Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Optimizing the Management of Advanced Cervical Cancer With Checkpoint Inhibitor Therapy

753 views

Published on

i3 Health is pleased to make the clinician's resource guide available for use as a nonaccredited self-study or teaching resource.

Published in: Education
  • Be the first to comment

  • Be the first to like this

Optimizing the Management of Advanced Cervical Cancer With Checkpoint Inhibitor Therapy

  1. 1. www.i3Health.com Clinical Tools and Resources for Self-Study and Patient Education ADVANCED CERVICAL CANCER REFERENCE GUIDE The clinical tools and resources contained herein are provided as educational adjuncts to the CME/CE-certified online activity Optimizing the Management of Advanced Cervical Cancer With Checkpoint Inhibitor Therapy. To access the activity and earn CME/CE credit, visit: https://www.i3Health.com/Cervical-Cancer CONTENTS I: General Staging of Cervical Tumors............................................................................. 2 II: FIGO and TNM Staging of Cervical Tumors................................................................ 3 III: Immune Checkpoint Inhibitors: Overview................................................................... 5 IV: Immune-Related Adverse Events: Overview .............................................................. 5 V: Management of Common Immune-Related Adverse Events: ESMO Guidelines ....... 6 VI: Management of Skin Rash/Toxicity: ESMO Guidelines............................................ 10 VII: Management of Dermatologic Immune-Related Adverse Events: ASCO Guidelines11 VIII: Patient Education On Immune-Related Adverse Events ........................................ 13
  2. 2. 082ACC Reference Guide | Page 2 of 13 www.i3Health.com I: GENERAL STAGING OF CERVICAL TUMORS Staging 0 Carcinoma in Situ The first stage of cervical cancer is carcinoma in situ (also known as precancer or severe dysplasia), in which a group of abnormal cells has started to grow but has not yet spread to nearby tissues. Because stage 0 “precancers” are likely to eventually spread deeper into the tissue and become cancerous, they should be treated I-IIA Early Cervical Cancer Although more extensive than stage 0, these cancers are still limited to the cervix IIB-IVA Advanced Cervical Cancer Cervical cancer that has spread beyond the cervix and invaded the surrounding pelvic tissues in the vagina, rectum, or bladder is known as locally advanced cervical cancer IVB Recurrent Cervical Cancer Cervical cancer that has spread beyond the pelvis (into the lungs or liver, for example), or has returned following initial therapy, is placed in this category Memorial Sloan Kettering Cancer Center (2018). Cervical cancer diagnosis. Available at: https://www.mskcc.org
  3. 3. 082ACC Reference Guide | Page 3 of 13 www.i3Health.com II: FIGO AND TNM STAGING OF CERVICAL TUMORS Staging of cervical tumors is by the Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) and TNM (tumor, node, metastasis) classifications (Union for International Cancer Control) TNM Clinical Classifications TNM Stage FIGO Stage Definition T: Primary Tumor TX — Primary tumor cannot be assessed T0 — No evidence of primary tumor Tis — Carcinoma in situ (preinvasive carcinoma) T1 I Tumor confined to the cervixa T1 T1ab,c IA Invasive carcinoma diagnosed only by microscopy. Stromal invasion with a depth ≤5.0 mm measured from the base of the epithelium and a horizontal spread ≤7.0 mm T1a1 IA1 Measured stromal invasion ≤3.0 mm in depth and ≤7.0 mm in horizontal spread T1a2 IA2 Measured stromal invasion >3.0 mm and ≤5.0 mm in depth with a horizontal spread ≤7.0 mmd T1b IB Clinically visible lesion confined to the cervix or microscopic lesion greater than T1a/IA2 T1b1 IB1 Clinically visible lesion ≤4.0 cm in greatest dimension T1b2 IB2 Clinically visible lesion >4.0 cm in greatest dimension T2 II Tumor invades beyond uterus but not to pelvic wall or lower third of vagina T2 T2a IIA Tumor without parametrial invasion T2a1 IIA1 Clinically visible lesion ≤4.0 cm in greatest dimension T2a2 IIA2 Clinically visible lesion >4.0 cm in greatest dimension T2b IIB Tumor with parametrial invasion
