Non-Small Cell Lung Cancer: Pharmacologic  Treatment

Lung cancer is the second most common cancer in the United States and estimated to account for 12.2% of new cancer cases in 2023.¹ According to the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute,  an estimated 20.8% of cancer deaths in 2023 will be attributed to lung and bronchus cancer.¹ Non-small cell lung cancer (NSCLC) is the most common type, accounting for 81% of all lung cancer diagnoses.²

The World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASCL) has categorized NSCLC into 3 main types according to prevalence: adenocarcinoma, which accounts for 40% of all lung cancers; squamous cell carcinoma, which makes up 25% of all lung cancers; and large cell carcinoma, which makes up 10% of all lung cancers.³ 

Additional NSCLC subtypes include adenosquamous, carcinoid, salivary gland, and sarcomatoid malignancies.³ Depending on the stage and location of NSCLC, a combination of surgery, radiation therapy, and pharmacotherapy is recommended to treat and manage the disease.^3,4 

Pharmacotherapy Recommendations for Non-Small Cell Lung Cancer

Below are details regarding chemotherapy, targeted therapy, and immunotherapy used to treat NSCLC. Each chart discusses the dosage, indicated uses, and treatment durations.

Chemotherapy

Chemotherapy involves treatment with cytotoxic drugs that interfere with DNA synthesis in mitosis to disrupt the cell cycle. These treatments target tumor cells and other rapidly dividing cells, forcing them to undergo apoptosis. The following chemotherapy agents are approved by the US Food and Drug Administration (FDA) to treat NSCLC. They are often combined with other chemotherapy agents or immunotherapy for neoadjuvant therapy or to help manage advanced or metastatic disease. The National Comprehensive Cancer Network (NCCN) provides recommendations for combination therapy based on the stage and purpose of treatment.⁵ 

Table 1. Management Guidelines for Chemotherapy Regimens for Non-Small Cell Lung Cancer

Drug	Dose	Administration	Treatment Duration	Recommended Use
Carboplatin	AUC 5-6	Reach desired AUC on day 1 of treatment	4 initial cycles administered before maintenance therapy; may depend on treatment combination	Neoadjuvant therapy prior to surgery, often combined with other chemotherapies; in combination with immunotherapy for patients with advanced or metastatic disease
Cisplatin	50-100 mg/m2	IV infusion on day 1 or days 1 and 8 depending on dosing and other combination therapies	4 initial cycles administered before maintenance therapy; may depend on treatment combination	Neoadjuvant therapy prior to surgery, often combined with other chemotherapies; in combination with immunotherapy for patients with advanced or metastatic disease
Docetaxel	75 mg/m2 May be combined with cisplatin 75 mg/m2 n	After failure of previous treatment: IV infusion over 1 h every 3 wk Chemotherapy-naive patients: IV infusion over 1 h followed by immediate infusion with cisplatin over 30-60 min every 3 wk	None indicated	Single agent for locally advanced or metastatic NSCLC after failing previous platinum-based chemotherapy treatment In combination with cisplatin for patients with locally advanced or metastatic NSCLC who have not received prior chemotherapy and who cannot be treated with surgery
Etoposide	100 mg/m2	IV infusion on days 1-3 for 28-d cycle	Total of 4 cycles	Neoadjuvant therapy prior to surgery, often combined with other chemotherapies; adjuvant therapy; in combination with other chemotherapies for patients with advanced or metastatic disease (contraindicated with PD-1/PD-L1 inhibitors)
Gemcitabine	21-d cycle: 1250 mg/m2 with cis[;atom 100 mg/m2  28-d cycle: 1000 mg/m2 with cisplatin 100 mg/m2	IV injection over 30 min, cisplatin is infused on day 1 following gemcitabine injection 21-d cycle: Injection on days 1 and 8 28-d cycle: Injection on days 1, 8, and 15	None indicated	First-line treatment in combination with cisplatin for locally advanced (stage IIIA or IIIB) or metastatic NSCLC that cannot be treated with surgery
Nab-paclitaxel (albumin-bound paclitaxel)	100 mg/m2	IV infusion over 30 minutes on days 1, 8, and 15 of 21-d cycle; carboplatin is administered immediately following nab-paclitaxel on day 1 of 21-d cycle	None indicated	First-line treatment in combination with carboplatin for locally advanced or metastatic NSCLC that cannot be treated with surgery or radiation therapy
Paclitaxel	175-200 mg/m2	IV infusion on day 1 of 21-d cycle	4 cycles total	Neoadjuvant therapy prior to surgery, often combined with other chemotherapies; in combination with immunotherapy for patients with advanced or metastatic disease
Pemetrexed	500 mg/m2	IV infusion over 10 min In combination with pembrolizumab and platinum-based chemotherapy: Infusion following pembrolizumab and prior to cisplatin or carboplatin on day 1 of 21-d cycle for 4 cycles total In combination with cisplatin for maintenance of nonsquamous disease or for recurrent disease: Infusion prior to cisplatin on day 1 of 21-d cycle for 4-6 cycles total	Treat until unacceptable toxicity occurs, disease progresses, or treatment cycles are complete	Treatment for nonsquamous NSCLC Initial treatment in combination with pembrolizumab and platinum chemotherapy for metastatic disease with no targetable EGFR or ALK mutationsInitial treatment in combination with cisplatin for locally advanced or metastatic diseaseMaintenance treatment as a single agent for locally advanced or metastatic disease that has not progressed after 4 cycles of platinum-based chemotherapy As a single agent for recurrent, metastatic disease after prior treatment with chemotherapy
Vinorelbine	Single agent: 30 mg/m2 With cisplatin 100 mg/m2: 25 mg/m2 With cisplatin 120 mg/m2: 30 mg/m2	IV infusion over 6-10 min Single agent: Infusion weekly With cisplatin 100 mg/m2: Infusion on days 1, 8, 15, and 22; cisplatin infusion on day 1 of 28-d cycle  With cisplatin 120 mg/m2: Infusion weekly; cisplatin infusion on days 1 and 29, then every 6 wk	None indicated	First-line treatment in combination with cisplatin for locally advanced or metastatic NSCLC Single agent for metastatic NSCLC

ALK = anaplastic lymphoma kinase; AUC = area under the curve; EGFR = epidermal growth factor receptor; IV = intravenous; NSCLC = non-small cell lung cancer; PD-1 = programmed death-1; PD-L1 = programmed death ligand-1. 

