EGFR-TARGETED THERAPIES FOR ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) Pocket Guide

Transcription

1 EGFR-TARGETED THERAPIES FOR ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) Pocket Guide The information in this pocket guide is intended as reference material and should not replace clinical judgment or updated recommendations that may supersede those provided here.

2 Molecular Testing in NSCLC The NCCN NSCLC Guidelines Panel strongly endorses broader molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available, or to appropriately counsel patients regarding the availability of clinical trials. Broad molecular profiling is a key component of the improvement of care of patients with NSCLC. National Comprehensive Cancer Network 1 In the setting of lung cancer resection specimens, EGFR and ALK testing is recommended for adenocarcinomas and mixed lung cancers with an adenocarcinoma component, regardless of histologic grade and patients should not be excluded from testing on the basis of clinical characteristics. CAP/IASLC/AMP 2 NSCLC MUTATIONS - Adenocarcinoma Histology 3 Liquid Biopsy Cells release small fragments of cell-free plasma DNA (cfdna) into circulation by multiple mechanisms such as secretion, apoptosis, and necrosis. 4 cfdna includes normal and circulating tumor DNA (ctdna) -Half-life = ~2 hours In June of 2016, the US Food and Drug Administration approved the first liquid biopsy EGFR mutation diagnostic test. 5 1 National Comprehensive Cancer Network. Available at: 2 Leighl NB, et al. J Clin Oncol. 2014; 3 Adapted from Chia PL, et al. Clin Epidemiol. 2014; 4 Diaz Jr. L, et al. J Clin Oncol. 2014; 5 FDA. Available at: ucm htm.

3 EGFR TKI Targeted Therapies Erlotinib, gefitinib, and afatinib are all indicated for first-line therapy in EGFR sensitizing mutations. Osimertinib received accelerated approval from the FDA in It is indicated in T790M EGFR mutation-positive NSCLC. Sensitizing EGFR mutation positive EGFR mutation discovered prior to first line chemotherapy EGFR mutation discovered during first line chemotherapy FIRST LINE THERAPY Erlotinib (category 1) or Afatinib (category 1) or Gefitinib (category 1) *If tissue biopsy is not feasible, plasma biopsy should be considered. Consider reflex to tissue based testing, if plasma test is negative for the T790M mutation. NOTE: All recommendations are category 2A unless otherwise indicated Asymptomatic T790M testing if Complete progression* planned chemotherapy, including maintenance Symptomatic therapy, or interrupt, followed by erlotinib or afatinib or gefitinib Brain Systemic Isolated lesion Multiple lesions SUBSEQUENT THERAPY Consider local therapy Osimertinib (if T790M+) (category 1) OR Continue erlotinib or afatinib or gefitinib Consider local therapy Osimertinib (if T790M+) (category 1) OR Continue erlotinib or afatinib or gefitinib Consider local therapy Continue erlotinib or afatinib or gefitinib OR T790M+ T790M Progression Osimertinib (category 1), if not previously given See first line therapy options for adenocarcinoma and squamous cell carcinoma or PD L1 expression positive (>50%), see first line therapy Adapted from the National Comprehensive Cancer Network. Available at:

4 TOXICITIES OF EGFR TKI THERAPY All Grade Adverse Events EGFR TKI Toxicities Percentage of Patients Experiencing (%) Afatinib Erlotinib =Not Reported Compiled from FDA Prescribing Information; current as of September 2016.

5 TOXICITIES OF EGFR TKI THERAPY All Grade Adverse Events EGFR TKI Toxicities Percentage of Patients Experiencing (%) Gefitinib Osimertinib =Not Reported Compiled from FDA Prescribing Information; current as of September 2016.

6 TOXICITIES OF EGFR TKI THERAPY Grade 3 Adverse Events EGFR TKI Toxicities Percentage of Patients Experiencing (%) Afatinib Erlotinib 8 <1 0 <1 < =Not Reported Compiled from FDA Prescribing Information; current as of September 2016.

