Written By: Julia Stevens, PharmD, BCOP and Emmeline Academia, PharmD, BCOP Beth Israel Deaconess Medical Center

DOWNLOAD HERE

Description: Fibroblast growth factor receptor (FGFR) inhibitors are a class of oral oncolytics approved for certain FGFR-altered malignancies, including bladder cancer (erdafitinib) and cholangiocarcinoma (infigratinib and pemigatinib). FGFR inhibitors come with unique adverse effect profiles and monitoring considerations. The purpose of this PQI is to provide multidisciplinary team members with key education, monitoring, and supportive care considerations for patients on these therapies.

Background: The FGFR family of proteins (FGFR 1-4) are transmembrane tyrosine kinase signaling proteins with several physiologic functions including cell proliferation, differentiation, embryogenesis, angiogenesis and phosphate homeostasis.1 FGFR mutations and fusions can drive cancer growth via increased cell proliferation and survival, angiogenesis, and resistance to anticancer agents.2 The first FDA-approved FGFR inhibitor, erdafitinib is a pan-FGFR inhibitor indicated for advanced or metastatic urothelial carcinoma with susceptible FGFR 2 or 3 genetic mutations and translocations after progression on at least 1 platinum-containing chemotherapy.3 Erdafitinib demonstrated an objective response rate of 40% in the phase II BCL2001 trial.4 Both pemigatinib and infigratinib inhibit FGFR 1-3 and are approved for previously treated, unresectable advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement. Pemigatinib demonstrated a 36% objective response rate in the FGFR2-altered population of the phase II FIGHT-202 trial.5 Infigratinib yielded a 19% objective response rate patients with FGFR2 fusions in a phase II trial.6 All three agents were approved under the accelerated approval pathway, with final approval pending results of phase III trials.

Due to the unique physiologic roles of FGFR kinases, FGFR inhibitors have unique toxicity profiles. Hyperphosphatemia is a key on-target adverse effect of the FGFR inhibitors and requires specific monitoring. Furthermore, hyperphosphatemia may predict superior outcomes – erdafitinib requires a dose increase for those who do not experience hyperphosphatemia to optimize its efficacy.7 Other side effects also deserve attention including ocular toxicities, dermatologic toxicities, diarrhea, and fatigue. Each of these agents also carries the risk for fetal harm due to the role of FGFR in embryonal development.

PQI Process: Upon receipt of an order for an FGFR inhibitor:

  • Review patient’s history, including diagnosis and prior treatments
  • Verify the presence of a susceptible FGFR alteration for that drug or malignancy
    • Erdafitinib: select FGFR2 fusions, FGFR3 fusions, or FGFR3 mutations
    • Pemigatinib and infigratinib: select FGFR2 fusions or other arrangements
  • Assess baseline renal and hepatic function and need for any initial dose reductions (Table 1)
  • Review concomitant medications for interactions, dose adjustments, or spacing as appropriate
  • Evaluate pregnancy status prior to use in females of reproductive potential: counsel females and males with female partners of reproductive potential on appropriate contraception due to risk of fetal harm
  • Ensure ophthalmologic exams at baseline and at appropriate intervals throughout treatment (Table 1)

Patient Centered Activities:

  • Provide Oncology Chemotherapy Education (OCE) sheet for appropriate FGFR inhibitor to patient
  • Review dosing schedule and calendar with patient
  • Discuss signs and symptoms of hyperphosphatemia: muscle cramps, numbness, tingling in the mouth
  • For patients on erdafitinib, discuss implementing a low-phosphate diet before the initial dose increase period (14-21 days) with a goal of less than 600 – 800 mg phosphate in a day3 and should also avoid medications that increase phosphate including supplements, vitamin D, and some antacids
    • High phosphate foods: dairy, beans, lentils, processed meats, nuts, sodas with phosphates
    • Low phosphate foods: fresh fruits and vegetables, rice, fish, breads, pasta
  • Discuss dry eye and symptoms of ocular toxicity (central serous retinopathy/retinal pigment epithelial detachment): blurred vision, loss of vision, or other visual changes
  • Provide expectations for lab monitoring when starting therapy, especially during the first 2-3 months
  • Review dosing with patients as dose reductions occur to ensure proper administration
  • Medications should be stored in a cool, dry place at room temperature
  • FGFR inhibitors should be taken at about the same time each day *If a dose is missed, doses should not be doubled, they should be logged, and reported to the provider
  • Patient assistance

