Contemporary Nursing Management of EGFR Inhibitor Rash
Evolving Nursing Management Strategies in the Era of Tumor Histology and Biomarker-Driven Treatment Selection for Advanced NSCLCBeth Eaby-Sandy, MSN, CRNP, OCNNurse PractitionerAbramson Cancer Center
Disclosure of Conflicts of InterestBeth Eaby-Sandy, MSN, CRNP, OCN discloses the following relationships:Clovis (advisory board)Astra Zeneca (advisory board)Amgen (speakers bureau)Merck (speakers bureau)Eisai (speakers bureau)Celgene (speakers bureau)
Learning Objectives
Explain the role of tumor histology and molecular biomarkers in treatment planning for advanced NSCLCDistinguish novel NSCLC therapies available for first-line therapy, maintenance therapy, and the treatment of elderly patientsApply NSCLC supportive care plans based on shared goal setting, patient health status, periodic clinical assessment, and symptom management
NSCLC = non-small cell lung cancer.
NSCLC: Scope of the Problem
Prostate: 220,800 (26%)Lung/Bronchus: 115,610 (13%)Colon/Rectum: 69,090 (8%)Breast: 231,840 (29%)Lung/Bronchus: 105,590 (13%)Colon/Rectum: 63,610 (8%)
ACS, 2015.Estimated New Cancer Cases in 2015
NSCLC: Scope of the Problem
Prostate: 27,540 (9%)Lung/Bronchus: 86,380 (28%)Colon/Rectum: 26,100 (8%)Breast: 40,290 (15%)Lung/Bronchus: 71,660 (26%)Colon/Rectum: 23,600 (9%)
ACS, 2015.Estimated New Cancer Deaths in 2015
PERSPECTIVE (Deaths)Lung/Bronchus = 158,040 (27%)Breast + Prostate + Colon/Rectum = 117,970 (20%)
Lung Cancer Stages and SurvivalNCI, 2015.
Only 16% of lung cancers are diagnosed at a localized stage, which is associated with a 5-year survival rate of 54.8%. Most patients (57%) present with advanced disease, which is associated with a 5-year survival rate of 4.2% (NCI, 2015).
Understanding the Histology of Lung CancerNon-small cell lung cancer83% of lung cancersAbout 10-15% of cases arenever smokers
Small cell lung cancer13% of lung cancersVery aggressive type99% of cases associated with smoking
ACS, 2015.
Based on pathologic features, lung cancers are classified as non-small cell lung cancer, which accounts for 83% of cases, or small cell lung cancer, which accounts for 13% of cases (ACS, 2015).
NSCLC: Breakdown by Subtype Adenocarcinoma (44%)Most common type of NSCLCMost common type innonsmokers Large cell carcinoma (3%) Other (23%) Squamous (26%)Usually more centralizedMore frequently associated with significant cough and hemoptysis
Houston et al, 2014.
NSCLC is divided into three major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma.
NSCLC: Why Does Histology Matter?In past, all NSCLC patients were treated the sameData have shown that the use of certain agents in certain histologies results in improved survival and response ratesHistology may predict the presence of biomarkersSafety parameters of certain treatments depend on histologyNCCN, 2015b.
Clinical trial data support the importance of differentiating between squamous and nonsquamous histologies in treatment selection and supportive care planning (NCCN, 2015b).
NSCLC: Molecular BiomarkersMost commonly found in adenocarcinoma, rare in squamous cell carcinomaConsider testing in squamous cell for never smokers or in mixed adenocarcinoma and squamousThree most common mutations in NSCLC:KRAS mutationEGFR mutationEML4-ALK gene translocationEGFR and EML4-ALK most common in patients with never/minimal smoking history
Hirsch, 2012; NCCN, 2015b.
Molecular biomarkers and gene profiles have been correlated with histologic subtype (Hirsch, 2012).
NSCLC: Breakdown of Biomarkers
Hirsch, 2012.1%
The three most common molecular biomarkers found in NSCLC are KRAS mutations, EGFR mutations, and EML4-ALK gene translocations (Hirsch, 2012).
NCCN, 2015b; Langer et al, 2010.EGFRTransmembrane receptorDetectable in about 80-85% of patientsLevel of expression varies widelyMutations in this domain (10-15% of pts) result in activation of the tyrosine kinase domain with significantly better response to erlotinib or gefitinib or afatinibMutations: highest incidence in never smokers, adenocarcinoma, women, and patients with Asian ethnicityKRAS 25% of North American population Associated with smoking and resistance to tyrosine kinase inhibitors (TKIs) There are different types of KRAS mutations Therapy with drugs other than erlotinib should be considered first EML4-ALK Incidence of EML4-ALK translocation: 2-7%Estimated prevalence of EML4-ALK in lung cancer: 6,000 pts/yr US; up to 40,000 pts/yr globallyMost EML4-ALK fusion events observed in lung adenocarcinoma specimens vs. squamous or small cell histologiesEML4-ALK almost never coexists with EGFR, HER2, or KRAS mutations, indicating it is a distinct disease subtype
Molecular Abnormalities in NSCLC With Current Implications
The treatment of patients with NSCLC is evolving toward a more personalized approach that utilizes specific molecular and genetic tumor profiles in treatment planning (NCCN, 2015b).
