisolone (abi/pred) as initial therapy for BRCAm mCRPC.
FDA approval was based on the results from the PROpel phase 3 trial, which was presented at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium and published in the journal NEJM Evidence (New England Journal of Medicine Group).
This is the eighth indication approved for LYNPARZA in the US.
For more information regarding the approval, please see AstraZeneca’s press release announcing the news.
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Seagen Announces FDA Accelerated Approval of TUKYSA® (tucatinib) in Combination with Trastuzumab for People with Previously Treated RAS Wild-Type, HER2-Positive Metastatic Colorectal Cancer
– First FDA-approved treatment in HER2-positive metastatic colorectal cancer –
– Combination regimen is approved for use in the second-line treatment setting and beyond –
BOTHELL, Wash.–(BUSINESS WIRE)– Seagen Inc. (Nasdaq: SGEN) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to TUKYSA® (tucatinib) in combination with trastuzumab for adult patients with RASwild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. TUKYSA is approved under the FDA’s Accelerated Approval Program based on tumor response rate and durability of response from the phase 2 MOUNTAINEER clinical trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. This is the first FDA-approved treatment in HER2-positive metastatic colorectal cancer. The FDA previously granted Breakthrough Therapy Designation and Priority Review for TUKYSA in this setting.
“Historically, patients with HER2-positive metastatic colorectal cancer who have progressed following frontline therapy have had poor outcomes,” said John Strickler, M.D., associate professor of medicine, Duke University Medical Center, and lead investigator for the MOUNTAINEER trial. “The FDA approval of a chemotherapy-free combination regimen that specifically targets HER2 is great news for these patients.”
“Biomarker testing is bringing new hope to people living with some types of colorectal cancer by opening the door to targeted treatments like TUKYSA for those who have RAS wild-type, HER2-positive disease,” said Michael Sapienza, CEO, Colorectal Cancer Alliance. “It is critical that physicians and patients understand the importance of comprehensive biomarker testing at diagnosis because it can inform treatment decisions and help improve outcomes.”
Results from the MOUNTAINEER trial showed a 38% overall response rate (ORR) (95% Confidence Interval [CI]: 28, 49) per blinded independent central review (BICR) in the patients who received TUKYSA in combination with trastuzumab (N=84 with a median age of 55.0 years [range: 24 to 77]). Complete responses were observed in 3.6% of patients (n=3), and partial responses were observed in 35% of patients (n=29). The median duration of response (DOR) per BICR was 12.4 months (95% CI: 8.5, 20.5). At study entry, 64% and 70% of these patients had liver or lung metastases, respectively.
The Prescribing Information for TUKYSA includes warnings and precautions for diarrhea, hepatotoxicity and embryo-fetal toxicity, some of which may be severe or fatal. In MOUNTAINEER, serious adverse reactions occurred in 22% of patients; the most common (in ≥2% of patients) were intestinal obstruction (7%), urinary tract infection (3.5%), pneumonia, abdominal pain and rectal perforation (2.3% each). The most common adverse reactions (≥20%) in patients treated with TUKYSA and trastuzumab were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions and pyrexia. Adverse reactions leading to permanent discontinuation of TUKYSA occurred in 6% of patients; the most common (in ≥2% of patients) was increased alanine aminotransferase (ALT) (2.3%). Please see additional Important Safety Information below.
“The accelerated approval of TUKYSA for RAS wild-type, HER2-positive metastatic colorectal cancer expands TUKYSA-based therapy to patients across two distinct types of cancer,” said Marjorie Green, M.D., Senior Vice President and Head of Late-Stage Development, Seagen. “We believe the efficacy and safety profile of the TUKYSA and trastuzumab-based regimen further establishes its role as an important backbone of dual HER2 inhibition in the treatment of adult patients with certain HER2-expressing breast and colorectal cancers.”