References:

  1. Mahipal A, Tella SH, Kommalapati A, Yu J, Kim R. Prevention and treatment of FGFR inhibitor-associated toxicities. Crit Rev Oncol Hematol. 2020;155:103091. doi:10.1016/j.critrevonc.2020.103091.
  2. Touat M, Ileana E, Postel-Vinay S, André F, Soria J-C. Targeting FGFR Signaling in Cancer. Clin Cancer Res. 2015;21(12):2684-2694. doi:10.1158/1078-0432.CCR-14-2329.
  3. Balversa. Package Insert. Janssen Products, LP; 2020.
  4. Loriot Y, Necchi A, Park SH, et al. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2019;381(4):338-348. doi:10.1056/NEJMoa1817323.
  5. Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21(5):671-684. doi:10.1016/S1470-2045(20)30109-1.
  6. Makawita S, K Abou-Alfa G, Roychowdhury S, et al. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Future Oncol. 2020;16(30):2375-2384. doi:10.2217/fon-2020-0299.
  7. Tagawa S, Siefker-Radtke A, Dosne A-G, et al. Hyperphosphatemia due to erdafitinib (a pan-FGFR Inhibitor) and anti-tumour activity among patients (Pts) with advanced urothelial carcinoma (UC). Ann Oncol. 2019;30:v375. doi:10.1093/annonc/mdz249.031
  8. Pemazyre. Package Insert. Incyte Corporation.
  9. Truseltiq. Package Insert. QED Therapeutics, Inc.

 

Supplemental Information:

Table 1. Dosing and Monitoring Guideline Summary

 Erdafitinib (Balversa®)3Pemigatinib (Pemazyre®)8Infigratinib (Truseltiq™)9
FDA IndicationAdvanced or metastatic urothelial carcinoma with susceptible FGFR2 or 3 genetic mutations after at least 1 platinum- containing chemotherapyUnresectable advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement, after previous treatmentUnresectable advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement, after previous treatment
Dosing8 mg (2 x 4 mg tablet) PO daily

Increase dose to 9 mg (3 x 3 mg tablet) daily after 14-21 days if phosphate < 5.5 mg/dL and no ocular or grade ≥ 2 toxicity.

Take with or without food

13.5 mg (1 x 13.5 mg tablet) PO daily for 14 consecutive days of a 21-day cycle.

Take with or without food

125 mg (1 x 100 mg plus 1 x 25 mg capsules) PO daily for 21 consecutive days of a 28-day cycle

Administer on an empty stomach at least 1 hour before or 2 hours after food

Dosage forms3 mg, 4 mg, 5 mg tablet4.5 mg, 9 mg, 13.5 mg tablet100 mg, 25 mg capsule
Dose reductions8 mg → 6 mg → 5 mg → 4 mg → discontinue13.5 mg → 9 mg → 4.5 mg → discontinue125 mg → 100 mg → 75 mg → 50 mg → discontinue
Use in organ dysfunctionRenal impairment: No adjustment required

Hepatic impairment: No adjustment required

Renal impairment: Dose reduction required for eGFR < 30 mL/min/1.73m2

Hepatic impairment: Dose reduction required for bilirubin >3 times ULN

Renal impairment: Dose reduction required for CrCl 30-89 mL/min, for CrCl < 30mL/min specific recommendations are not established

Hepatic impairment: Dose reduction required for bilirubin or AST above ULN

Pregnancy Use contraception during
treatment and for 1 month after last dose
Use contraception during treatment and for 1 week after last doseUse contraception during treatment and for 1 month after last dose
Drug-Drug or Food-Drug interactionsCYP3A4 and CYP2C9 inducers and inhibitors