Molecular Abnormalities of InterestROS 1 rearrangement1-2% of NSCLCDetected via FISH testSensitive to crizotinibUsually in younger, never smokersT790M EGFR resistance mutation>60% of patients develop it after treatmentDrugs in clinical trials: CO-1686, AZD9291BRAF4% NSCLCMost common is V600EDecreased PFS from platinum-based chemotherapyDrugs in clinical trials: dabrafenibRET1-2% NSCLCHighly associated with young, never smokersDrugs in clinical trials: vandetanib, cabozantinib
FISH = fluorescence in situ hybridization; PFS = progression-free survival.Bergethon et al, 2012; Cardarella et al, 2013; Tsuta et al, 2014.
Why Do Biomarkers Matter?PFS with standard chemotherapy regimens in NSCLC:Pemetrexed/cisplatin: 5 monthsPaclitaxel/carboplatin/bevacizumab: 6 monthsPFS with EGFR mutated NSCLC receiving EGFR targeted therapy:Gefitinib: 9.5 monthsErlotinib: 9.7 monthsAfatinib: 11.0 monthsPFS with ALK-positive NSCLC receiving ALK inhibitor:Crizotinib: 9.7 monthsCamidge et al, 2012; Yang Shih, et al, 2012; Rosell et al, 2012; Fukuoka et al, 2011; Scagliotti et al, 2008; Sandler et al, 2006.
Studies have shown that the use of certain novel therapies in certain histologies results in improved survival rates.
Patient Factors in Treatment PlanningPatient ECOG PSPS is a predictor of survival/tolerating chemotherapyPS 0-1 patients tolerate chemotherapy bestPS 2 patients can potentially benefit, even from doublet chemotherapy; however, toxicity must be monitored closelyComorbiditiesDiabetesHeart diseaseRenal disease
ECOG PS = Eastern Cooperative Oncology Group performance status.Rodriguez & Lilenbaum, 2008.
Performance status and the presence of comorbidities are important factors in determining whether patients are candidates for aggressive therapy for NSCLC (Rodriguez, Lilenbaum, 2008).
Patient Factors in Treatment PlanningPatient goals for treatmentQuality of life issues (eg, hair loss)Advanced directivesDemographicsSocial supportInvolve social workerCounseling servicesNutrition servicesFinancial issues
Addressing patient-related needs such as maintaining quality of life and the ability to perform activities of daily living is central to personalized NSCLC care.
Supportive Care ParadigmsBoth ASCO and NCCN recommend integration of palliative care into oncology practice Early palliative care leads to increase in overall survival (OS) in patients with metastatic NSCLC Increased quality of life, less depressive symptomsImproved understanding of diagnosis1/3 patients at diagnosis thought they had curable diseaseLess likely to receive chemotherapy near end of life
ASCO = American Society of Clinical Oncology; NCCN = National Comprehensive Cancer Network.Temel et al, 2011; Temel et al, 2010; Smith et al, 2012; NCCN, 2015b.
Compared with NSCLC patients who received standard care, patients who received early palliative care had less aggressive treatment at the end of life but longer survival (Temel et al, 2011; Temel at al, 2010).
Case Study 1: First-Line Treatment
Mrs. JF: History68-year-old woman, presented 1 month ago with pain in her lower backInitial management with nonsteroidal antiinflamatory drugs somewhat helpful; however, the pain persisted and an x-ray of the lower spine was orderedX-ray did not show bone abnormality but revealed a right lung mass at the right lung baseFurther imaging with positron emission tomography/computed tomography (PET/CT) revealed a right lung mass, mediastinal lymphadenopathy, bone metastases in the lumbar spine, and liver metastasesX-rays are often negative
Mrs. JF: Diagnostic EvaluationTreating physician referred the patient to a pulmonologist for a bronchoscopy with biopsyMediastinal lymph node was positive for NSCLC, adenocarcinoma histologyMagnetic resonance imaging (MRI) scan of the brain negative for metastatic diseaseBaseline labs within normal limitsBaseline PS 1What factors important in treatment planning?
Mrs. JF: Treatment ConsiderationsMolecular analysis: Do you have enough tissue? What to test for? Which are actionable?Smoking history?Comorbidities?Weight loss, hemoptysis?Goals of care, palliative care, incurable illness: Talk to your patient about these important, yet sensitive topics!
Mrs. JF: Treatment ConsiderationsBronchoscopy yielded core biopsy. Tissue was sent for full molecular analysis. Negative for EGFR, ALK, and ROS1 Patient has a 45-pack-year smoking history, currently trying to quitPatient has hypertension (controlled with medication), hypercholesterolemia, chronic obstructive pulmonary diseaseNo significant weight loss, no hemoptysisUnderstands incurable, no advanced directive, would like to fight
Mrs. JF: Treatment SelectionStandard chemotherapy in biomarker-negative patient appropriate therapyNumerous options available for chemotherapyPlatinum based chemotherapy appropriate given good PSIs hair loss an issue?Does she want to enroll in a clinical trial?NCCN, 2015b.