The FDA’s Accelerated Approval Program allows for approval of a medicine based on a surrogate endpoint that is reasonably likely to predict clinical benefit if the medicine fills an unmet medical need for a serious condition. A global, randomized phase 3 clinical trial (MOUNTAINEER-03) is ongoing and will compare TUKYSA in combination with trastuzumab and mFOLFOX6 with standard of care, which is intended to serve as a confirmatory trial and potentially support future global regulatory submissions. Merck, known as MSD outside of the U.S. and Canada, is commercializing TUKYSA in regions outside of the U.S., Canada and Europe and plans to discuss results from the MOUNTAINEER trial with certain health authorities as it continues to accelerate the filing of TUKYSA in its territories.
For more information, please see the full Prescribing Information for TUKYSA here .
Merck announces new treatment indication for KEYTRUDA®
Adjuvant Treatment Following Resection and Platinum-Based Chemotherapy for Adult Patients With Stage IB (T2a ≥4 cm), II, or IIIA NSCLC KEYTRUDA® (pembrolizumab) Injection 100 mg, as a single agent, is indicated for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 cm), II, or IIIA non–small cell lung cancer (NSCLC).
• KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.
• Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
• Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy. Immune-Mediated Pneumonitis.
Before prescribing KEYTRUDA® (pembrolizumab), please read the Prescribing Information.
Coverage to include serial monitoring in all subtypes, including hormone receptor-positive, HER2-positive, and triple negative breast cancers
Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, announced that it has received written confirmation from the Centers for Medicare & Medicaid Services’ (CMS) Molecular Diagnostics Services Program (MolDX) that Natera’s Signatera molecular residual disease (MRD) test has met coverage requirements for adjuvant and recurrence monitoring in patients with stage IIb or higher breast cancer. The coverage applies across all subtypes of the disease, including hormone receptor (HR)-positive, HER2-positive, and triple negative breast cancers. This decision adds to Medicare’s prior coverage of Signatera in colorectal cancer, muscle-invasive bladder cancer, and pan-cancer immunotherapy monitoring.
“Signatera is a critical innovation that can help us to enhance care management for patients with breast cancer,” said Jenny C. Chang, M.D., treating oncologist and director of the Houston Methodist Dr. Mary and Ron Neal Cancer Center. “The five-year recurrence rates for breast cancer are estimated to be as high as 30 percent,and traditional methods for detecting recurrence can be inaccurate. Signatera addresses a critical unmet need and improves our ability to accurately predict recurrence risk from breast cancer.”
The decision by CMS was primarily based on evidence from the Exploratory Breast Lead Interval Study (EBLIS), published in Clinical Cancer Research.1 In the study, patients with breast cancer across all subtypes were monitored with Signatera every 6 months after surgery, resulting in early relapse detection with 89% sensitivity, 100% specificity, and a diagnostic lead time of up to 2 years (median 8.9 months) ahead of radiographic imaging. Signatera MRD status was also found to be the most significant risk factor for recurrence across all subtypes of disease. This study is one of several that support the use of Signatera in breast cancer, and one of over 40 peer-reviewed publications across solid tumors.
“Extending Medicare coverage for Signatera to patients with breast cancer, irrespective of subtype, is a real milestone for precision oncology and a game changer for patients,” said Minetta Liu, M.D., chief medical officer of oncology at Natera. “Our tumor-informed assay enables oncologists to more confidently identify patients at high risk of recurrence, informing decisions related to active surveillance via imaging, as well as decisions to escalate or de-escalate treatment.”
To read the full press release or to learn more about Signatera™ click here
Pharmacyclics LLC, invites you to attend a Multidisciplinary Discussion during the 2022 ASH Annual Meeting on Incorporating Imbruvica® (ibrutinib) into treatment strategies. The program will be held on Monday December 12th from 8:00 to 9:00 AM in Exhibit Hall/Theater 7 during the ASH Annual Meeting. Session sponsored by Pharmacyclics LLC, an AbbVie company and Janssen Biotech, Inc.
TO RSVP, GO TO: https://portal.meintl.com/s/janssen-hcp-program?program=P0001907
Please note: Your e-mail address is required for registration. The information you provide will only be used to facilitate your attendance at this program.
