Lung cancer medical therapy

Lung cancer Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Lung cancer from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic study of choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography and Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Lung cancer medical therapy On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Lung cancer medical therapy All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Lung cancer medical therapy
CDC on Lung cancer medical therapy
Lung cancer medical therapy in the news
Blogs on Lung cancer medical therapy
Directions to Hospitals Treating Lung cancer
Risk calculators and risk factors for Lung cancer medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Saarah T. Alkhairy M.D; Anum Ijaz M.B.B.S., M.D.[2]

Overview

Medical therapy for lung cancer depends on tumor stage, histology (NSCLC vs SCLC), molecular profile, patient performance status, comorbidities, and treatment goals. Treatment modalities include surgery, radiation therapy, systemic therapy (chemotherapy, immunotherapy, targeted therapy), or combinations thereof. While the general framework does not differ between nonsmoking individuals and those with a history of smoking, nonsmoking individuals are more likely to have targetable genomic alterations such as EGFR mutations or ALK rearrangements, which influence treatment selection, particularly in advanced disease.

Medical Therapy

• The table below summarizes different treatment modalities for lung cancer.

Stage	Surgery	Radiotherapy	Targeted Therapy	Immunotherapy
Early Stage/Resectable Stage I–III	Preferred in persons who are medically eligible for surgery, with follow-up CT screening recommended every 6 months for 2-3 years.	Considered if unresectable or inoperable	EGFR-altered NSCLC: adjuvant osimertinib improves Disease free survival and Overall survival.,, ALK-rearranged NSCLC: adjuvant TKI (alectinib) improves Disease free survival.	Perioperative pembrolizumab improves OS in unselected stage II–IIIB NSCLC; benefit greatest in current smokers, uncertain in nonsmoking individuals. ,
Unresectable Locally Advanced/Metastatic Stage IIIB/IV	Not applicable	Concurrent chemoradiotherapy considered for lung cancers without actionable genomic alteration. ,	In metastatic NSCLC with actionable oncogenic alterations, targeted therapies are preferred as first-line systemic treatment EGFR-altered: first-line osimertinib improves PFS + OS; excellent intracranial control. ALK-rearranged: first-line lorlatinib improves 5-year Progression free survival. ROS1-rearranged: next-generation Tyrosine Kinase Inhibitors (repotrectinib or taletrectinib) with high response rates.,	Immunotherapy not primary modality in this subset; role not defined in EGFR/ALK populations.
Lung Cancer with Brain Metastasis; Oligometastasis( defined as 1-5 lesions).	Rare; considered in oligometastatic disease	For brain metastases: Stereotactic ablative radiotherapy (SABR) preferred to whole-brain radiotherapy to minimize central nervous system toxicity Oligometastatic Disease: SABR  in conjunction with systemic treatment improves overall survival but increases neurotoxicity.	Osimertinib and lorlatinib demonstrate strong CNS penetration and can be used instead of radiotherapy in selected patients with EGFR-mutated or ALK-rearranged NSCLC ,	Single-agent immunotherapy has limited efficacy in nonsmoking individuals and in tumors with EGFR mutations or ALK rearrangements . Single-agent PD-1/PD-L1 blockade should not be used for unresectable or metastatic EGFR- or ALK-altered NSCLC in nonsmoking individuals.

*Abbreviations. NSCLC=Nonsmall cell lung cancer; PFS= Progression free survival; OS= Overall survival

• The algorithm below demonstrates a treatment protocol for patients with stage I who can tolerate surgery: .

• The algorithm below demonstrates a treatment protocol for patients with stage II without invasion who can tolerate surgery:

• The algorithm below demonstrates a treatment protocol for patients with stage II with invasion who can tolerate surgery:

• The algorithm below demonstrates a treatment protocol for patients with stage III without invasion who can tolerate surgery:

• The algorithm below demonstrates a treatment protocol for patients with stage III with invasion who can tolerate surgery:
  

• The treatment of stage 4 lung cancers includes chemotherapy if the Eastern Cooperative Oncology Group (ECOG) Performance Scale is between 0 and 2. If the Performance Score is 3 or 4, then supportive care is recommended.

• The Eastern Cooperative Oncology Group (ECOG) Performance Scale is the following:

• • 0: Fully active
  • 1: Self-care activities but unable to do hard physical work
  • 2: Self-care activities but unable to do any work
  • 3: Unable to do any self-care activities or any work
  • 4: Fully disabled

Surgery

• To learn about the surgical approach to lung cancer, click here.