  4. 4. 082ACC Reference Guide | Page 4 of 13 www.i3Health.com TNM Clinical Classifications (Cont.) TNM Stage FIGO Stage Definition T3 III Tumor involves lower third of vagina, extends to pelvic wall, or causes hydronephrosis or non-functioning kidney T3 T3a III Tumor involves lower third of vagina T3b IIIB Tumor extends to pelvic wall or causes hydronephrosis or non- functioning kidney T4 IVA Tumor invades mucosa of the bladder or rectum or extends beyond true pelvise N: Regional Lymph Nodesf NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis M: Distant Metastasisf M0 No distant metastasis M1 Distant metastasis (includes inguinal lymph nodes and intraperitoneal disease; excludes metastasis to vagina, pelvic serosa, or adnexa) a: Extension to corpus uteri should be disregarded b: The depth of invasion should be taken from the base of the epithelium, either surface or glandular, from which it originates. The depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the most superficial adjacent papillae to the deepest point of invasion. Vascular space involvement, venous or lymphatic, does not affect classification c: All macroscopically visible lesions even with superficial invasion are T1b/IB d: Vascular space involvement, venous or lymphatic, does not affect classification e: Bullous edema is not sufficient to classify a tumor as T4 f: No FIGO equivalent Marth C, Landoni F, Mahner S, et al (2017). Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Available at: https://www.esmo.org
  5. 5. 082ACC Reference Guide | Page 5 of 13 www.i3Health.com III: IMMUNE CHECKPOINT INHIBITORS: OVERVIEW Drug Type Examples CTLA-4 inhibitors Ipilimumab (Yervoy® ) PD-1 inhibitors Nivolumab (Opdivo® ) Pembrolizumab (Keytruda® ) PD-L1 inhibitors Atezolizumab (Tecentriq® ) Avelumab (Bavencio® ) Durvalumab (Imfinzi® ) Combination therapy Ipilimumab + nivolumab American Cancer Society (2018). Immune checkpoint inhibitors to treat cancer. Available at: https://www.cancer.org IV: IMMUNE-RELATED ADVERSE EVENTS: OVERVIEW Affected Organ(s) AE CTLA-4 Inhibitors PD-1/PD-L1 Inhibitors Skin Rash 24% 15% Itching 25% – 35% 13% – 20% GI tract Diarrhea 27% – 54% Very Low Colitis 8% – 22% Lungs Cough/ breathlessness Very low 20% – 40% Pneumonitis 2% – 4% Liver Hepatic toxicity 5% – 10% 5% – 10% Endocrine System Thyroid effects 1% – 5% 5% – 10% Hypophysitis 1% Very rare Haanen J, Jordan K, Longo F, et al (2017). Immunotherapy-related side effects and their management: an ESMO guide for patients. Available at: https://www.esmo.org
  6. 6. 082ACC Reference Guide | Page 6 of 13 www.i3Health.com V: MANAGEMENT OF COMMON IMMUNE-RELATED ADVERSE EVENTS: ESMO GUIDELINES Skin Side Effects (Rash/Itching) Grade Symptoms Management 1 Rash covering <10% of body surface area (BSA) with or without symptoms Topical moisturizing cream or ointment, oral or topical antihistamines for itching (if present) and/or topical corticosteroid cream (mild strength); continue checkpoint inhibitor treatment 2 Rash covering 10% to 30% BSA with or without symptoms Topical moisturizing cream or ointment, oral or topical antihistamines for itching (if present) and/or topical corticosteroid cream (medium strength); continue checkpoint inhibitor treatment Self-help measures for grade 1/2 (mild to moderate) symptoms: avoid contact with skin irritants and exposure to sun 3 Rash covering <30% BSA with or without symptoms Topical moisturizing cream or ointment, oral or topical antihistamines for itching (if present) and/or topical corticosteroid cream (medium strength); continue checkpoint inhibitor treatment 4 Rash covering 30% BSA with infection or other complications Intravenous corticosteroids and urgent specialist review; permanently discontinue checkpoint inhibitor therapy European Society for Medical Oncology (2017). Patient guide on immunotherapy-related side effects and their management. Available at: https://www.esmo.org
  7. 7. 082ACC Reference Guide | Page 7 of 13 www.i3Health.com Gastrointestinal Side Effects (Diarrhea/Colitis) Grade Symptoms Management 1 Increase of <3 liquid stools per day since commencing treatment; feeling well Anti-diarrheal medication (eg, loperamide) and oral electrolyte supplementation if required; continue checkpoint inhibitor treatment 2 Increase of 4 to 6 liquid stools per day since commencing treatment; abdominal pain, blood in stool, nausea, or night-time symptoms Oral corticosteroids and further tests (eg, sigmoidoscopy/colonoscopy); withhold checkpoint inhibitor treatment until symptoms resolve Self-help measures for grade 1/2 (mild to moderate) diarrhea/colitis: drink plenty of fluids, avoid high-fiber/lactose diet 3 Increase of >6 liquid stools per day since commencing treatment or symptoms occurring within 1 hour of eating; also applies to patients to patients with grade 1/2 stool frequency who have other symptoms such as dehydration, fever, or rapid heart rate Hospital admission, intravenous corticosteroids, and further tests (eg, sigmoidoscopy/colonoscopy) if not already done; if there is no response to corticosteroids, strong immunosuppressive drugs (eg, infliximab) can be used. Permanently discontinue checkpoint inhibitor therapy 4 European Society for Medical Oncology (2017). Patient guide on immunotherapy-related side effects and their management. Available at: https://www.esmo.org Lung Side Effects (Pneumonitis) Grade Symptoms Management 1 None, based on findings from X-ray examination Monitor every 2 to 3 days and test to rule out other causes; may delay checkpoint inhibitor treatment 2 Breathlessness, cough, chest pain Antibiotics if infection suspected, oral corticosteroids if no improvement on antibiotics or no infection found, further tests including CT scan and bronchoscopy; withhold checkpoint inhibitor treatment 3/4 Worsening symptoms, difficulty breathing Hospital admission, intravenous corticosteroids, other stronger immunosuppressive drugs if no improvement; permanently discontinue checkpoint inhibitor treatment
  8. 8. 082ACC Reference Guide | Page 8 of 13 www.i3Health.com Liver Side Effects (Hepatitis) Grade Symptoms Management 1 None, based on laboratory values from blood tests of liver enzyme levels No immediate treatment necessary; repeat blood tests in one week’s time; continue checkpoint inhibitor treatment 2 Repeat blood tests repeated every 3 days; further liver function tests with oral corticosteroid treatment if liver enzyme levels are rising; withhold checkpoint inhibitor treatment but may restart if symptoms improve after corticosteroids have been gradually reduced 3 Tiredness, feeling unwell, mild joint or muscle pains, decreased appetite or weight loss, nausea, itching, rash, diarrhea, bloating; may have few or even no symptoms Oral/intravenous corticosteroids, depending on liver enzyme levels; discontinue checkpoint inhibitor treatment 4 Hospital admission, intravenous corticosteroids, and specialist review; permanently discontinue checkpoint inhibitor treatment European Society for Medical Oncology (2017). Patient guide on immunotherapy-related side effects and their management. Available at: https://www.esmo.org
  9. 9. 082ACC Reference Guide | Page 9 of 13 www.i3Health.com Endocrine Side Effects Condition Symptoms Management Hyperthyroidism Usually transient and grade 1/2; may be no symptoms if mild. Various symptoms with increasing severity, including nervousness, anxiety, irritability, mood swings, difficulty sleeping, persistent tiredness and weakness, sensitivity to heat, swelling in the neck from enlarged thyroid gland, irregular and/or unusually fast heart rate (palpitations), twitching or trembling, weight loss If symptomatic, initiate treatment with beta- blockers; interrupt checkpoint inhibitor therapy until symptoms resolve. Regular blood tests to monitor thyroid hormone levels Hypothyroidism Usually grade 1/2; may be no symptoms if mild. Various symptoms with increasing severity, including tiredness, sensitivity to cold, weight gain, constipation, depression, slow movements and thoughts, muscle aches and weakness, muscle cramps, dry and scaly skin, brittle hair and nails Treat with long-term hormone replacement therapy (with thyroid hormones, depending on severity) and oral corticosteroids if thyroid gland is inflamed; can interrupt checkpoint inhibitor therapy until symptoms resolve. Regular blood tests to monitor thyroid hormone levels Hypophysitis Usually grade 1/2; no symptoms if mild. Various symptoms with increasing severity, including headache, double vision, excessive thirst, large volumes of dilute urine, various hormonal imbalances and related symptoms Oral/intravenous corticosteroids and appropriate hormone replacement therapy (depending on severity and which set of hormones is affected); continue checkpoint inhibitor therapy during less severe (most) symptoms, but may withhold for more severe symptoms European Society for Medical Oncology (2017). Patient guide on immunotherapy-related side effects and their management. Available at: https://www.esmo.org
  10. 10. 082ACC Reference Guide | Page 10 of 13 www.i3Health.com VI: MANAGEMENT OF SKIN RASH/TOXICITY: ESMO GUIDELINES Haanen JBAG, Carbonnel F, Robert C, et al (2017). Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 28(suppl_4):iv119-iv142. DOI:10.1093/annonc/mdx225