Restrict phosphate intake to 600 to 800 mg daily during the initial dose adjustment period. Avoid vitamin D supplements, antacids, phosphate-containing enemas or laxatives, or other medications with phosphate excipients

CYP3A4 inducers and inhibitorsCYP3A4 inducers and inhibitors

Avoid use with PPIs. If H2RAs must be used, administer infigratinib 2 hours before or 10 hours after. Administer infigratinib 2 hours before or after mineral antacids

Take on an empty stomach due to increased absorption with food

Monitoring
Serum phosphateBaseline, day 14-21, then monthly

Median time to onset: 20 days

As clinically necessary (monitor weekly if hyperphosphatemia develops)

Median time to onset: 8 days

As clinically necessary (monitor weekly for serum phosphate >5.5 mg/dL)

Median time to onset: 8 days

Eye exams, including optical coherence tomographyBaseline, monthly x 4 months, then every 3 months thereafter and as clinically necessary

Median time to onset: 50 days

Baseline, every 2 months x 6 months, then every 3 months thereafter and as clinically necessary

Median time to onset: 62 days

Baseline, at 1 month, at 3 months, then every 3 months thereafter and as clinically necessary

Median time to onset: 26 days

Common adverse drug reactionsFatigue, onycholysis, alopecia, paronychia, stomatitis, diarrhea/constipation, decreased appetite, dysgeusia, nausea

Increased ALT, AST, alkaline phosphatase, creatinine, phosphate

Decreased sodium, albumin, magnesium, hemoglobin

Alopecia, nail changes, constipation/diarrhea, dysgeusia, nausea, decreased appetite, fatigue

Increased serum creatinine, ALT, AST, bilirubin, calcium, glucose

Decreased albumin, sodium

Alopecia, nail changes, abnormal eyelash growth, constipation/diarrhea, decreased appetite, dysgeusia, fatigue, epistaxis

Increased phosphate, triglycerides, creatinine

Decreased sodium, ALT, AST, alkaline phosphatase, bilirubin

 

Table 2. Clinical Trial Summary

 Patient PopulationDescriptionOutcome
BLC2001 StudyLocally advanced or metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 alterations

 

ErdafitinibObjective tumor response 40%

Median duration of PFS 5.5 months

Median duration of OS 13.8 months

FIGHT-202 StudyUnresectable, locally advanced, metastatic cholangiocarcinoma with FGFR2 fusion or rearrangementPemigatinibObjective tumor response 35.5%

Median DOR 7.5 months (5.7-14.5 months)

CBGJ398X2204 StudyPreviously treated, unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangementInfigratinibORR 23.1% (95% CI 15.6-32.2)

Median DOR 5.0 months (0.9-19.1 months)

PFS: Progression Free Survival, OS: Overall Survival, DOR: Duration of Response, ORR: Overall Response Rate

Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional.  This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented.  NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.
Read More

Written By: Neal Dave, PharmD, and Natasha Khrystolubova, RPh, BCOP
Download Here

Description: Management of adverse effects related to regorafenib treatment in metastatic colorectal cancer. Optimal dosing and follow up are essential to help patients benefit fully while taking this medication.

Background: Regorafenib is a multikinase inhibitor that has shown an overall survival benefit (6.4 months, regorafenib + supportive care versus 5.0 months, placebo + supportive care; CORRECT Trial) in the third line setting.  Keeping patients on therapy can be challenging due to the adverse effect profile* of multikinase inhibitors. The ReDOS trial evaluated the dose escalation strategy in regorafenib patients and efficacy. A strategy with weekly dose escalation of regorafenib from 80 mg to 160 mg/day (Arm A) was found to be superior to a starting dose of 160 mg/day (Arm B). A trend for improved OS was seen in the dose escalation arm. The dose escalation strategy did not appear to compromise QOL. Patients started on 80mg for the first week with weekly dose escalations in the absence of significant drug-related toxicities. Median Overall Survival (OS) was improved in Arm A vs. Arm B (9.8 months vs. 6.0 months; HR 0.72, 95% CI, p=0.12). Median Progression Free Survival (PFS) was 2.8 months for Arm A vs. 2.0 months for Arm B (HR 0.84, CI 95%, p=0.38).