Mrs. JF: Treatment SelectionCisplatin vs. carboplatin? In US, carboplatin is often used in frontline therapyWhich drug to pair with carboplatin? Toxicity?PemetrexedPaclitaxelDocetaxelnab-paclitaxelGemcitabineVinorelbine
ECOG 1594: All Platinum Doublets Essentially Equal1,207 patients, stage IIIB/IV (15/85%), PS 0-2Median age 63; male/female: 64/36%
q3wAUC=6 mg/mL/min D1225 mg/m2/3h D1CarboplatinPaclitaxelq3w75 mg/m2 D175 mg/m2 D1CisplatinDocetaxelq4w100 mg/m2 D11 g/m2 D1,8,15CisplatinGemcitabineq3w75 mg/m2 D2135 mg/m2/24hCisplatinPaclitaxel
RANDOMIZE
AUC = area under the curve.Schiller et al, 2002.
Similar efficacy for all doublets
25Treatment of NSCLC with platinum-based doublets has reached a therapeutic plateau. In a large randomized trial (N=1,155), comparison of four platinum-based regimens showed that none offered a significant advantage over the others (Schiller et al, 2002).
Importance of HistologyPemetrexed/Cisplatin vs. Gemcitabine/Cisplatin
Gemcitabine/Cisplatin (n=863)Gemcitabine 1,250 mg/m2 IV D1 and D8Cisplatin 75 mg/m2 D1Every 21 days, max 6 cycles, vitamin and dexamethasone prophylaxisPemetrexed/Cisplatin (n=862)Pemetrexed 500 mg/m2 IVCisplatin 75 mg/m2 IVEvery 21 days, max 6 cycles, vitamin and dexamethasone prophylaxis
Study designMulticenter, randomized, open-labelNoninferiorityPrimary end pointOSSecondaryPFSTime to progressionObjective response rate Duration of responseToxicityRANDOMIZEDScagliotti et al, 2008.
Scagliotti and colleagues (2008) randomly assigned patients with advanced NSCLC to either pemetrexed/cisplatin or gemcitabine/cisplatin. The primary end point was overall survival.
Importance of HistologyOverall Survival Improved With Pemetrexed/Cisplatin vs.Gemcitabine/Cisplatin in First-Line Adenocarcinoma PatientsCI = confidence interval.Scagliotti et al, 2008; Scagliotti & Novello, 2003.
Median OS (months)(95% CI)12.6(10.7-13.6)10.9(10.2-11.9)
Pemetrexed/Cisplatin(n=436)
Gemcitabine/Cisplatin(n=411)
Overall survival was statistically superior for pemetrexed/cisplatin versus gemcitabine/ cisplatin in patients with adenocarcinoma (Scagliotti et al, 2008).27
Docetaxel + Cisplatin vs. Pemetrexed + Cisplatin in First-Line Non-Squamous NSCLCaStudy objectiveTo show the noninferiority of docetaxel + cisplatin compared with pemetrexed + cisplatin in patients with non-squamous NSCLCPrimary end point: PFS
Secondary end points: response rate, overall response rate, safetyR1:1Pemetrexed or EGFR-TKI or docetaxelKey patient inclusion criteria:Stage IV nonsquamous NSCLC Chemotherapy naiveECOG PS 0-2 (n=156)Pemetrexed 500 mg/m2 + cisplatin 70 mg/m2q3w, up to 4 cycles (n=80)Docetaxel 60 mg/m2 + cisplatin 70 mg/m2q3w, up to 4 cycles (n=76)StratificationECOG PS (0-1 vs. 2) and genderaThe trial was closed early due to slow accrual. Results should be interpreted with caution.Kim et al, 2014.
Kim and colleagues (2014) randomly assigned patients with non-squamous NSCLC to docetaxel/cisplatin or pemetrexed cisplatin.
Docetaxel + Cisplatin vs. Pemetrexed + Cisplatin: PFS and OSHR = hazard ratio.Kim et al, 2014.Partial remission was observed in 33.3% of patients who received docetaxel + cisplatin compared with 31.2% who received pemetrexed + cisplatin.
Docetaxel + cisplatin:28.0 months(95% CI 7.5, 48.5)Pemetrexed + cisplatin: 19.7 months(95% CI 10.8, 28.6)
02004006008001000DaysDocetaxel + cisplatin:4.6 months(95% CI 3.7, 5.6)Pemetrexed + cisplatin:4.7 months(95% CI 4.4, 5.1)
1.00.80.60.40.200100200300400500DaysHR 1.016 (95% CI 0.74, 1.40)OSPFS
Docetaxel + Cisplatin vs. Pemetrexed + Cisplatin: Toxicity
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