Non small cell lung cancer medical therapy metastatic cancer
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2] Maria Fernanda Villarreal, M.D. [3]
Overview
Therapies for non-small cell lung cancer stage IV include radiation therapy (for palliation) and palliative chemotherapy. The treatment of metastatic non-small cell lung cancer depends on the site and extension of the disease. If specific mutations are diagnosed, targeted treatment should be administered.
Local or Regional Recurrence
The algorithm below shows the approach for a local or regional recurrence of a non small cell lung cancers are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
What is the site of the recurrence? | |||||||||||||||||||||||||||||||||||||||||||
Bronchial obstruction | Mediastinal lymph node | Superior vena cava obstruction | Severe hemoptysis | Resectable tumor | |||||||||||||||||||||||||||||||||||||||
Surgical correction of the obstruction: laser therapy, stent or any other surgical procedure OR Radiation therapy (external-beam or brachytherapy) OR Photodynamic therapy | Has the patient received radiation therapy? | Chemotherapy + radiation therapy OR External-beam radiation therapy OR Superior vena cava stent collocation | Surgery OR Radiation therapy (external-beam or brachytherapy) OR Laser therapy, photodynamic therapy or tumor embolization | Tumor resection (preferred option) OR Radiation therapy (stereotactic ablative radiation therapy or external-beam radiation therapy) | |||||||||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||||||||||||
Administer systemic therapy (Click here for the treatment of metastatic disease) | Administer chemotherapy + radiation therapy | ||||||||||||||||||||||||||||||||||||||||||
Are findings suggestive of disseminated disease present? | |||||||||||||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||||||||||||
Click here for the treatment of metastatic disease | Observation OR Click here for the treatment of metastatic disease | ||||||||||||||||||||||||||||||||||||||||||
Systemic Metastasis
The algorithm bellow shows the approach for systemic metastasis of a non small cell lung cancers are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
What are the characteristics of the metastasis? | |||||||||||||||||||||||||||||||||||||||||||
Diffuse brain metastasis | Bone metastasis | Localized symptoms | Solitary metastasis | Multiple metastasis | |||||||||||||||||||||||||||||||||||||||
External-beam radiation therapy (palliative) | External-beam radiation therapy (palliative) + limb stabilization (prevention of pathological fractures) Denosumab or biophosphonate therapy should be considered | External-beamradiation therapy(palliative) | Click here for the treatment of stage IV M1b (solitary site metastasis) | Click here for the treatment of metastatic disease | |||||||||||||||||||||||||||||||||||||||
Click here for the treatment of metastatic disease | |||||||||||||||||||||||||||||||||||||||||||
Medical Therapy for Metastatic Non Small Cell Lung Cancer
The algorithms for the treatment of metastatic non small cell carcinoma of the lung are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
What the specific subtype according to the specific histological characteristics of the tumor? | |||||||||||||||||||||||||||||||||||||||||||||
| Squamous cell carcinoma | ||||||||||||||||||||||||||||||||||||||||||||
Is the patient a smoker or former smoker? | |||||||||||||||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||||||||||||||
Perform specific EGFR and ALK mutation testing: What is the specific mutation? | Perform specific EGFR and ALK mutation testing: Is there a mutation in any of those genes present? | ||||||||||||||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||||||||||||||
Sensitizing EGFR mutation | ALK mutation | Negative EGFR and ALK | Click here for the squamous cell carcinoma specific treatment | ||||||||||||||||||||||||||||||||||||||||||
Click here for the sensitizing EGFR mutation specific treatment | Click here for the specific therapy for the ALK mutation specific treatment | Click here for the treatment of negative sensitizing EGFR and ALK mutation metastatic disease | |||||||||||||||||||||||||||||||||||||||||||