  11. 11. 082ACC Reference Guide | Page 11 of 13 www.i3Health.com VII: MANAGEMENT OF DERMATOLOGIC IMMUNE-RELATED ADVERSE EVENTS: ASCO GUIDELINES Rash/Inflammatory Dermatitis Definition Erythema multiforme minor is a targetoid reaction in the skin and mucous membranes that is usually triggered by infections, such as herpes simplex viruses, but can also be associated with an immune-related drug eruption. If erythema multiforme minor progresses to erythema multiforme major, it can be a harbinger of the following types of eruptions: • SCAR (severe cutaneous adverse reactions, such as SJS) • Lichenoid (lesions resembling the flat-topped, polygonal, and sometimes scaly or hypertrophic lesions of lichen-planus) • Eczematous (inflammatory dermatitis characterized by pruritic, erythematous, scale, or crusted papules or plaques on the skin; vulnerable to superinfection) • Psoriasiform (dermatitis resembling the well-demarcated, erythematous, and scaly papules and plaques of psoriasis) • Morbilliform (a nonpustular, nonbullous measles-like exanthematous rash of skin often referred to as “maculopapular;” lacks systemic symptoms or laboratory abnormalities, excluding occasional isolated peripheral eosinophilia) • Palmoplantar erythrodysesthesia (hand-foot syndrome: redness, numbness, burning, itching, and superficial desquamation of the palms and soles) • Neutrophilic dermatoses (eg, Sweet syndrome) • Others Diagnostic Workup • Pertinent history and physical examination • Rule out any other etiology, such as infection, effect of another drug (for photosensitivity, review full list of patient medications to eliminate other drug-induced causes), or a skin condition linked to another systemic disease or unrelated primary skin disorder • Biologic checkup if needed, including blood cell count and liver and kidney tests • Directed serologic studies if an autoimmune condition such as lupus or dermatomyositis is suspected (screening antinuclear antibody test, SS-A/Anti-Ro, SS-B/Anti-La if predominantly photodistributed/photosensitivity, antihistone, double-stranded DNA, and other relevant serologies). Consider expanding serologic studies or diagnostic workup if other autoimmune conditions are considered based on signs and symptoms • Skin biopsy • Consider clinical monitoring with use of serial clinical photography Adapted from: Brahmer JR, Lacchetti C, Schneider BJ, et al (2017). Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol, 36(17):1714-1768. DOI:10.1200/JCO.2017.77.6385
  12. 12. 082ACC Reference Guide | Page 12 of 13 www.i3Health.com Rash/Inflammatory Dermatitis (Cont.) Grade Symptoms Management Grading according to CTCAE is a challenge for skin. Instead, severity may be based on BSA, tolerability, morbidity, and duration. 1 Symptoms do not affect quality of life or are controlled with topical regimen and/or oral antipruritic • Continue ICPi • Treat with topical emollients and/or topical corticosteroids of mild to moderate potency • Counsel patients to avoid skin irritants and sun exposure 2 Inflammatory reaction that affects quality of life and requires intervention based on diagnosis • Consider holding ICPi and monitor weekly for improvement. If not resolved, interrupt treatment until skin AE has reverted to grade 1 • Consider initiating prednisone 1 mg/kg or equivalent, tapering over at least 4 weeks • In addition, treat with topical emollients, oral antihistamines, and medium- to high- potency topical corticosteroids 3 Similar to grade 2 but with failure to respond to indicated interventions for grade 2 dermatitis • Hold ICPi therapy; consult with dermatologist to determine appropriateness of resuming • Treat with topical emollients, oral antihistamines, and high- potency topical corticosteroids • Initiate (methyl)prednisolone 1-2 mg/kg or equivalent, tapering over at least 4 weeks 4 All severe rashes (intolerable and unmanageable after prior interventions) • Immediately hold ICPi; consult with dermatologist to determine appropriateness of resuming ICPi therapy upon resolution of skin toxicity and once corticosteroids are reduced to prednisone ≤10 mg or equivalent • Systemic corticosteroids: IV (methyl)prednisolone 1-2 mg/kg or equivalent with slow tapering when the toxicity resolves • Monitor closely for progression to severe cutaneous adverse reaction • Admit patient immediately with direct oncologist involvement and an urgent dermatology consult • Consider alternative antineoplastic therapy ahead of resuming ICPis if the skin irAE does not resolve to grade 1 or less; if ICPis are the patient’s only option, consider restarting once these adverse effects have resolved to a grade 1 level Adapted from: Brahmer JR, Lacchetti C, Schneider BJ, et al (2017). Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol, 36(17):1714-1768. DOI:10.1200/JCO.2017.77.6385
  13. 13. 082ACC Reference Guide | Page 13 of 13 www.i3Health.com VIII: PATIENT EDUCATION ON IMMUNE-RELATED ADVERSE EVENTS Courtesy of: European Society for Medical Oncology (2017). Patient guide on immunotherapy-related side effects and their management. Available at: https://www.esmo.org

×