Review of the treatment of metastatic non small cell lung carcinoma: A practical approach

Table 1 Efficacy (progression-free survival) outcomes of trials in the maintenance setting in patients with non small cell lung carcinoma

Trial	Treatment	n	Median PFS (mo)	HR
AVAiL[31]	Placebo	41	3.2	NR
	Bevacizumab 7.5 mg/kg	174	4.6
	Bevacizumab 15 mg/kg	162	4.6
ATLAS[32]	Bevacizumab + erlotinib	370	4.76	0.722
	Bevacizumab + placebo	373	3.75	P = 0.0012
SATURN[33]	Erlotinib	437	NR	0.71
	Placebo	447	NR	P < 0.0001
JMEN[30]	Pemetrexed	441	4.0	0.5
	Placebo	222	2.0	P < 0.0001

PFS: Progression-free survival; HR: Hazard ratio.

Table 2 Efficacy data in the second-line setting

Outcome	Erlotinib[41] (150 mg daily)	Docetaxel[38-40,46](75 mg/m2 , every 3 wk)	Pemetrexed[40] (500 mg/m2 , every 3 wk)
RR (%)	8.9	6.7-8.8	9.1
Median duration of response (mo)	7.9	5.3-9.1	4.6
Median PFS (mo)	2.2	2.7-6	2.9
Median OS (mo)	6.7	5.7-7.9	8.3
1-year survival (%)	31	30-37	30
2-year survival (%)	13	0	0
Median OS (mo) in PS 0/1 patients with one prior regimen	9.4	9.1	9.4

PFS: Progression-free survival; OS: Overall survival; PS: Performance status

Table 3 Selected trials of erlotinib and bevacizumab

Study	Phase	n	Eligibility	Regimen	Line of therapy	Primary endpoint
PASSPORT (AVF3752g)	II	110	Previously treated or untreated non-squamous NSCLC with treated CNS metastases	Chemo or erlotinib followed by bev	First/second	Grade ≥ 2 symptomatic CNS haemorrhage
BRAIN (AVF21823)	II	115	Stage IV non-squamous NSCLC with asymptomatic brain metastases in first and second line	First line: bev + carbo/pac	First/second	PFS
				Second line: bev + erlotinib
EAGLES	II	78	Patients aged > 70 yr without important comorbidities	Bev + gem or bev + gem/cis	First	PFS at 6 mo
ML21896	II	~250	Patients aged ≥ 65 yr with advanced metastatic or recurrent non-squamous NSCLC	Bev + pem or bev + pem/carbo	First	Proof of non-inferiority of bev + pem
BRIDGE (AVF2744g)	I/II	40	Previously untreated squamous NSCLC	Bev + carbo/pac	First	Grade ≥ 3 pulmonary haemorrhage
ABIGAIL (BO21015)	II	~300	Locally advanced, metastatic or recurrent non-squamous NSCLC	Bev + carbo/gem or carbo/pac	First	Correlation of biomarkers with response
MIMEB (ML21803)	II	40	Histologically confirmed advanced non-squamous NSCLC stage IIIB/IV	Bev + erlotinib	First	Evaluate accuracy of FDG-/FLT-PET and DCE-MRI for early prediction of non-progression
EURTAC	III	146	EGFR mutation-positive NSCLC	Erlotinib	First	PFS in patients with
SATURN (BO18192)	III	1949	Previously untreated advanced NSCLC	Erlotinib	First	PFS in all patients and in patients with EGFR IHC+ tumours
RADIANT		945	Advanced NSCLC	Erlotinib vs placebo	Adjuvant	DFS
FASTACT-2	III	450	Asian patients with previously untreated advanced NSCLC	Erlotinib + chemo vs placebo + chemo	First line	PFS
ATLAS (AVF3671f)	III	1150	Previously untreated advanced NSCLC	Bev + carbo/pac, gem/cis or carbo/doc)	First line maintenance	PFS
				Non-progressing patients randomized (1:1) to bev + erlotinib or bev + placebo
TARGET	II	428	EGFR mutation-positive NSCLC	Erlotinib	First	PFS
TORCH	III	900	Previously untreated advanced NSCLC	First-line erlotinib second-line gem/cis vs first-line gem/cis second-line erlotinib	First/second	OS

NSCLC: Non-small cell lung cancer; CNS: Central nervous system; bev: Bevacizumab; carbo: Carboplatin; pac: Paclitaxel; PFS: Progression-free survival; gem: Gemcitabine; cis: Cisplatin; pem: Pemetrexed; FDG: [18F]-2-fluoro-deoxy-D-glucose; FLT: F-fluorodeoxythymidine; PET: Positron emission tomography; DCE-MRI: Dynamic contrast-enhanced magnetic resonance imaging; EGFR: Epidermal growth factor receptor; IHC: Immunohistochemistry; DFS: Disease-free survival; chemo: Chemotherapy; doc: Docetaxel; OS: Overall survival.