Metastatic Adenocarcinoma, Large Cell Carcinoma and Not Specified Non-Small Cell Carcinoma
The algorithms for the treatment of metastatic adenocarcinoma, large cell carcinoma and not specified non small cell carcinoma of the lung are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
Positive Sensitizing EGFR Mutation
Was the mutation discovered before the initiation of first line therapy? | |||||||||||||||||||||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||||||||||||||||||||
Initiate erlotinib or afatinib | Suspend or complete chemotherapy and initiate erlotinib or afatinib OR Add erlotinib or afatinib to chemotherapy regimen | ||||||||||||||||||||||||||||||||||||||||||||||||||
Did the tumor progress or respond? | |||||||||||||||||||||||||||||||||||||||||||||||||||
Tumor progression | Positive response or stable tumor | ||||||||||||||||||||||||||||||||||||||||||||||||||
Symptomatic disease | Asymptomatic disease | ||||||||||||||||||||||||||||||||||||||||||||||||||
Systemic metastasis | Brain metastasis | Continue treatment | |||||||||||||||||||||||||||||||||||||||||||||||||
Multiple metastasis | Single metastasis | Multiple metastasis | Single metastasis | ||||||||||||||||||||||||||||||||||||||||||||||||
Continue treatment, consider local therapy | Continue treatment, consider whole brain radiation therapy | Continue treatment, consider local therapy | Consider platinum based chemotherapy with or without Bevacizumab AND/OR Erlotinib | ||||||||||||||||||||||||||||||||||||||||||||||||
If findings suggestive of progression of the disease are present, click here for the third line therapy | |||||||||||||||||||||||||||||||||||||||||||||||||||
Positive ALK Mutation
Was the mutation discovered before the initiation of first line therapy? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Initiate crizotinib | Suspend or complete chemotherapy and initiate crizotinib | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Did the tumor progress or respond? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Tumor progression | Positive response or stable tumor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symptomatic disease | Asymptomatic disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Systemic metastasis | Brain metastasis | Continue treatment or change to certinib according to the degree of disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Multiple metastasis | Single metastasis | Multiple metastasis | Single metastasis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Continue treatment, consider local therapy | Continue treatment, consider whole brain radiation therapy | Continue treatment, consider local therapy | Initiate certinib OR Consider platinum based chemotherapy with or without Bevacizumab AND/OR Erlotinib | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
If findings suggestive of progression of the disease are present, click here for the third line therapy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Negative EGRF and ALK or Unknown Mutation
What is the performance status (PS) of the patient? | |||||||||||||||||||||||||||||||||||||||||||||||
0-1 | 2 | 3-4 | |||||||||||||||||||||||||||||||||||||||||||||
Doublet chemotherapy OR Bevacizumab + Chemotherapy OR Cetuximab/vinorelbine/cisplatin | Chemotherapy | Supportive care | |||||||||||||||||||||||||||||||||||||||||||||
What was the tumor response to the treatment? | |||||||||||||||||||||||||||||||||||||||||||||||
Progression | Positive response or stable tumor | ||||||||||||||||||||||||||||||||||||||||||||||
Administer 4-6 cycles and assess progression of the disease | |||||||||||||||||||||||||||||||||||||||||||||||
PS 0-2 | PS 3-4 | Tumor progression | Positive response or stable tumor | ||||||||||||||||||||||||||||||||||||||||||||
Initiate docetaxel or pemetrexed or erlotinib or gemcitabine | Provide supportive care | Initiate docetaxel or pemetrexed or erlotinib or gemcitabine | Continuation maintenance (cetuximab or gemcitabine) OR Switch maintenance (erlotinib or decetaxel) OR Close observation | ||||||||||||||||||||||||||||||||||||||||||||