From NCCN treatment recommendations.⁵

From FDA-approved prescribing information.^6-14

Monoclonal Antibody Drugs

Monoclonal antibodies are protein drugs engineered to target a specific molecule or pathway used by cancer cells or tumors. In recent years, several monoclonal antibodies have been approved by the FDA for the treatment of NSCLC that targets driver mutations. Bevacizumab binds to and neutralizes vascular endothelial growth factor A (VEGF-A) to block angiogenesis in tumors.¹⁵ These therapies may be prescribed alone or in combination with chemotherapy for the treatment of NSCLC. 

Table 2. Management Guidelines for Monoclonal Antibody Drugs for Non-Small Cell Lung Cancer

Drug	Dose	Administration	Treatment Duration	Recommended Use
Amivantamab	Weight <80 kg: 1050 mg Weight >80 kg: 1400 mg	Premedicate prior to first infusion on days 1-2 of week 1 with:Antihistamine (25 or 50 mg)Acetaminophen (650-1000 mg)IV glucocorticoid (dexamethasone 10 mg or methylprednisolone 40 mg) Weekly IV infusion for weeks 1-4, then switch to biweekly infusions for weeks 5 and after	Treat until unacceptable toxicity occurs or disease progresses	Locally advanced or metastatic NSCLC with confirmed EGFR exon 20 insertion mutations with disease progression or after platinum-based chemotherapy
Bevacizumab	15 mg/kg	IV infusion every 3 wk in combination with paclitaxel and carboplatin; administer first infusion over 90 min, second infusion over 60 min if first infusion is tolerated, and subsequent infusions over 30 min if second infusion is tolerated	None indicated	First-line treatment for unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC in combination with paclitaxel and carboplatin
Necitumumab	800 mg	IV infusion over 60 min on days 1 and 8 of 3-wk cycles prior to cisplatin and gemcitabine infusions	Treat until unacceptable toxicity occurs or disease progresses	First-line treatment in combination with cisplatin and gemcitabine for metastatic squamous NSCLC (not indicated for non-squamous NSCLC)
Ramucirumab	10 mg/kg	Premedicate prior to ramucirumab infusion depending on patient’s history of infusion related reactions with:Antihistamine AcetaminophenIV glucocorticoid In combination with erlotinib: IV infusion every 2 wk over 60 min In combination with docetaxel: IV infusion over 60 min on day 1 of 21-d cycle prior to docetaxel infusion If first infusion over 60 min is tolerated, subsequent infusions may be 30 min	Treat until unacceptable toxicity occurs or disease progresses	First-line treatment in combination with erlotinib for metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations In combination with docetaxel for patients with metastatic NSCLC that has progressed on or after platinum-based chemotherapy; patients with targetable EGFR or ALK mutations should receive targeted therapy before receiving ramucirumab
Trastuzumab-deruxtecan	5.4 mg/kg	Administer prophylactic antiemetic medications prior to infusion to prevent delayed nausea or/or vomiting IV infusion once every 3 wk on a 21-day cycle	Treat until unacceptable toxicity occurs or disease progresses	Patients with unresectable or metastatic NSCLC with HER2 (ERBB2) mutations who have received ≥1 systemic therapy prior to treatment

ALK = anaplastic lymphoma kinase; IV = intravenous; EGFR = epidermal growth factor receptor; HER2 = human epidermal growth factor receptor-2; NSCLC = non-small cell lung cancer.

From FDA-approved prescribing information.^15-19

Immunotherapy

Immunotherapy focuses on activating a patient’s immune system against a cancer. Several immunotherapeutic agents for NSCLC target the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis on immune cells or cytotoxic T cells. Other immunotherapies work by interfering with the CTLA-4/B7 immune checkpoint. By blocking these interactions, T cells and other immune cells remain active and destroy cancer cells. 

Table 3. Management Guidelines for Immune Checkpoint Inhibitors for Non-Small Cell Lung Cancer