Radiation Therapy

• Radiation therapy can be administered via the following two methods:

1. External Beam Radiation Therapy (EBRT)

• This is more commonly used
• The body receives radiation from an outside machine
• The radiation is given in a series of sessions for about 8 weeks

2. Internal Radiation Therapy (Brachytherapy)

• This approach involves placing a radioactive object in or near the tumor
• This can shrink an airway blocking tumor

• Possible side effects include the following:

• Dry, sore, painful skin
• Hair loss
• Swelling of the lungs or esophagus
• Fatigue
• Loss of appetite

Chemotherapy for Non Small Cell Lung Cancer

Chemotherapy Regimens as Neo-adjuvant and Adjuvant Therapy

• Cisplatin 50 mg/m² days 1 and 8 AND vinorelbine 25 mg/m² days 1, 8, 15, 22, every 28 days for 4 cycles
• Cisplatin 100 mg/m² day 1 AND vinorelbine 30 mg/m² days 1, 8, 15, 22, every 28 days for 4 cycles
• Cisplatin 75 - 80 mg/m² day 1 AND vinorelbine 25 - 30 mg/m² days 1 + 8, every 21 days for 4 cycles
• Cisplatin 100 mg/m² day 1 AND etoposide 100 mg/m² days 1 - 3, every 28 days for 4 cycles
• Cisplatin 80 mg/m² days 1, 22, 43, 64 AND vinblastine 4 mg/m² days 1, 8, 15, 22, 29 then every 2 weeks after day 43, every 21 days for 4 cycles
• Cisplatin 75 mg/m² day 1 AND gemcitabine 1250 mg/m² days 1, 8, every 21 days for 4 cycles
• Cisplatin 75 mg/m² day 1 AND docetaxel 75 mg/m² day 1, every 21 days for 4 cycles
• Cisplatin 75 mg/m² day 1 AND pemetrexed 500 mg/m² day 1 for non-squamous (without specific histologic sub-type), every 21 days for 4 cycles

Chemotherapy Regimens for Patients with Comorbidities or Patients Not Able to Tolerate Cisplatin

• Paclitaxel 200 mg/m² day 1, carboplatin AUC 6 day 1, every 21 days

Concurrent Chemotherapy and Radiation Therapy Regimens

• Cisplatin 50 mg/m² on days 1, 8, 29, and 36 AND etoposide 50 mg/m² days 1 - 5, 29 - 33 WITH concurrent thoracic radiation therapy
• Cisplatin 100 mg/m² days 1 and 29 AND vinblastine 5 mg/m²/weekly x 5 WITH concurrent thoracic radiation therapy
• Carboplatin AUC 5 on day 1 AND pemetrexed 500 mg/m² on day 1 every 21 days for 4 cycles WITH concurrent thoracic radiation therapy
• Cisplatin 75 mg/m² on day 1 AND pemetrexed 500 mg/m² on day 1 every 21 days for 3 cycles WITH concurrent thoracic radiation therapy

Sequential Chemotherapy and Radiation Therapy Regimens

• Cisplatin 100 mg/m² on days 1 and 29 AND vinblastine 5 mg/m²/weekly on days 1, 8, 15, 22, and 29 FOLLOWED by radiation therapy
• Paclitaxel 200 mg/m² over 3 hours on day 1 AND carboplatin AUC 6 over 60 minutes on day 1 every 3 weeks for 2 cycles FOLLOWED by thoracic radiation therapy

Concurrent Chemotherapy and Radiation Therapy Followed by Chemotherapy

• Paclitaxel 45 - 50 mg/m² weekly AND carboplatin AUC 2 WITH concurrent thoracic radiation therapy FOLLOWED by 2 cycles of paclitaxel 200 mg/m² and carboplatin AUC 6
• Cisplatin 50 mg/m² on days 1, 8, 29, and 36 AND etoposide 50 mg/m² days 1 - 5, 29 - 33 WITH concurrent thoracic radiation therapy FOLLOWED by cisplatin 50 mg/m² and etoposide 50 mg/m² x 2

Chemotherapy for Non Small Cell Lung Cancer

Chemotherapy as Primary or Adjuvant Therapy

Limited Stage (Maximum of 4 - 6 cycles):

• Cisplatin 60 mg/m² day 1 AND etoposide 120 mg/m² days 1, 2, 31
• Cisplatin 80 mg/m² day 1 AND etoposide 100 mg/m² days 1, 2, 32
• Carboplatin AUC 5 - 6 day 1 AND etoposide 100 mg/m² days 1, 2, 33

Extensive Stage (Maximum of 4 - 6 cycles):