PQI Process: Upon receipt of a new prescription for regorafenib:

  • If the typical starting dose of 160 mg by mouth once daily is written, exercise clinical judgement and contact prescriber to discuss and potentially start patient on a dose escalation schedule such as the one described (ReDOS trial strategy):
    • Document follow up schedule and dose escalation in EMR
    • Initiate patient at 80 mg for the first week of cycle 1
    • If no significant drug-related toxicities, escalate to 120 mg for the second week of cycle 1, otherwise hold therapy at current dose
    • If no significant drug-related toxicities, escalate to 160 mg for the third week of cycle 1, otherwise hold therapy at current dose
    • For following cycles, start therapy at current tolerated dose (no dose escalation)
  • Coordinate and establish a weekly follow up call with the patient or caregiver for the first 8 weeks
  • Monitor LFTs at baseline, every 2 weeks (for first 2 months) and then at least monthly thereafter
  • Educate patients on side effects and report adverse effects to prescriber and recommend dose adjustments in 40 mg increments as tolerated2

Patient Centered Activities:

  • Ensure patient knows dosing schedule (once daily for 3 weeks on and 1 week off)
  • Ensure patient knows to take dose with a low-fat meal (< 600 calories and 30% fat)
  • Only open 1 bottle of Regorafenib at a time *medication expires 7 weeks after bottle is opened
    • Packaging now available in 21 count bottle
  • Ensure patient or caregiver is able to take and record blood pressure at home weekly
  • Consider anti diarrheal and moisturizing cream
  • Patient Assistance: NCODA Financial Assistance Tool

 

Supplemental Information:

*Dose limiting side effects include (percentage refers to all grades)1:

Skin and subcutaneous tissue adverse events, including palmar-plantar erythrodysesthesia (Hand and Foot syndrome) 72%, diarrhea 43%, hypertension 30%, fatigue 64%, increased LFTs (AST-65%, ALT-45%, Bilirubin-45%).  The median time to first adverse event was 2 weeks with worst incidences occurring at 3 weeks. The worst severity of diarrhea occurred at 4 weeks. Increases in LFTs usually occur within the first 8 weeks of therapy.

 

References:

  1. Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381(9863):303-312.
  2. NCCN Clinical Practice Guidelines in Oncology (NCCN guidelines®) for colon cancer v.2.2018. © Page COL-D 9 of 10. National Comprehensive Cancer Network 2018. All rights reserved. Accessed May 10, 2018.
  3. STIVARGA® (Regorafenib) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, April 2017.
  4. Bekaii-Saab TS, Ou F-S, Ahn DH, et al. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study [published online June 28, 2019].Lancet Oncol. doi: 10.1016/S1470-2045(19)30272-4.

 

Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional. This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented. NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.

 

Read More
image-title

November 12, 2021

 

Statement From NCODA Legislative & Policy Advisory Committee
Contact: Kevin Scorsone | NCODA Legislative & Policy Liaison
(919) 903-2057
kevin.scorsone@ncoda.org

FOR IMMEDIATE RELEASE

 

Comment On Proposed LCD DL37810

Genomic Sequence Analysis Panels in the Treatment of Solid Organ Neoplasms:

Optimizing Management of Patients in Underserved and Minority Populations

 

CAZENOVIA, NY – NCODA would like to commend the Centers for Medicare and Medicaid Services (CMS) for initiating the proposed LCD DL37810 for Medicare beneficiaries with advanced solid tumors. As a patient-centered organization, we support the overall intent of LCD DL37810, which increases access to NGS technology and optimizes the management of patients with advanced solid tumors.