Drug	Dose	Administration	Treatment Duration	Recommended Use
Atezolizumab	840 mg, 1200 mg, or 1680 mg	IV infusion 840 mg every 2 wk, 1200 mg every 3 wk, or 1680 mg every 4 wk	Adjuvant therapy: Treat up to 1 y or until unacceptable toxicity occurs or disease recurs Metastatic NSCLC: Until unacceptable toxicity occurs or disease progresses	Single agent: Adjuvant treatment after resection and platinum-based chemotherapy for stage II to IIIA NSCLC with ≥1% PD-L1 expressionFirst-line treatment for patients with metastatic NSCLC whose tumors express high levels of PD-L1 (tumor cells ≥50% or immune cells ≥10% of the tumor area) with no targetable EGFR or ALK mutationsTreatment for metastatic NSCLC that has progressed during or after platinum-based chemotherapy; patients with targetable EGFR or ALK mutations should receive targeted therapy before receiving atezolizumab Combination therapy: First-line treatment in combination with carboplatin, bevacizumab, and paclitaxel for metastatic nonsquamous NSCLC with no targetable EGFR and ALK mutationsFirst-line treatment in combination with carboplatin and paclitaxel protein-bound for metastatic nonsquamous NSCLC with no targetable EGFR or ALK mutations
Cemiplimab	350 mg	IV infusion over 30 min every 3 wk	Treat until unacceptable toxicity occurs or disease progresses	First-line treatment in combination with platinum-based chemotherapy for NSCLC with no EGFR, ALK, or ROS1 mutations that is locally advanced but patients do not qualify for surgical resection or chemoradiation, or is metastatic Treatment as a single agent, first-line treatment for patients with NSCLC whose tumors express high levels of PD-L1 (TPS≥ 50%) and no EGFR, ALK, or ROS1 mutations that is locally advanced but patients do not qualify for surgical resection or chemoradiation, or is metastatic
Durvalumab	10 mg/kg or 1500 mg	IV infusion over 60 min every 2 wk (10 mg/kg) or every 5 wk (1500 mg)	Treat until unacceptable toxicity occurs or disease progresses, or for 12 mo maximum	Patients with unresectable stage III NSCLC whose disease has not progressed after treatment with concurrent radiation therapy and platinum-based chemotherapy Combined with tremelimumab-actl and platinum-based chemotherapy for metastatic NSCLC with no targetable EGFR or ALK mutations
Ipilimumab	Metastatic NSCLC expressing PD-L1: 1 mg/kg combined with nivolumab 360 mg/kg Metastatic or recurrent NSCLC: 1 mg/kg combined with nivolumab 360 mg/kg and platinum-doublet chemotherapy	IV infusion every 3 wk	Treat in combination with nivolumab until unacceptable toxicity occurs, disease progresses, or up to 2 y without disease progression	First-line treatment combined with nivolumab for patients with metastatic NSCLC whose tumors express ≥1% PD-L1 with no targetable EGFR or ALK mutations First-line treatment combined with nivolumab and 2 cycles of platinum-doublet chemotherapy for patients with metastatic or recurrent NSCLC with no targetable EGFR or ALK mutations
Nivolumab	Single agent: 240 mg or 480 mg  Combination therapy:Metastatic NSCLC expressing PD-L1: 360 mg with ipilimumab 1 mg/kg   Metastatic or recurrent NSCLC: 260 mg with ipilimumab 1 mg/kg and platinum-based doublet chemotherapy	IV infusion Single agent: Every 2 wk (240 mg) or 4 wk (480 mg) Combination therapy: Nivolumab every 3 wk and ipilimumab every 6 wkPlatinum-based doublet chemotherapy every 3 wk	Single agent: Treat until unacceptable toxicity occurs or disease progresses Combination therapy: Treat with ipilimumab until unacceptable toxicity occurs, disease progression, or up to 2 y in patients without disease progression	Neoadjuvant treatment with platinum-doublet chemotherapy for resectable NSCLC Single agent: Treatment of patients with metastatic NSCLC whose cancer progressed on or after platinum-based chemotherapy; patients with targetable EGFR or ALK mutations should receive targeted therapy before receiving nivolumab Treatment in combination with:Ipilimumab for first-line treatment in patients with metastatic or recurrent NSCLC whose tumors express  ≥1% PD-L1 with no targetable EGFR or ALK mutationsIpilimumab and 2 cycles of platinum-doublet chemotherapy for first-line treatment in patients with metastatic or recurrent NSCLC with no targetable EGFR or ALK mutations
Pembrolizumab	Adjuvant monotherapy: 200 mg or 400 mg In combination with chemotherapy: 200 mg or 400 mg	Adjuvant monotherapy: IV infusion every 3 wk (200 mg) or 6 wk (400 mg) In combination with chemotherapy: Administer pembrolizumab prior to chemotherapy when infused on the same day	Adjuvant therapy: Treat until disease recurrence, progression, unacceptable toxicity, or for 12 mo maximum In combination with chemotherapy: Treat until unacceptable toxicity occurs or disease progression, or for 24 mo maximum	Adjuvant therapy: Single agent following resection and platinum-based chemotherapy for stages IB, II, or IIIA NSCLC Single agent: First-line treatment for NSCLC expressing ≥1% PD-L1 that is stage III that cannot be treated with surgery or chemoradiation or is metastatic; tumors have no targetable EGFR or ALK mutations  Metastatic NSCLC for patients whose tumors express ≥1% PD-L1 with disease progression on or after platinum-based chemotherapy; patients with targetable EGFR or ALK mutations should receive targeted therapy before receiving pembrolizumab Combination therapy: First-line treatment with platinum-based chemotherapy and pemetrexed for metastatic, nonsquamous NSCLC with no targetable EGFR or ALK mutations First-line treatment with carboplatin and paclitaxel for metastatic squamous NSCLC
Tremelimumab	Non-squamous: tremelimumab 75 mg, durvalumab 1500 mg, and a combination of carboplatin and nab-paclitaxel OR carboplatin or cisplatin and pemetrexed Squamous: tremelimumab 75 mg, durvalumab 1500 mg, and carboplatin and nab-paclitaxel OR carboplatin or cisplatin and gemcitabine	Tremelimumab: IV infusion over 60 min every 3 wk Durvalumab: IV infusion over 60 min every 3 week Chemotherapy: IV infusion every 3 wk 21-d cycles; after cycle 5, infusions are every 4 wk; 8 cycles of treatment total	Treat with durvalumab until unacceptable toxicity occurs or disease progresses	In combination with durvalumab and platinum-based chemotherapy for metastatic NSCLC with no targetable EGFR or ALK mutations

ALK = anaplastic lymphoma kinase; EGFR = epidermal growth factor receptor; IV = Intravenous; NSCLC = non-small cell lung cancer; PD-l1 = programmed death ligand-1; TPS = tumor progression score.