7 TOXICITIES OF EGFR TKI THERAPY Grade 3 Adverse Events EGFR TKI Toxicities 30 Gefitinib Osimertinib Percentage of Patients Experiencing (%) =Not Reported Compiled from FDA Prescribing Information; current as of September 2016.

8 MASCC RASH GRADING SCALE EGFR Toxicity Management Papulopustular eruption (Grading individually for face, scalp, chest, or back) Grade 1 Grade 2 Grade 3 1A: Papules or pustules <5 OR 1 area of erythema or edema <1 cm in size 1B: Papules or pustules <5 OR 1 area of erythema or edema <1 cm in size AND pain or pruritus 2A: Papules or pustules 6-20 OR 2 5 areas of erythema or edema <1 cm in size 2B: Papules or pustules 6-20 OR 2 5 areas of erythema or edema <1 cm in size AND pain, pruritus or effect on emotions or functioning 3A: Papules or pustules >20 OR >5 areas of erythema or edema <1 cm in size 3B: Papules or pustules >20 OR >5 areas of erythema or edema <1 cm in size AND pain or pruritus or effect on emotions or functioning MASCC = Multinational Association of Supportive Care in Cancer Adapted from Lacouture ME, et al. Support Care Cancer

9 EGFR Toxicity Management MASCC RASH PREVENTION AND TREATMENT GUIDELINES Preventive Topical Systemic Treatment Topical Systemic Recommended Hydrocortisone 1% cream with moisturizer and sunscreen BID Minocycline 100 mg daily Doxycyline 100 mg BID Alclometasone 0.05% cream Fluocinonide 0.05% cream BID Clindamycin 1% Doxycycline 100 mg BID Minocycline 100 mg daily Isotretinoin at low doses (20-30 mg/d) Not Recommended Pimecrolimus 1% cream Tazarotene 0.05% cream Sunscreen as single agent a EGFR inhibitor study MASCC = Multinational Association of Supportive Care in Cancer BID = twice daily Adapted from Lacouture ME, et al. Support Care Cancer Level of Evidence II a Recommendation Grades Tetracycline 550 mg BID II a A Vitamin K1 Cream IV a C Acitretin IV a C C Comments Doxycycline is preferred in patients with renal impairment. Minocycline is less photosensitizing. Fluocinonide 0.05% cream BID should not be used on the face for more than 2 weeks at a time. Isotretinoin is photosensitizing and can cause xerosis. Monitor lipids and liver enzymes with retinoids. Lacouture ME, et al. Support Care Cancer

10 NCI-CTCAE GRADING SCALE EGFR Toxicity Management Diarrhea Grade 1 Grade 2 Grade 3 Grade 4 Increase of <4 stools per day over baseline Increase of 4 6 stools per day over baseline Increase of >7 stools per day over baseline Incontinence Hospitalization indicated Limits self care activities of daily living Lifethreatening consequences Urgent intervention needed Adapted from National Cancer Institute. Available at:

11 DIARRHEA MANAGEMENT Grade 1 Grade 2 Grade 3 & 4 Stop laxatives. Drink 8 10 glasses of clear fluids daily. Immediately start loperamide: 4 mg (2 tablets) followed by 2 mg (1 tablet) after each loose stool (up to 20 mg daily) until bowel movements cease for 12 hours. Maintain dose level of EGFR TKI. EGFR Toxicity Management Continue loperamide. Assess for dehydration and electrolyte imbalance. Consider intravenous fluids and electrolyte replacement. If diarrhea does not improve after 48 hours, temporarily discontinue EGFR TKI. Upon improvement to grade 1, restart at a reduced dose (except gefitinib, which should be restarted at the original dose). Plus: Use stool cultures to rule out an infectious process. Apply aggressive intravenous fluid replacement for 24 hours or more. Use hospitalization to monitor the patient s progress. Consider prophylactic antibiotics if the patient is also neutropenic. Temporarily discontinue EGFR TKI. Upon improvement to grade 1, restart at a reduced dose (except gefitinib, which should be restarted at the original dose). Permanently discontinue EGFR TKI if diarrhea does not return to grade 1 within 14 days despite treatment discontinuation and best supportive care. Adapted from Hirsh V, et al. Curr Oncol

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