Treatment Option Overview for NSCLC

Treatment Option Overview for NSCLC

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In NSCLC, results of standard treatment are poor except for the most localized cancers. All newly diagnosed patients with NSCLC are potential candidates for studies evaluating new forms of treatment.

Surgery is the most potentially curative therapeutic option for this disease. Postoperative chemotherapy may provide an additional benefit to patients with resected NSCLC. Radiation therapy combined with chemotherapy can produce a cure in a small number of patients and can provide palliation in most patients. Prophylactic cranial irradiation (PCI) may reduce the incidence of brain metastases, but there is no evidence of a survival benefit and the effect of PCI on quality of life is not known.[1,2] In patients with advanced-stage disease, chemotherapy or epidermal growth factor receptor (EGFR) kinase inhibitors offer modest improvements in median survival, though overall survival is poor.[3,4]

Chemotherapy has produced short-term improvement in disease-related symptoms in patients with advanced NSCLC. Several clinical trials have attempted to assess the impact of chemotherapy on tumor-related symptoms and quality of life. In total, these studies suggest that tumor-related symptoms may be controlled by chemotherapy without adversely affecting overall quality of life;[5,6] however, the impact of chemotherapy on quality of life requires more study. In general, medically fit elderly patients with good performance status obtain the same benefits from treatment as younger patients.

The identification of mutations in lung cancer has led to the development of molecularly targeted therapy to improve the survival of subsets of patients with metastatic disease.[7] In particular, genetic abnormalities in EGFR, MAPK, PI3K signaling pathways in subsets of NSCLC may define mechanisms of drug sensitivity and primary or acquired resistance to kinase inhibitors. EGFR mutations strongly predict the improved response rate and progression-free survival of inhibitors of EGFR. Fusions ofALK with EML4 genes form translocation products that occur in ranges from 3% to 7% in unselected NSCLC and are responsive to pharmacological inhibition of ALK by agents such as crizotinib. METoncogene encodes hepatocyte growth factor receptor. Amplification of this gene has been associated with secondary resistance to EGFR tyrosine kinase inhibitors.

The standard treatment options for each stage of NSCLC are presented in Table 11.

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Table 11. Standard Treatment Options for NSCLC
Stage (TNM Staging Criteria)		Standard Treatment Options
Occult NSCLC		Surgery
Stage 0 NSCLC		Surgery
		Endobronchial therapies
Stages IA and IB NSCLC		Surgery
		Radiation therapy
Stages IIA and IIB NSCLC		Surgery
		Neoadjuvant chemotherapy
		Adjuvant chemotherapy
		Radiation therapy
Stage IIIA NSCLC	Resected or resectable disease	Surgery
		Neoadjuvant therapy
		Adjuvant therapy
	Unresectable disease	Radiation therapy
		Chemoradiation therapy
	Superior sulcus tumors	Radiation therapy alone
		Radiation therapy and surgery
		Concurrent chemotherapy with radiation therapy and surgery
		Surgery alone (for selected patients)
	Tumors that invade the chest wall	Surgery
		Surgery and radiation therapy
		Radiation therapy alone
		Chemotherapy combined with radiation therapy and/or surgery
Stage IIIB NSCLC		Sequential or concurrent chemotherapy and radiation therapy
		Chemotherapy followed by surgery (for selected patients)
		Radiation therapy alone
Stage IV NSCLC		Cytotoxic combination chemotherapy (first line)
		Combination chemotherapy with bevacizumab or cetuximab
		EGFR tyrosine kinase inhibitors (first line)
		EML4-ALK inhibitors in patients with EML-ALK translocations
		Maintenance therapy following first-line chemotherapy
		Endobronchial laser therapy and/or brachytherapy (for obstructing lesions)
		External-beam radiation therapy (primarily for palliation of local symptomatic tumor growth)
Recurrent NSCLC		Radiation therapy (for palliation)
		Chemotherapy or kinase inhibitors alone
		EGFR inhibitors in patients with/without EGFR mutations
		EML4-ALK inhibitors in patients with EML-ALK translocations
		Surgical resection of isolated cerebral metastasis (for highly selected patients)
		Laser therapy or interstitial radiation therapy (for endobronchial lesions)
		Stereotactic radiation surgery (for highly selected patients)

In addition to the standard treatment options presented in Table 11, treatment options under clinical evaluation include the following:

·         Combining local treatment (surgery).

·         Regional treatment (radiation therapy).

·         Systemic treatments (chemotherapy, immunotherapy, and targeted agents).