From FDA-approved prescribing information.^20-26

Targeted Therapy for Actionable Driver Mutations in Non-Small Cell Lung Cancer

NSCLC often acquires driver mutations in receptor tyrosine kinases (RTKs) responsible for driving cellular growth and division. Researchers have developed several new tyrosine kinase inhibitors in recent years to target specific mutations in NSCLC. Many are used as second-line and third-line therapies as most patients become resistant to first-line therapies. Tyrosine kinase inhibitors are prescribed to treat advanced or metastatic NSCLC. The FDA has approved biomarker testing for certain treatments for NSCLC. 

Table 4. Management Guidelines for Targeted Therapies for Non-Small Cell Lung Cancer

Drug	Dosage*	Administration	Recommended Use Based on Drug Label
Adagrasib	600 mg twice daily	Tablet taken orally with or without food	Patients with locally advanced or metastatic NSCLC with a confirmed KRAS G12C mutation who have received ≥1 prior therapy
Afatinib	40 mg once daily	Tablet taken orally at least 1 h before or 2 h after eating	First-line treatment for metastatic NSCLC with non-resistant EGFR mutation
Alecitinib	600 mg twice daily	Capsule taken orally with food	Metastatic NSCLC with ALK mutation
Brigatinib	90 mg once daily	Tablet taken orally with or without food	Metastatic NSCLC with ALK mutation
Capmatinib	400 mg twice daily	Tablet taken orally with or without food	Metastatic NSCLC with MET exon 14 skipping mutation
Ceritinib	450 mg once daily	Gelatin capsule taken orally with food	Metastatic NSCLC with ALK mutation
Crizotinib	250 mg twice daily	Gelatin capsule taken orally with or without food	Metastatic NSCLC with ALK or ROS-1 mutation
Dabrafenib	150 mg twice daily	Capsules taken orally approximately 12 h apart, at least 1 h before or 2 h after eating	Metastatic NSCLC with BRAF V600E mutation
Dacomitinib	45 mg once daily	Tablet taken orally with or without food	First-line treatment for metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutation
Erlotinib	40 mg once daily	Tablet taken orally with or without food	First-line treatment of metastatic NSCLC with non-resistant EGFR mutation
Entrectinib	600 mg once daily	Hard capsule taken orally with or without food	Metastatic NSCLC with ROS1 mutation
Gefitinib	250 mg once daily	Tablet taken orally with or without food	First-line treatment of metastatic NSCLC with EGFR 19 deletion or exon 21 L858R substitution mutation
Larotrectinib	100 mg twice daily	Gelatin capsule taken orally with or without food	Metastatic NSCLC with NTRK gene fusion
Lorlatinib	100 mg once daily	Tablet taken orally with or without food	Metastatic NSCLC with ALK mutation
Mobocertinib	160 mg once daily	Capsule taken orally with or without food	Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutation with disease progression on or after platinum-based chemotherapy
Osimertinib	80 mg once daily or as adjuvant therapy up to 3 y	Tablet taken orally with or without food	Adjuvant therapy for patients with NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutation following tumor resection; first-line treatment for metastatic NSCLC with above mutations; metastatic NSCLC with EGFR T790M mutation following disease progression on or after EGFR TKI therapy
Pralsetinib	400 mg once daily	Capsule taken orally at least 2 h before or 1 h after eating	Metastatic NSCLC with RET fusion mutation
Selpercatinib	Weight <50 kg: 120 mg twice daily Weight >50 kg: 160 mg twice daily	Capsule taken orally with or without food; may be coadministered with food and a proton pump inhibitor, as needed	Locally advanced or metastatic NSCLC with RET fusion mutation
Sotorasib	960 mg once daily	Tablet taken orally with or without food	Locally advanced or metastatic NSCLC with KRAS G12C mutation following prior treatment with ≥1 systemic therapy
Tepotinib	450 mg once daily	Tablet taken orally with food	Metastatic NSCLC with MET exon 14 skipping mutation
Trametinib	2 mg once daily	Tablet taken orally at least 1 h before or 2 h after eating	Used in combination with dabrafenib to treat metastatic NSCLC with BRAF V600E mutation

*Treat until unacceptable toxicity occurs or disease progresses, unless otherwise noted.

ALK = anaplastic lymphoma kinase; EGFR = epidermal growth factor receptor; MET = mesenchymal epithelial transition factor. 

From FDA-approved prescribing information.^27-47

Monitoring Side Effects, Adverse Events, and Drug-Drug Interactions for Non-Small Lung Cancer Treatments

Discontinuation of pharmacologic treatment is most often due to intolerable side effects or severe adverse events due to toxicity. Although many treatments for NSCLC are targeted and exhibit few off-target effects, chemotherapy broadly targets rapidly dividing cells throughout the body. It is imperative that a patient’s overall health and other medications be taken into consideration to avoid side effects from treatment. 

The following tables provide an overview of the most common side effects and adverse events seen in clinical trials for non-small cell lung cancer. Considerations for special populations are also included. 