We would like to comment on the proposed indications and specific views documented in the Summary of Evidence listed in the proposed LCD in reference to Next Generation Sequence (NGS) Comprehensive Genomic Profile (CGP) testing. NCODA requests that the requirement:

“CGP NGS testing for patient with advanced cancer is reasonable and necessary only when more limited (i.e., individual analyte or targeted panel (5-50 genes)) testing is insufficient…”

in the “Proposed Indications” section be removed to avoid confusion regarding coverage to test for FDA approved indications. Tumor mutation burden (TMB) can only be detected using assays over 200 genes and TMB is listed as an FDA indication for eligibility of pembrolizumab for all solid tumors.

NCODA values CMS’s recognition of the benefits of RNA-based NGS. We agree with supporting both the use of RNA-based NGS and DNA-based NGS given existing technology platforms and current use of both technologies.

NCODA applauds the fact that “NGS CGP testing may especially benefit the 25% of patients with rare cancer types… and underserved minority populations with less access to tumor molecular profiling or off-label therapies.” This dedication to address cancer disparities and rare disease states by recommending NGS CGP testing to help address these populations is in desperate need. NGS CGP facilitates identification of novel uses of existing targeted therapies and/or eligibility for clinical trials with novel genetic alterations, attempting to address such populations.

At NCODA, we are patient-centered and always collaborative. We strive to provide leadership, expertise, quality standards, and forward-thinking solutions to oncology healthcare professionals across the country. While the oncology community has made progress to ensure equity in cancer care over the years, we believe the work is far from over. In addition to ensuring that all cancer patients receive quality care, NCODA believes in providing access to all regardless of status. These disparities need to be reduced and eventually eliminated. Again, we applaud CMS for initiating the proposed LCD DL37810 for Medicare beneficiaries, and we believe that this is a positive step in the right direction toward providing better care for cancer patients from underserved and/or minority populations.

# # #

 

About NCODA

NCODA is a leading nonprofit organization dedicated to empowering medically integrated oncology practices to deliver positive, patient-centered outcomes by providing leadership, expertise, quality standards, and best practices. For more information about NCODA, its Executive Council, and general updates, visit www.ncoda.org or follow @NCODAorg on Twitter.

Read More

Written by: Michelle Hoa and Natasha Heimbigner, PharmD – Summit Cancer Centers
Download Here

Description: Patients undergoing cancer treatment are more susceptible to infections due to their compromised immune system. This PQI will review which vaccinations cancer patients can or cannot use for the proper protection against preventable infections.

Background: Cancer treatments weaken the immune system rendering it more susceptible to infections.1,2 In order to prevent these infections, cancer patients can either take antimicrobial prophylaxis, get vaccinated, or avoid contact with germs.2 Generally, it is best to get vaccinated prior to the start of cancer therapy. Live vaccines should be administered at least four weeks prior to the start of chemotherapy and/or at least 3 months after completion of treatment.1,3 Inactive vaccines should be administered 2 weeks prior to the start of therapy for maximal effect, however, they can be given during therapy. Patients vaccinated during chemotherapy treatment with an inactive vaccine should consider revaccination at least 3 months after therapy as they could be rendered ineffective.3

 PQI Process:

  • Obtain patient vaccination history and reference with CDC recommendations to ensure they are current
  • Determine type of vaccination chemotherapy patient needs
    • Non-replicating (inactive) vaccines: should be given at least 2 weeks before the initiation of chemotherapy or other immunosuppressive therapy to maximize immune response1
      • Vaccination, 2 weeks prior to chemotherapy, allows for immune response against the targeted pathogen
      • Antibody response is suboptimal if given vaccination during immunosuppressive therapy but is better than not vaccinating; repeat vaccination or boosters may be beneficial in prolonging immunity1,4
    • Replicating live vaccines: should be given at least 4 weeks prior to and at least 3 months after immunosuppressive therapy1
      • Live vaccinations contain a weak live version of the virus; an immunocompromised system will not be able to fight against the pathogen (may cause vaccine-derived infections)
      • An adequate immune response usually occurs 3 to 12 months after the completion of treatment; wait at least 3 months after the completion of therapy to receive live vaccinnes5
      • Vaccination should be delayed for at least 6 months after treatment if the patient is receiving anti-B-cell antibodies2
    • Based on regimen, reference the package insert for all oncolytic specific vaccination suggestions