·         Developing more effective systemic therapy.

Follow-Up

Several small series have reported that reduction in fluorodeoxyglucose-positron emission tomography (FDG-PET) after chemotherapy, radiation therapy, or chemoradiation therapy correlates with pathological complete response and favorable prognosis.[8-15] Studies have used different timing of assessments, FDG-PET parameters, and cutpoints to define FDG-PET response. Reduction in maximum standardized uptake value (SUV) of more than 80% predicted for complete pathological response with a sensitivity of 90%, specificity of 100%, and accuracy of 96%.[16] Median survival after resection was greater for patients with tumor SUV values of less than 4 (56 mo vs. 19 mo).[15] Patients with complete metabolic response following radiation therapy were reported to have median survivals of 31 months versus 11 months.[17]

FDG-PET may be more sensitive and specific than computed tomography scan in assessing response to induction therapy. Optimal timing imaging remains to be defined; however, one study suggests that greater sensitivity and specificity of FDG-PET is achieved if repeat imaging is delayed until 30 days after radiation therapy.[16]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients withnon-small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Lester JF, MacBeth FR, Coles B: Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small-cell lung cancer: a Cochrane Review. Int J Radiat Oncol Biol Phys 63 (3): 690-4, 2005. [PUBMED Abstract]
2. Pöttgen C, Eberhardt W, Grannass A, et al.: Prophylactic cranial irradiation in operable stage IIIA non small-cell lung cancer treated with neoadjuvant chemoradiotherapy: results from a German multicenter randomized trial. J Clin Oncol 25 (31): 4987-92, 2007. [PUBMED Abstract]
3. Chemotherapy for non-small cell lung cancer. Non-small Cell Lung Cancer Collaborative Group. Cochrane Database Syst Rev (2): CD002139, 2000. [PUBMED Abstract]
4. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group. BMJ 311 (7010): 899-909, 1995. [PUBMED Abstract]
5. Spiro SG, Rudd RM, Souhami RL, et al.: Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life. Thorax 59 (10): 828-36, 2004. [PUBMED Abstract]
6. Clegg A, Scott DA, Hewitson P, et al.: Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review. Thorax 57 (1): 20-8, 2002. [PUBMED Abstract]
7. Pao W, Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol 12 (2): 175-80, 2011. [PUBMED Abstract]
8. Curran WJ, Scott CB, Langer CJ, et al.: Long-term benefit is observed in a phase III comparison of sequential vs concurrent chemo-radiation for patients with unresected stage III nsclc: RTOG 9410. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2499, 2003.
9. Fournel P, Robinet G, Thomas P, et al.: Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95-01 Study. J Clin Oncol 23 (25): 5910-7, 2005. [PUBMED Abstract]
10. Zatloukal P, Petruzelka L, Zemanova M, et al.: Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer 46 (1): 87-98, 2004. [PUBMED Abstract]
11. Rowell NP, O'rourke NP: Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev (4): CD002140, 2004. [PUBMED Abstract]
12. Cerfolio RJ, Bryant AS, Winokur TS, et al.: Repeat FDG-PET after neoadjuvant therapy is a predictor of pathologic response in patients with non-small cell lung cancer. Ann Thorac Surg 78 (6): 1903-9; discussion 1909, 2004. [PUBMED Abstract]
13. Pöttgen C, Levegrün S, Theegarten D, et al.: Value of 18F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography in non-small-cell lung cancer for prediction of pathologic response and times to relapse after neoadjuvant chemoradiotherapy. Clin Cancer Res 12 (1): 97-106, 2006. [PUBMED Abstract]
14. Eschmann SM, Friedel G, Paulsen F, et al.: 18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer. Eur J Nucl Med Mol Imaging 34 (4): 463-71, 2007. [PUBMED Abstract]
15. Hellwig D, Graeter TP, Ukena D, et al.: Value of F-18-fluorodeoxyglucose positron emission tomography after induction therapy of locally advanced bronchogenic carcinoma. J Thorac Cardiovasc Surg 128 (6): 892-9, 2004. [PUBMED Abstract]
16. Cerfolio RJ, Bryant AS: When is it best to repeat a 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan on patients with non-small cell lung cancer who have received neoadjuvant chemoradiotherapy? Ann Thorac Surg 84 (4): 1092-7, 2007. [PUBMED Abstract]
17. Mac Manus MP, Hicks RJ, Matthews JP, et al.: Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer. J Clin Oncol 21 (7): 1285-92, 2003. [PUBMED Abstract]