Table 5. Side Effect Profiles for Chemotherapy for Non-Small Cell Lung Cancer

Drug	Most Common Adverse Events	Drug-Drug Interactions	Special Population Considerations
Carboplatin	GI symptoms (nausea, vomiting, diarrhea, constipation), abdominal pain, decreased appetite, fever, rash, upper respiratory tract infection, cough, musculoskeletal pain, headache, back pain, joint pain, fatigue and weakness Warning: Infusion reaction	None indicated	Do not use in pregnant or breastfeeding patients
Cisplatin	Fever, myelosuppression, nausea, vomiting, peripheral neuropathy, increased risk of infection Warning: Infusion reaction, ototoxicity, ocular toxicity, nephrotoxicity, secondary leukemia	Nephrotoxic and ototoxic drugs	Do not use in pregnant or breastfeeding patients; use caution in patients with renal impairment
Docetaxel,	GI symptoms, infections, low blood cell count, neuropathy, dyspnea, dysgeusia, nail disorders, alopecia, myalgia, skin reactions, anorexia Warning: Hepatic impairment, hypersensitivity, skin and neurologic reactions, colitis, toxic death, eye disorders	CYP3A4 inhibitors or inducers	Do not use in pregnant or breastfeeding patients
Etoposide	Neutropenia, nausea, vomiting, dysphagia, abdominal pain, constipation, fever, optic neuritis	Warfarin	Do not use in pregnant or breastfeeding patients
Gemcitabine	Nausea, vomiting, leukopenia, neutropenia, thrombocytopenia, proteinuria, shortness of breath, rash, elevated aspartate transferase and alanine transferase levels	None indicated	Do not use in pregnant or breastfeeding patients
Paclitaxel	Neutropenia, thrombocytopenia, anemia, arthralgia/myalgia, nausea, vomiting, oral mucositis, neuromotor toxicity, neurosensory toxicity, cardiovascular events	CYP2C8 and CYP3A4 substrates, inhibitors, and inducers	Do not use in pregnant or breastfeeding patients
Nab-paclitaxel	Anemia, fatigue, nausea, low blood cell count, peripheral neuropathy, alopecia Warnings Severe myelosuppression, sepsis, severe neuropathy, hypersensitivity, pneumonitis	CYP2C8 and CYP3A4 inhibitors and inducers	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients; do not use in patients with severe hepatic impairment
Pemetrexed	GI symptoms, anorexia, fatigue, low blood cell count, stomatitis (oral mucositis) Warnings: Interstitial pneumonitis, skin complications, myelosuppression, renal failure	Ibuprofen	Do not use in pregnant or breastfeeding patients; do not use in patients with severe renal impairment
Vinorelbine	Injection site reaction, low blood cell count, elevated liver enzymes, nausea, vomiting, peripheral neuropathy Warnings: Neurologic, hepatic, and pulmonary toxicity; myelosuppression; bowel obstruction from severe constipation; extravasation	CYP3A inhibitors	Do not use in pregnant or breastfeeding patients; use with caution in patients with hepatic impairment

GI = gastrointestinal. From FDA-approved prescribing information.^6-14

Table 6. Side Effect Profiles of Monoclonal Antibody Drugs for Non-Small Cell Lung Cancer

Drug	Most Common Adverse Events	Drug-Drug Interactions	Special Population Considerations
Amivantamab	GI symptoms (nausea, vomiting, diarrhea, constipation), rash, musculoskeletal pain, edema, dyspnea, cough, fatigue, pruritus, paronychia Warning: Infusion reaction, interstitial lung disease, ocular toxicity, skin reactions	None indicated	Do not use in pregnant or breastfeeding patients
Bevacizumab	Fatigue, infection, headache, proteinuria  Warning: GI perforation, hemorrhage, venous thrombosis, hypertension, renal injury, infusion reaction, congestive heart failure, ovarian failure	None indicated	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients
Necitumumab	Rash, diarrhea, vomiting, stomatitis, weight loss, hemoptysis, headache, infections Warning: Hypomagnesemia, cardiopulmonary arrest, venous thrombosis, infusion reaction, skin complications	None indicated	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients
Ramucilumab	Infections, alopecia, diarrhea, stomatitis, proteinuria, epistaxis, pulmonary edema, headache Warning: GI perforation, hemorrhage, impaired wound healing, hypertension, venous thrombosis, infusion reaction, thyroid complications, nephrotoxicity	None indicated
Trastuzumab-deruxtecan	GI symptoms, abdominal pain, stomatitis, decreased appetite, alopecia, anemia, musculoskeletal pain, weight loss, infection, cough, dizziness, headache, peripheral neuropathy Warning: Interstitial lung disease, neutropenia, left ventricular dysfunction	None indicated	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients; monitor patients with hepatic and renal impairment

GI = gastrointestinal. From FDA-approved prescribing information.^15-19

Table 7. Side Effect Profiles for Immune Checkpoint Inhibitors for Non-Small Cell Lung Cancer

Drug	Most Common Adverse Events	Drug-Drug Interactions	Special Population Considerations
Atezolizumab,	GI symptoms (nausea, vomiting, diarrhea, constipation), decreased appetite, cough, dyspnea, fatigue, alopecia	None indicated	Do not use in pregnant or breastfeeding patients
Cemiplimab	Rash, pruritus, fatigue, musculoskeletal pain, diarrhea, nausea Warnings: Immune-related reactions, infusion-related reaction	None indicated	Do not use in pregnant or breastfeeding patients
Durvalumab	Cough, dyspnea, abdominal pain, diarrhea, rash, pruritus, pyrexia, fatigue, infections Warnings: Immune-related reactions, infusion-related reaction	None indicated	Do not use in pregnant or breastfeeding patients
Ipilimumab	GI symptoms, edema, fatigue, pyrexia, rash, pruritus, arthralgia, decreased appetite, abdominal pain, cough, dyspnea, infection, headache, thyroid complications Warnings: Immune-related reactions, infusion-related reaction	None indicated	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients
Nivolumab	GI symptoms, fatigue, decreased appetite, alopecia, rash, peripheral neuropathy, cough, dyspnea, thyroid complications Warnings: Immune-related reactions, infusion-related reaction	None indicated	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients, especially in combination with other therapies
Pembrolizumab,	GI symptoms, pyrexia, fatigue, rash, dyspnea, cough, decreased appetite Warnings: Immune-related reactions, infusion-related reaction	None indicated	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients
Tremelimumab	GI symptoms, cough, stomatitis, alopecia, rash, pruritus, hypothyroidism, pyrexia, fatigue, decreased appetite, musculoskeletal pain, infections, headache Warnings: Immune-related reactions, infusion-related reaction	None indicated	Do not use in pregnant or breastfeeding patients