Patient Centered Activities:

  • If patient has not been vaccinated, counsel patient on the importance of vaccination
  • Immunocompromised patients are at higher risk for certain diseases; additional vaccines are recommended4
    • TIV and polysaccharide-based vaccines (PCV, PPV, MCV4, MPSV, and Hib vaccines)8
    • Flu vaccine:
      • Do NOT get nasal mist flu vaccine since it is a live vaccine
      • Influenza-related hospitalization is 3 to 5 times higher in cancer patients
    • Pneumococcal vaccine (PCV13 and PPV23):
      • Immunocompromised patients should receive PCV13 and are recommended to receive PPV23 vaccine about 8 weeks later;7,8 then receive a second dose of PPV23 5 years after the first PPV238
      • Patients that received at least one dose of PPV23 should receive PCV13 no sooner than 1 year after last PPV23 dose8
      • Help patients fight off serious lung, blood, or brain bacterial infections7
      • Recommended in multiple myeloma, lung cancer, chronic lymphocytic leukemia, and lymphoma1
    • Shingrix:®
      • Shingrix® is an inactivated recombinant vaccine (not recommended due to its lack of research)9
    • COVID-19 Vaccine:
      • Moderna – two doses, 4 weeks apart
      • Pfizer-BioNTech – two doses, 3 weeks apart
      • Johnson and Johnson – one dose
      • Booster – Immunocompromised patients receive a booster 4 weeks after initial immunization
    • Counsel patients who are on immunotherapy on vaccination recommendations and precautions
      • Immunotherapy has variable immunomodulatory or immunosuppressive effects
      • Vaccine may be triggering an exaggerated immune response in certain patients1
        • Reports suggest that influenza vaccines given to patients on certain types of immunotherapies triggered an amplified immune-related adverse reaction10,11
        • Some patients receiving immune checkpoint inhibitors experienced intensified immune response11
      • Consult with prescriber if vaccination is appropriate with current immunotherapy
    • Follow up with patient 3 months after chemotherapy is complete
      • If patient had inactive vaccine during treatment, remind to revaccinate 3 months post-treatment
      • If patient is over 65 or has an altered immune system, the CDC recommends a flu vaccine every year and pneumonia vaccine (PPSV23) every 5 years; PCV13 vaccine should only be given once
      • Booster Tdap vaccination should be considered for patients who have completed chemotherapy1
    • Counsel family on risk of receiving live vaccines around patients undergoing chemotherapy

References:

  1. Ariza-Heredia, Ella J, and Roy F Chemaly. “Practical Review of Immunizations in Adult Patients with Cancer.” Human Vaccines & Immunotherapeutics 11.11 (2015): 2606–2614.
  2. nccn.org/patients/resources/life_with_cancer/managing_symptoms/infections.aspx
  3. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5515a1.htm
  4. Centers for Disease Control and Prevention. Recommendations of the advisory committee on immunization practices (ACIP): Use of vaccines and immune globulins in persons with altered immunocompetence. Morbidity and Mortality Weekly Report. 1993;42(RR-4). Available from: https://dosinghealth.com/wp-content/uploads/2017/09/rr4204.pdf
  5. https://www.medscape.com/viewarticle/413557
  6. http://chemocare.com/
  7. https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/infections/vaccination-during-cancer-treatment.html
  8. https://www.pharmacytimes.com/news/cdc-committee-high-risk-adults-should-get-2-pneumococcal-vaccines
  9. https://www.cdc.gov/vaccines/vpd/shingles/hcp/shingrix/faqs.html
  10. https://www.cancernetwork.com/oncology-journal/immunizing-cancer-patients-which-patients-which-vaccines-when-give
  11. https://www.pharmaceutical-journal.com/news-and-analysis/news/influenza-vaccine-may-cause-exaggerated-immune-response-in-patients-on-cancer-immunotherapy/20202682.article?firstPass=false

Supplemental Information:

