Lung cancer

Are three chemotherapy agents better than two chemotherapy agents for treatment of stage IV inoperable NSCLC?

From Cancer Guidelines Wiki


The majority of patients treated with NSCLC have stage IV disease, with common sites of metastases including lymph nodes, the pleura, liver, adrenal glands, bone and brain. Consequently, systemic therapy has been the mainstay of treatment attempting to control overall disease. A historical summary of the evolution of systemic drug treatment for stage IV NSCLC can be found here The focus of the following question will be based on the evidence in support of the old and new practice paradigms for stage IV NSCLC. Empirical therapy refers to therapy given to all fit patients deemed suitable without any particular restrictions.

Triplet regimens versus doublet regimens

Delbaldo et al also examined the effectiveness of three-drug combination chemotherapy compared with two-drug combination chemotherapy.[1] This study evaluated 4814 patients from 28 RCTs.Adding a third drug to a doublet regimen was associated with a significantly increased response rate (RR) (OR, 0.66; 95%CI, 0.58-0.75; p <.001).[1] The absolute benefit was 8%, which corresponds to an increase in tumour RR from 23% (doublet regimen) to 31% (triplet regimen).[1] There was no difference in RR whether the doublet regimens contained older or newer (3G) drugs (p=0.33). Adding a third drug to a doublet regimen did not improve one-year survival (OR, 1.01;95% CI, 0.85-1.21; P=0.88) and there was no significant difference according to the type of control regimens used (older drugs versus newer (3G) drugs) for both one-year survival rate (p =.28) and median survival (p =.36).[1] However, grade ¾ toxicity was more common in triplet regimens than in doublet regimens with ORs ranging from 1.4 to 2.9,except for neurological, renal, auditory and gastrointestinal toxic effects.[1]

Evidence summary and recommendations

Evidence summary Level References
Triplet chemotherapy regimens are associated with higher response rate, but no improvement in survival.

Last reviewed September 2017

I [1]
Triplet chemotherapy regimens are associated with greater grade 3 /4 toxicities.

Last reviewed September 2017

I [2]
Evidence-based recommendationQuestion mark transparent.png Grade
Triplet chemotherapy regimens are not recommended, as benefit in response rate does not outweigh extra toxicity.

Last reviewed September 2017


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  1. 1.0 1.1 1.2 1.3 1.4 1.5 Delbaldo C, Michiels S, Rolland E, Syz N, Soria JC, Le Chevalier T, et al. Second or third additional chemotherapy drug for non-small cell lung cancer in patients with advanced disease. Cochrane Database Syst Rev 2007 Oct 17;(4):CD004569 Available from:
  2. Baggstrom MQ, Stinchcombe TE, Fried DB, Poole C, Hensing TA, Socinski MA. Third-generation chemotherapy agents in the treatment of advanced non-small cell lung cancer: a meta-analysis. J Thorac Oncol 2007 Sep;2(9):845-53 Available from:

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Further resources

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