GI = gastrointestinal. From FDA-approved prescribing information.^20-26

Table 8. Side Effect Profiles for Targeted Therapies for Non-Small Cell Lung Cancer

Drug	Most Common Adverse Events	Drug-Drug Interactions	Special Population Considerations
Adagrasib	GI symptoms (nausea, vomiting, diarrhea, constipation), musculoskeletal pain, fatigue, decreased appetite, edema, dyspnea, decreased blood cell count Warning: Renal impairment, hepatotoxicity, prolonged QT interval, ILD	Strong CYP3A4 inducers and inhibitors; sensitive CYP3A, CYP2C9, and CYP2D6 substrates; P-gp substrates; drugs that prolong QTc interval	Avoid breastfeeding during treatment
Afatinib	Diarrhea, stomatitis, cheilitis, skin rash, infections, rhinorrhea, weight loss, conjunctivitis, fever  Warning: ILD, gastrointestinal perforation, hepatotoxicity	P-gp inhibitors and inducers	Do not use in pregnant or breastfeeding patients; use with caution in patients with renal and hepatic impairment
Alecitinib	GI symptoms, fatigue, edema, rash, myalgia,  Warning: Vision problems, bradycardia, dysgeusia, hepatoxicity, elevated creatine phosphokinase levels, hemolytic anemia, renal impairment	None indicated	Do not use in pregnant or breastfeeding patients; use with caution in patients with hepatic impairment
Brigatinib	GI symptoms, dyspepsia, stomatitis, skin rash, cough, dyspnea, fever, edema, fatigue, myalgia, arthralgia, headache, dizziness, increased cholesterol levels, infections, decreased appetite Warning: Pulmonary embolism, bradycardia, ILD, vision problems, hypertension, elevated pancreatic enzymes, hyperglycemia, hepatotoxicity	Moderate or strong CYP3A inhibitors and inducers	Do not use in pregnant or breastfeeding patients
Capmatinib	GI symptoms, fever, weight loss, musculoskeletal pain, edema, fatigue, decreased appetite, cough, dyspnea, skin rash, dizziness Warning: ILD, hepatoxicity, pancreatic toxicity, hypersensitivity reaction	Moderate or strong CYP3A inhibitors and inducers; CYP1A2 substrates; P-gp substrates; MATE1 and MATE2K substrates	Do not use in pregnant or breastfeeding patients
Ceritinib	GI symptoms, weight loss, decreased appetite Warning: ILD, prolonged QT interval, bradycardia, hepatotoxicity, hyperglycemia, pancreatitis	Strong CYP3A4 inhibitors and inducers; P-gp inhibitors; warfarin; drugs that prolong QTc interval or cause bradycardia	Do not use in pregnant or breastfeeding patients
Crizotinib	GI symptoms, vision disorders, fatigue, decreased appetite, neuropathy, infections, dizziness, edema, elevated transaminases Warning: ILD, severe vision loss, prolonged QT interval, hepatotoxicity, bradycardia	Moderate or strong CYP3A inhibitors and inducers; drugs that prolong QTc interval or cause bradycardia	Do not use in pregnant or breastfeeding patients; use with caution in patients with hepatic and renal impairment
Dabrafenib	Diarrhea, fever, vomiting, neutropenia, chills, pyrexia, respiratory distress, decreased appetite, skin rash Warning: New primary malignancies, hemorrhage, uveitis, skin toxicity, hyperglycemia, G6PD deficiency, cardiomyopathy	Strong CYP3A4 and CYP2C8 inhibitors; warfarin; midazolam; dexamethasone; hormonal contraceptives	Do not use in pregnant or breastfeeding patients; use with caution in patients with hepatic impairment
Dacomitinib	Rash, diarrhea, stomatitis, paronychia, dry skin, weight loss, stomatitis, cough, pruritus, alopecia, ILD	Avoid concomitant use with PPIs; CYP2D6 substrates	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients
Erlotinib	Diarrhea, rash, cough, dyspnea, decreased appetite, asthenia Warning: ILD, renal failure, gastrointestinal perforation, hepatotoxicity, hemolytic anemia with thrombocytopenia, hemorrhage	Strong CYP3A4 inhibitors or combined CYP3A4 and CYP1A2 inhibitors; CYP3A4 inducers; PPIs; anticoagulants	Do not use in pregnant or breastfeeding patients
