Lung Cancer:

NSCLC(Non-small Cell Lung Cancer)

Gregory Butler, PharmD Candidate 2020MCPHS University

OBJECTIVES▹ Discuss the epidemiology, etiology, and

pathophysiology of non-small cell lung cancer (NSCLC)

▹ Review appropriate treatment options for different presentations of NSCLC

▹ Describe example maintenance therapies, monitoring, and side-effect management of NSCLC treatment

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Background3

Epidemiology: Lung cancer is the leading cause of cancer-related death in the US and much of the world. The majority of cases are NSCLC, approximately 80%.

Etiology: Tobacco smoke is a known carcinogen to the lungs, and the most significant risk factor. Environmental substances also contribute including arsenic and asbestos.

Pathophysiology: Genetic lesions to bronchial epithelial cells lead to a variety of phenotypes each with specific treatment options

Lung Cancer4

NSCLC ~ 80% SCLC ~ 20%

Non-SquamousAdenocarcinoma/Large Cell

Squamous

Localized Regional Metastatic(Resectable: goal is to CURE with surgery, radiation, chemo)

(Not resectable: goal is to CURE with chemo-radiation + Durvalumab consolidation)

Stages & Chemotherapy

▹ Stage I▹ Stage II▹ Stage IIIa

For resected II and IIIa, chemotherapy may includeCisplatinOr +Carboplatin(for pts with CKD or HF)

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VinorelbineEtoposideGemcitabineDocetaxilPemetrexed (Nonsquamous)

Nephrotoxicity with Cisplatin and Carboplatin6

Monitor for signs:● Decreased urine output (>125 mL/h)● Increased SCr● Decreased Mg & K

Oxaliplatin has the lowest risk of nephrotoxicity

Stages &

▹ Stage IVTARGETS: FIRST-LINE-inibs:EGFR - OsimertinibALK - AlectinibROS1 - CrizotinibBRAF - Dabrafenib + TramNTRK - Larotrec

PD-L1 Expression...

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VinorelbineEtoposideGemcitabineDocetaxilPemetrexed (Nonsquamous)

PD-L1 First-line therapy8

Pembrolizumab (Keytruda) has been shown to be of equal efficacy to chemotherapy in patients with PD-L1 TPS >1% with a much more benign SE profile

MaintenanceTherapy for metastatic NSCLC

PD-L1 >1%Pembrolizumab 1st line▹ After 4-6 cycles, assessed

for a response. Maintenance tx includes▸ Continuation, switch,

observation

Targeted(EGFR, ALK, ROS, BRAF, NTRK)▹ Continue therapy

until progression

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Sick of Keytruda?Looking for the best immune-checkpoint inhibitor in NSCLC patients?

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Patient population: NSCLC w/ PD-L1 expressionIntervention: PembrolizumabComparator: Other immune checkpoint inhibitorsOutcome: Survival

Selecting the evidence:

Search results:52 peer-reviewed articles were located, including new clinical trials, systematic reviews, and meta-analyses.

Form of literature:We will choose a meta-analysis given the volume of trials to be evaluated, and offer the broadest view of potential treatment options

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Picking a paper:Four such studies match our specific criteria, two were excluded for not comparing individual immune-checkpoint inhibitors

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“Nivolumab versus pembrolizumab. The results of our analysis did not show any significant differences in the efficacy endpoints (ORR, PFS, OS) between these two

anti-PD1inhibitors, even if considering only the PD–L11 population. Nivolumab was associated with a significant

reduction of G3/G5 AEs (RR 0.41, 95% CI 0.29–0.60)”

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Looking for the best immune-checkpoint inhibitor in NSCLC patients?

Passiglia F, Galvano A, Rizzo S, et al. Looking for the best immune-checkpoint inhibitor in pre-treated NSCLC patients: An indirect comparison between nivolumab, pembrolizumab and atezolizumab. Int J Cancer. 2018;142(6):1277-1284.

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“DISCUSSION: ICIs improve survival in previously treated advanced NSCLC patients across PD-L1 expression levels compared to docetaxel. There is a positive dose-response

relationship between PD-L1 expression and survival benefits, and little evidence of survival differences between

nivolumab, pembrolizumab and atezolizumab.”

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Any differences at all when comparing their effectiveness?

Tan PS, Aguiar P, Haaland B, Lopes G. Comparative effectiveness of immune-checkpoint inhibitors for previously treated advanced non-small cell lung cancer - A systematic review and network meta-analysis of 3024 participants. Lung Cancer. 2018;115:84-88.

Decision pointWeighing the benefits and risks, expenses and availability, pharmacists are qualified to recommend the most appropriate choice of therapy, contingent that the patient needs come first.

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Questions?

References:

▹ National Comprehensive Cancer Network. Non-small Cell Lung Cancer. http://www.nccn.org/professionals/physician_gls/pdf/nsclc.pdf. Accessed October 15, 2019

▹ Passiglia F, Galvano A, Rizzo S, et al. Looking for the best immune-checkpoint inhibitor in pre-treated NSCLC patients: An indirect comparison between nivolumab, pembrolizumab and atezolizumab. Int J Cancer. 2018;142(6):1277-1284.

▹ Tan PS, Aguiar P, Haaland B, Lopes G. Comparative effectiveness of immune-checkpoint inhibitors for previously treated advanced non-small cell lung cancer - A systematic review and network meta-analysis of 3024 participants. Lung Cancer. 2018;115:84-88.

▹ DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T114774, Non-small Cell Lung Cancer; [updated 2018 Dec 04, cited place cited date here]. Available from https://www-dynamed-com.ezproxymcp.flo.org/topics/dmp~AN~T114774. Registration and login required.

▹ DiPiro, Joseph T. Pharmacotherapy-- a Pathophysiologic Approach. McGraw-Hill Education, 2017.

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