Table 1: Types of Vaccines

Type of ImmunizationPrinciple of ActionExamplesComments
Non-replicating vaccinesBased on toxoid, protein subunits, bacterial, antigens, or immunogenic proteins obtained with recombinant, technology.Tetanus, diphtheria, pertussis, poliomyelitis, hepatitis B, influenza, varicella zoster (shingles) (Shingrix®), Haemophilus influenza, pneumococcus, meningococcus, COVID-19Usually requires 3–5 doses; antibody titers diminishes with time
Replicating live vaccinesProduced by disabling the virulent properties of a disease-producing virus or bacteriumMeasles-mumps-rubella, varicella (chicken pox), varicella zoster (shingles) (Zostavax®)  intranasal influenza, yellow fever, oral polio, oral typhoidSevere reactions are possible; transmission of live pathogen may occur; most provide immunity with 1 dose
Passive immunizationAntibodies are infused to provide short-term protectionVaricella Immunoglobulin, hepatitis B immunoglobulinProtection diminishes after weeks or months

 

Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional.  This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented.  NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.
Read More

Written by: Danny Nguyen, MD, Nishan Tchekmedyian, MD, André K.D. Liem, MD, City of Hope National Medical Center

DOWNLOAD HERE 

Description: Mobocertinib (Exkivity™) is an oral EGFR tyrosine kinase inhibitor (TKI) designed to specifically target EGFR ex20ins mutations.1 This PQI will discuss effective strategies for side effect management.

Background: Mobocertinib is indicated in locally advanced or metastatic non-small cell lung cancer (NSCLC). Mobocertinib demonstrated meaningful clinical benefit in 114 platinum-pretreated patients (PPP) with EGFR ex20ins+ NSCLC in a phase 1/2 study (NCT02716116), with confirmed objective responses by independent assessment reported in 28% of patients and median duration of response of 17.5 months.2

PQI Process:  By far, the most common side effect associated with mobocertinib is diarrhea (92%), followed by rash (78%), stomatitis (46%), vomiting (40%) and nausea (37%). Mobocertinib also includes a boxed warning for QTc prolongation and Torsades de Pointes. Below are tips that may improve patient quality of life on mobocertinib thereby maximizing the benefit patients may receive from mobocertinib:

  • Monitoring:4
    • Monitor QTc and electrolytes at baseline and periodically during treatment
    • Monitor for new or worsening pulmonary symptoms indicative of Interstitial Lung Disease (ILD)/pneumonitis and immediately withhold in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed
    • Monitor cardiac function, including left ventricular ejection fraction, at baseline and during treatment. Withhold, then resume at reduced dose or permanently discontinue based on severity
    • Monitor electrolytes and advise patients to start an antidiarrheal agent at first episode of diarrhea and to increase fluid and electrolyte intake. Withhold, reduce, or permanently discontinue based on severity
  • Drug-Drug Interactions: 4
    • Mobocertinib is a CYP3A substrate
      • Avoid concomitant use of mobocertinib with strong or moderate CYP3A inhibitor. If concomitant use is unavoidable, reduce the dose and monitor the QTc interval more frequently with ECGs
      • Avoid concomitant use with strong/moderate CYP3A inducers, may reduce anti-tumor activity
      • Avoid concomitant use of hormonal contraceptives
      • Avoid concomitant use of other medications known to prolong the QTc interval. If concomitant use is unavoidable, monitor the QTc interval more frequently with ECGs
Diarrhea Severity (CTCAE Grade)Intervention
Grade 0 or on Cycle 1, Day 1Consider prophylaxis when prescribing mobocertinib:

a) Loperamide 2 mg PO daily to BID (titrate to 1-2 BM per day)