Entrectinib	GI symptoms, abdominal pain, fatigue, pyrexia, edema, dysgeusia, dizziness, cognitive impairment, headache, cough, dyspnea, myalgia, arthralgia, weight gain, infections, hypotension, skin rash Warning: Congestive heart failure, CNS effects, hepatotoxicity, skeletal fractures, prolonged QT interval, vision disorders, hyperuricemia	Moderate and strong CYP3A inhibitors and inducers; drugs that prolong QT interval	Do not use in pregnant or breastfeeding patients
Gefitinib	Diarrhea, vomiting, stomatitis, decreased appetite Warning: ILD, hepatotoxicity, skin and eye disorders, GI perforation	CYP3A4 inducers and inhibitors; drugs affecting gastric pH; warfarin	Do not use in pregnant or breastfeeding patients; use with caution in patients with hepatic impairment
Larotrectinib	GI symptoms, anemia, elevated liver enzymes, fatigue, musculoskeletal pain, pyrexia, dizziness, low blood cell count Warnings: Skeletal fractures, CNS effects, hepatotoxicity	Moderate or strong CYP3A4 inhibitors and inducers; sensitive CYP3A4 substrates	Do not use in pregnant or breastfeeding patients
Lorlatinib	Diarrhea, edema, weight gain, peripheral neuropathy, fatigue, dyspnea, cough, mood changes, cognitive effects, arthralgia, hypertriglyceridemia, hypercholesterolemia	Moderate or strong CYP3A inhibitors and inducers; fluconazole; certain CYP3A and P-gp substrates	Do not use in pregnant or breastfeeding patients; reduce dose in patients with severe renal impairment
Mobocertinib	GI symptoms, decreased appetite, skin rash and pruritus, infections, musculoskeletal pain, cough, dyspnea, fatigue, rhinorrhea Warning: ILD, cardiotoxicity, prolonged QTc interval	Moderate or strong CYP3A inhibitors or inducers; CYP3A substrates; drugs that prolong QTc interval	Do not use in pregnant or breastfeeding patients
Osimertinib	Diarrhea, stomatitis, musculoskeletal pain, dry skin, paronychia, cough, fatigue, low blood cell count Warning: ILD, cardiomyopathy, prolonged QTc interval, skin complications, aplastic anemia	Strong CYP3A inducers; BCRP or P-gp substrates; drugs that prolong QTc interval	Do not use in pregnant or breastfeeding patients; use with caution in geriatric patients
Pralsetinib	Diarrhea, constipation, fatigue, musculoskeletal pain, hypertension, low blood cell count, increased liver enzyme levels Warning: ILD, hepatotoxicity, tumor lysis syndrome, impaired wound healing, hypertension, hemorrhaging	Strong CYP3A inhibitors and inducers; combined P-gp and strong CYP3A inhibitors	Do not use in pregnant or breastfeeding patients; use with caution in patients with hepatic impairment
Selpercatinib	GI symptoms, dry mouth, rash, headache, edema, hypertension, abdominal pain, low blood cell count, elevated liver enzyme levels	Drugs affecting gastric pH; moderate or strong CYP3A inhibitors or inducers; CYP2C8, CYP3A, and P-gp substrates; drugs that prolong QT interval	Do not use in pregnant or breastfeeding patients; reduce dose in patients with severe hepatic impairment
Sotorasib	Nausea, diarrhea, fatigue, musculoskeletal pain, cough, decreased blood cell count, increased liver enzyme levels Warning: ILD, hepatotoxicity	Drugs affecting gastric pH; strong CYP3A4 inducers and substrates; P-gp substrates; BCRP substrates	None indicated
Tepotinib	Nausea, diarrhea, edema, dyspnea, fatigue, musculoskeletal pain, decreased blood cell count, increased liver enzyme levels Warning: ILD, hepatotoxicity	P-gp substrates	Do not use in pregnant or breastfeeding patients
Trametinib	GI symptoms, pyrexia, dry skin, fatigue, decreased appetite, cough, dyspnea, rash, chills, edema, hemorrhage Warning: New primary malignancies, gastrointestinal complications, cardiomyopathy, venous thrombosis, skin toxicity, hyperglycemia, ocular toxicity	Trametinib is prescribed with dabrafenib; refer to dabrafenib prescribing information	Do not use in pregnant or breastfeeding patients; reduce dose in patients with moderate to severe hepatic impairment