Initiate docetaxel or pemetrexed or erlotinib or gemcitabine | |||||||||||||||||||||||||||||||||||||||||||||||
If findings suggestive of progression of the disease are present, click here for the third line therapy | |||||||||||||||||||||||||||||||||||||||||||||||
Metastatic Squamous Cell Carcinoma
The algorithm for the treatment of metastatic squamous cell carcinoma are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
What is the performance status (PS) of the patient? | |||||||||||||||||||||||||||||||||||||||||||||||
0-1 | 2 | 3-4 | |||||||||||||||||||||||||||||||||||||||||||||
Cisplatin based chemotherapy OR Cetuximab/vinorelbine/cisplatin | Chemotherapy | Suportive care | |||||||||||||||||||||||||||||||||||||||||||||
What was the tumor response to the treatment? | |||||||||||||||||||||||||||||||||||||||||||||||
Progression | Positive response or stable tumor | ||||||||||||||||||||||||||||||||||||||||||||||
Administer 4-6 cycles and assess progression of the disease | |||||||||||||||||||||||||||||||||||||||||||||||
PS 0-2 | PS 3-4 | Tumor progression | Positive response or stable tumor | ||||||||||||||||||||||||||||||||||||||||||||
Initiate docetaxel or erlotinib or gemcitabine | Provide suportive care | Initiate docetaxel or erlotinib or gemcitabine | Continue treatment(cetuximab or gemcitabine) OR Switch mantainance (erlotinib or docetaxel) OR Close observation | ||||||||||||||||||||||||||||||||||||||||||||
Initiate docetaxel or pemetrexed or erlotinib or gemcitabine | |||||||||||||||||||||||||||||||||||||||||||||||
If findings suggestive of progression of the disease are present, click here for the third line therapy | |||||||||||||||||||||||||||||||||||||||||||||||
Third Line Therapy
The algorithm below shows the third line therapy for metastatic disease according to the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
What is the performance status of the patient? | |||||||||||||||||||||||||||||||
PS 0-2 | PS 3-4 | ||||||||||||||||||||||||||||||
If not previously used, administer any of the following:
| Administer erlotinib or provide suportive care | ||||||||||||||||||||||||||||||
What is the performance status of the patients after the treatment? | |||||||||||||||||||||||||||||||
PS 0-2 (stable tumor) | PS 3-4 (tumor progression) | ||||||||||||||||||||||||||||||
Provide supportive care or try experimental treatments | Provide supportive care | ||||||||||||||||||||||||||||||
Multiple Lung Cancers
The algorithm for the treatment of multiple non small cell lung cancers are based on the 2014 NCCN Non-Small Cell Lung Cancer guidelines.[1]
Is there suspicion of multiple lung cancers? | |||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||
Administer treatment according to the TNM stage of the tumor | |||||||||||||||||||||||||||||||||
Is the disease is confined to the chest or is there systemic proliferation? | |||||||||||||||||||||||||||||||||
Disease confined to the chest | Systemic proliferation | ||||||||||||||||||||||||||||||||
Assess the mediastinal lymph nodes in order to determine the N stage of the tumor | Click here for the treatment of systemic metastasis | ||||||||||||||||||||||||||||||||
What is the N stage of the tumor? | |||||||||||||||||||||||||||||||||
N0-1 | N2-3 | ||||||||||||||||||||||||||||||||
Is the patient symptomatic? | Click here for the treatment of systemic metastasis | ||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||
Is the lesion a solitary nodule or are there multiple nodules? | |||||||||||||||||||||||||||||||||
Solitary nodule | Multiple nodules | ||||||||||||||||||||||||||||||||
What is the risk of turning into a symptomatic disease? | |||||||||||||||||||||||||||||||||
High | Low | ||||||||||||||||||||||||||||||||
Is definitive local therapy possible? | Observation | ||||||||||||||||||||||||||||||||
No | Yes | ||||||||||||||||||||||||||||||||
Consider palliative chemotherapy with or without local Radiation therapy | Administer one of the following treatments:
| ||||||||||||||||||||||||||||||||
Click here for the treatment of systemic metastasis | Go to the appropriate algorithm according to the characteristics of the disease: local or regional recurrence or metastasis | ||||||||||||||||||||||||||||||||