• Cisplatin 75 mg/m² day 1 AND etoposide 100 mg/m² days 1, 2, 3
• Cisplatin 80 mg/m² day 1 AND etoposide 80 mg/m² days 1, 2, 3
• Cisplatin 25 mg/m² days 1, 2, 3 AND etoposide 100 mg/m² days 1, 2, 3
• Carboplatin AUC 5 - 6 day 1 AND etoposide 100 mg/m² days 1, 2, 3
• Cisplatin 60 mg/m² day 1 AND irinotecan 60 mg/m² days 1, 8, 15
• Cisplatin 30 mg/m² AND irinotecan 65 mg/m² days 1, 89
• Carboplatin AUC 5 day 1 and irinotecan 50 mg/m² days 1, 8, 15

Subsequent Chemotherapy (Relapse < 2 - 3 Months)

• Paclitaxel
• Docetaxel
• Topotecan
• Irinotecan
• Temozolomide
• Gemcitabine
• Ifosfamide
• Bendamustine

Subsequent Chemotherapy (Relapse > 2 - 3 Months up to 6 Months)

• Topotecan
• Paclitaxel
• Docetaxel
• Irinotecan
• Gemcitabine
• Vinorelbine
• Oral etoposide
• Temozolomide
• Cyclophosphamide/doxorubicin/vincristine
• Bendamustine

Subsequent Chemotherapy (Relapse > 6 Months)

• Original regimen

Targeted Therapy

• In metastatic NSCLC with actionable oncogenic alterations, targeted therapies are preferred as first-line systemic treatment
• It is less likely to harm normal cells compared to chemotherapy.

The table below summarizes the targeted therapy drugs' mechanism of action and genomic alteration frequency by smoking status.

Genomic Alteration Frequency and FDA-Approved Drugs for Targeted Therapy in Lung Cancer ^a,b

Oncogene	Variation frequency in nonsmoking individuals, %	Variation frequency in people with a history of smoking, %c	Targetable alteration	FDA-approved drugs (target alteration)	Median overall survival, mo	Median progression-free survival, mo	Delivery route
EGFR	43	11	(1) Exon 19 deletion or exon 21 L858R	Afatinib (1,2) Aumatinvab (3) Dacomitinib (1,2) Erlotinib (1,2) Gefitinib (1,2)	27.9 NR 34.1 84.2 27	11.4 NR 14.7 10 9.2	Oral Intravenous Oral Oral Oral
			(2) S768I, L861Q, and/or G719X	Osimertinib (1,2)	38.6	18.9	Oral
			(3) Exon 20 insertion variation	Aumatinvab + chemotherapy	38.9	20.6	Oral
ALK	12	2	Rearrangement	Alectinib Brigatinib Certinib Crizotinib Ensartinib Lorlatinib	NR NR 51.3 NR NR NR	34.8 16.7 16.6 10.9 25.8 NR	Oral Oral Oral Oral Oral Oral
KRAS	9.10	29	G12C	Adagrasib Sotorasib	NR 12.5	7.4 6.3	Oral Oral
ROS1	3.22	1.11	Rearrangement	Entrectinib Crizotinib Repotrectinib Talretrectinib	47.8 NR NR NR	15.7 19.5 35.7 45.6	Oral Oral Oral Oral
ERBB2 (formerly HER2)	2.22	1.34	Variation	Fam-trastuzumab deruxtecan	17.8	8.2	Intravenous
RET	2	0.5	Rearrangement	Pralsetinib Salanectmians	21.2 NR	10.7 24	Oral Oral
BRAF	1.83	4.12	V600E	Encorafenib/binimetinib Dabrafenib/binimetinib	33.6 25.9	14.9 11.1	Oral Oral
MET	1.5	2.1	Exon 14 skipping	Capmatinib Tepotinib	20.8 29.7	10.8 15.9	Oral Oral
NRG1	0.18	0.08	Gene fusion	Zenocutuzumab	Not reported	6.8	Intravenous
NTRK	-0.174d		Gene fusion	Entrectinib Repotrectinib	41.5 NR	28 NR	Oral Oral
Abbreviations: FDA= Food and Drug Administration; NR= not reached( meaning data were too immature to calculate data) a Frequency data from whole-exome sequencing profiling of 160 people with lung cancer. b Nonsmoking individuals are defined as people who have smoked fewer than 100 cigarettes in their lifetime. People with a history of smoking are defined as people who currently or formerly smoked. c Smoking values are weighted averages among the people with a history of smoking categories. d Reliable data by smoking status not available.

References

Template:WikiDoc Sources