BCRP = breast cancer resistant protein; CNS = central nervous system; G6PD = glucose-6-phosphate dehydrogenase; GI = gastrointestinal; ILD = Interstitial lung disease; P-gp = P-glycoprotein; PPIs = proton pump inhibitors

From FDA-approved prescribing information.^27-47

References

1. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: lung and bronchus cancer. National Cancer Institute. Accessed May 3, 2023. https://seer.cancer.gov/statfacts/html/lungb.html 
2. Lung cancer — non-small cell: statistics.  ASCO Cancer.net. Updated March 2023. Accessed May 11, 2023.  https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics
3. Non-Small Cell Lung Cancer Treatment (PDQ^®)-Health Professional Version. National Cancer Institute. Updated February 17, 2023. Accessed May 4, 2023. https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq#_470 
4. Ettinger DS, Wood DE, Aisner DL, et al. Non-small cell lung cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(5):497-530. doi:10.6004/jnccn.2022.0025
5. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Non-Small Cell Lung Cancer. Updated April 13, 2023. Accessed May 3, 2023. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf 
6. Cisplatin. Prescribing information. Fresenius Kabi USA, LLC. Updated December 31, 2019. Accessed May 5, 2023. 
7. Carboplatin. Prescribing information.  Fresenius Kabi USA, LLC. Updated July 7, 2021. Accessed May 5, 2023. 
8. Docetaxel anhydrous. Prescribing information. Curae Pharma360, Inc. Updated October 18, 2022. Accessed May 3, 2023. 
9. Etoposide. Prescribing information. Fresenius Kabi USA, LLC. Updated June 2, 2022. Accessed May 5, 2023. 
10. Gemcitabine. Prescribing information. Armas Pharmaceuticals, Inc. Updated January 4, 2020. Accessed May 3, 2023. 
11. Paclitaxel. Prescribing information. Alembic Pharmaceuticals Inc. Updated October 27, 2022. Accessed May 3, 2023. 
12. Abraxane. Abraxis BioScience, LLC. Updated October 31, 2022. Accessed May 3, 2023. 
13. Alimta. Prescribing information. Eli Lilly and Company. Updated August 31, 2022. Accessed May 3, 2023. 
14. Vinorelbine. Prescribing information. Actavis Pharma, Inc. Updated May 31, 2022. Accessed May 3, 2023. 
15. Avastin. Prescribing information. Genentech, Inc. September 23, 2022. Accessed May 3, 2023. 
16. Rybrevant. Prescribing information. Janssen Biotech, Inc. Updated November 9, 2022. Accessed May 3, 2023. 
17. Portrazza. Prescribing information. Eli Lilly and Company. Updated May 3, 2017. Accessed May 3, 2023. 
18. Cyramza. Prescribing information. Eli Lilly and Company. Updated November 8, 2022. Accessed May 3, 2023. 
19. Erhertu. Prescribing information. Daiichi Sankyo, Inc. Updated February 8, 2023. Accessed May 3, 2023. 
20. Tecentriq. Prescribing information. Genentech, Inc. Updated December 14, 2022. Accessed May 3, 2023. 
21. Libtayo. Prescribing information. Regeneron Pharmaceuticals, Inc. April 28, 2023. Accessed May 3, 2023. 
22. Imfinzi. Prescribing information. AstraZeneca Pharmaceuticals LP. Updated November 10, 2022. Accessed May 3, 2023. 
23. Yervoy. Prescribing information. E.R. Squibb & Sons, L.L.C. Updated February 15, 2023. Accessed May 3, 2023. 
24. Opdivo. Prescribing information. E.R. Squibb & Sons, L.L.C. Updated February 15, 2023. Accessed May 3, 2023. 
25. Keytruda. Prescribing information. Merck Sharp & Dohme LLC. Updated April 3, 2023. Accessed May 3, 2023. 
26. Imjudo. Prescribing information. AstraZeneca Pharmaceuticals LP. Updated November 10, 2022. Accessed May 3, 2023. 
27. Krazati. Prescribing information. Mirati Therapeutics, Inc. December 10, 2021. Updated December 10, 2021. Accessed May 3, 2023. 
28. Gilotrif. Prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. Updated July 11, 2022. Accessed May 3, 2023. 
29. Alecensa. Prescribing information. Genentech, Inc. Updated June 16, 2022. Accessed May 3, 2023. 
30. Alunbrig. Prescribing information. Takeda Pharmaceuticals America, Inc. Updated October 25, 2022. Accessed May 3, 2023. 
31. Tabrecta. Prescribing information. Novartis Pharmaceuticals Corporation. Updated March 24, 2023. Accessed May 3, 2023. 
32. Zykadia. Prescribing information. Novartis Pharmaceuticals Corporation. Updated June 7, 2022. Accessed May 3, 2023.  
33. Xalkori. Prescribing information. Pfizer Laboratories Division of Pfizer Inc. Updated October 3, 2022. Accessed May 3, 2023. 
34. Tafinlar. Prescribing information. Novartis Pharmaceuticals Corporation. April 20, 2023. Accessed May 3, 2023. 
35. Vizimpro. Prescribing information. Pfizer Laboratories Div Pfizer Inc. Updated December 23, 2020. Accessed May 3, 2023. 
36. Tarceva. Prescribing information. Genentech, Inc. Updated December 12, 2018. Accessed May 3, 2023. 
37. Rozlytrek. Prescribing information. Genentech, Inc. Updated June 8, 2020. Accessed May 3, 2023. 
38. Iressa. Prescribing information. AstraZeneca Pharmaceuticals LP. Updated February 28, 2023. Accessed May 3, 2023. 
39. Vitrakvi. Prescribing information. Bayer HealthCare Pharmaceuticals Inc. Updated December 6, 2022. Accessed May 3, 2023. 
40. Lorbrena. Pfizer Laboratories Div Pfizer Inc. Updated February 1, 2021. Accessed May 3, 2023. 
41. Exkivity. Prescribing information. Takeda Pharmaceuticals America, Inc. March 7, 2023, Accessed May 3, 2023. 
42. Tagrisso. Prescribing information. AstraZeneca Pharmaceuticals LP. October 21, 2022. Accessed May 3, 2023. 
43. Gavreto. Prescribing information. Genentech, Inc. Updated February 8, 2022. Accessed May 3, 2023. 
44. Retevmo. Prescribing information. Eli Lilly and Company. Updated September 21, 2022. Accessed May 3, 2023. 
45. Lumakras. Prescribing information. Amgen Inc. Updated February 2, 2023. Accessed May 3, 2023. 
46. Tepmetko. Prescribing information. EMD Serono, Inc. Updated March 30, 2023. Accessed May 3, 2023. 
47. Mekinist. Prescribing information. Novartis Pharmaceuticals Corporation. Updated March 16, 2023. Accessed May 3, 2023. 

Author Bio

Emily Wagner, MS earned a Bachelor of Science in biotechnology from the Rochester Institute of Technology in 2018 and a Master of Science in biomedical sciences with a focus in pharmacology from the University of Colorado Anschutz Medical Campus in 2020. During her thesis work, she studied non-small cell lung cancer and how the immune system plays a role in response to different treatments. Emily currently lives in Colorado where she enjoys the mountains, spending time with her dog, baking, and reading a good book.