AstraZeneca recently announced that the US Food and Drug Administration (FDA) has approved a new indication for IMFINZI® (durvalumab1,2 ), in combination with IMJUDO® (tremelimumab-actl), for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). 1,2
This approval is based on results from the HIMALAYA trial, a Phase III, global, randomized, open-label, multicenter study to assess the efficacy and safety of IMFINZI (an anti–PD-L1) + IMJUDO (an anti–CTLA-4) combination therapy vs sorafenib in the treatment of patients with uHCC that has not been previously treated and is not amenable to locoregional therapy. This new dual immuno-oncology combination therapy, known as the Single Tremelimumab Regular Interval Durvalumab (STRIDE) Regimen, is a single priming 300 mg dose of IMJUDO plus IMFINZI 1500 mg on Day 1, followed by IMFINZI 1500 mg every 4 weeks until disease progression or unacceptable toxicity.1-3
Hepatocellular carcinoma (HCC) is the most common form of liver cancer (accounting for about 85% to 90% of primary liver cancer cases) and is the third leading cause of cancer-related deaths in the world.4,5 The estimated 5-year overall survival for patients in the United States with metastatic and/or regional uHCC is no more than 11%.6
HCC is a heterogeneous disease associated with concomitant liver disease, cardiovascular health, and bleeding risk. More treatment options are needed to help address the complexity of HCC.7,8
The results of the HIMALAYA trial were published in the June 2022 issue of NEJM Evidence.3 Based on these results, the FDA granted IMFINZI, in combination with IMJUDO, priority review status in April 2022 and full approval on October 21, 2022.9,10
Please see the attached Sample Order Set Template for key information to help integrate this new indication into your institution’s EMR. This information is derived from the complete Prescribing Information for both IMFINZI and IMJUDO and the study protocol from the HIMALAYA trial.
This is the second approval for IMFINZI in gastrointestinal tumors.
Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO.
You may report side effects related to AstraZeneca products by clicking here.
The US Food and Drug Administration (FDA) has approved a new indication for IMFINZI® (durvalumab), in combination with gemcitabine and cisplatin, for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).1
BTCs comprise a heterogeneous group of rare cancers, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, that account for approximately 1% of all new cancer cases annually in the United States.2-5 The majority of BTCs (about 60% to 70%) are diagnosed as unresectable or metastatic disease,6 and more than 10 years have passed since gemcitabine plus cisplatin (gem-cis) was established as the standard of care in the first-line systemic treatment of advanced BTCs.7,8
IMFINZI, in combination with gem-cis, was studied in 685 patients with locally advanced or metastatic BTCs in the Phase III, randomized, double-blind, placebo-controlled, multicenter, global TOPAZ-1 trial, results of which were published in the June 2022 issue of NEJM Evidence.9 In this trial, IMFINZI + gem-cis demonstrated significant improvement in the primary endpoint of overall survival (OS) vs gem-cis + placebo1,9:
Serious adverse reactions occurred in 47% of patients receiving IMFINZI + gem-cis. The most frequent (≥2% of patients) were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%), and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI + gem-cis and included ischemic or hemorrhagic stroke (reported in 4 patients), sepsis, and upper gastrointestinal hemorrhage (reported in 2 patients each).1
Based on these results, the FDA granted IMFINZI, in combination with gem-cis, priority review status in May 2022 and full approval on September 2, 2022 —making it the first [and only] FDA-approved regimen for the first-line treatment of patients with locally advanced or metastatic BTCs.1,10,11
Additionally, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatobiliary Cancers recommend durvalumab (IMFINZI®) in combination with gemcitabine + cisplatin as a Category 1, preferred systemic therapy option for primary treatment of patients with unresectable or metastatic BTCs.12†
INDICATIONS
Please see complete Prescribing Information including Medication Guide.
You may report side effects related to AstraZeneca products by clicking here.
Thanks to @SenatorLankford, the Medicare #MCED Screening Coverage Act now has 51 cosponsors in the Senate! This bill is a must-pass for Oklahoma seniors, who deserve to access the best possible tools to detect cancer early.
On August 24, 2022, the Food and Drug Administration approved ibrutinib (Imbruvica, Pharmacyclics LLC) for pediatric patients ≥ 1 year of age with chronic graft versus host disease (cGVHD) after failure of 1 or more lines of systemic therapy. Formulations include capsules, tablets, and oral suspension.
For more information, read the FDA Announcement or Press Release.