Grade 1Loperamide 4 mg, followed by 2 mg after each loose stool (max: 16 mg/day)
Grade 2Interventions listed in Grade 1 and:

a) Diphenoxylate/atropine 5 mg QID until control achieved (max: 20 mg/day)

b) Consider cholestyramine 4 g orally BID (30 minute prior to meals)

c)  Consider budesonide 9 mg daily for 4 weeks

d) Assess the need for IV hydration (saline) frequently

Grade 3Interventions listed in Grade 1 and 2 and:

a) Consider holding mobocertinib until resolution of diarrhea to Grade ≤ 1

b) Opium tincture (morphine 10 mg/mL) 6 mg of undiluted opium tincture QID

c)  Octreotide 100 to 150 mcg sq TID

d) Strongly consider IV hydration unless contraindicated

Rash Severity
(CTCAE Grade)
Intervention
Grade 0 or on Cycle 1, Day 1Consider prophylaxis with:

a) Doxycycline 100 mg PO BID or Minocycline 100 mg PO BID

b) Daily moisturizing lotion, bland emollient

Grade 1Interventions listed in Grade 0 and:

a) Face: hydrocortisone 1.0% to 2.5% BID to affected area

Body: triamcinolone 0.1% BID to affected area

b) Derma-Smoothe* 0.01% (or similar) apply topical TID to affected area copiously

Grade 2Interventions listed in Grade 0 and 1 and:

a)     Add clindamycin 1.0% cream BID to affected area

Grade 3Interventions listed in Grade 0 and:

a) Hold mobocertinib until resolution of rash to Grade ≤ 1

b) Increase clindamycin 1.0% to 2.0% cream BID to affected area

c)  Start on oral prednisone 5 to 10 mg PO daily.  Increase by 5 to 10 mg PO weekly depending on improvement.  Alternatively, can start on a Medrol DosePak

Grade 4Interventions listed in Grade 3

*Special consideration for folliculitis/rash involving the scalp

 

Stomatitis Severity
(CTCAE Grade)
Intervention
Grade 0 or on Cycle 1, Day 1Consider prophylaxis with:

a) Dexamethasone 0.5 mg/5mL oral solution: 10 mL swish and spit QID 1 hour NPO afterwards

b) Biotѐne mouthwash

c)  Doxycycline 100 mg PO BID or minocycline 100 mg PO BID

Grade 1Interventions listed in Grade 0
Grade 2Interventions listed in Grade 0 and:

a) Magic mouthwash1

Grade 3Interventions listed in Grade 2 and:

a) Hold mobocertinib until resolution of mucositis to Grade ≤ 1

b) Start on oral prednisone 5 to 10 mg PO daily.  Increase by 5 to 10 mg PO weekly depending on improvement.  Alternatively, can start on a Medrol DosePak

 

Patient Centered Activities:3

  • Provide Oral Chemotherapy Education (OCE) Sheet
  • Provide Treatment Support Kit
  • Counsel patient on how to take mobocertinib and the common side effects
  • Some patients may find that certain foods or may worsen symptoms and should be avoided
  • Patients should be encouraged to maintain hydration, especially if they are experiencing diarrhea
  • Taking mobocertinib at different times in the day may improve symptoms. Instituting a brief dose hold on mobocertinib may be required to improve symptoms, but should be minimized as they may impact overall effectiveness of mobocertinib3 

References:

  1. Riely GJ, Neal JW, Camidge DR, et al. Activity and safety of mobocertinib (TAK-788) in previously treated non–small cell lung cancer with EGFR exon 20 insertion mutations from a phase 1/2 trial. Cancer Discov. 2021;11(7):1688-1699.
  2. Zhou C, Ramalingam SS, Kim TM, et al. Mobocertinib in platinum-pretreated patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer: phase 1/2 open-label study. JAMA Oncol. 2021. In press.
  3. Nguyen D,Ramalingam SS, Spira AI, et al. (2021, Oct). Characterization of GI Toxicities and Their Impact on Efficacy in Patients With EGFR Exon 20 Insertion+ (ex20ins+) Non–Small Cell Lung Cancer (NSCLC) Treated With Mobocertinib (TAK-788) Who Previously Received Platinum Chemotherapy. European Society for Medical Oncology (Virtual).
  4. EXKIVITY (mobocertinib) [prescribing information]. Lexington, MA: Takeda Pharmaceuticals America.
Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional.  This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented.  NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.
Read More