Supplementary Table 2 | Drug rechallenge following progression on therapy
Number of patients
Class
Agent(s)
Setting
Study type
Original
cohort
Monoclonal
antibody/EGFR
inhibitor
Cetuximab +
irinotecanbased
chemotherapy
Tyrosine
kinase/EGFR
inhibitor
Erlotinib*
Tyrosine
kinase/EGFR
inhibitor
Gefitinib
Tyrosine
kinase/EGFR
inhibitor
Gefitinib
Tyrosine
kinase/EGFR
inhibitor
Gefitinib
Tyrosine
kinase/EGFR
inhibitor
Gefitinib
Tyrosine
kinase/EGFR
inhibitor
Imatinib
Colorectal
carcinoma,
K-ras
wildtype
Advanced
non-small
cell lung
carcinoma
Advanced
non-small
cell lung
carcinoma
Advanced
non-small
cell lung
carcinoma
Advanced
non-small
cell lung
carcinoma
Advanced
non-small
cell lung
carcinoma
Gastrointesti
nal stromal
tumour
Rechallenged,
evaluable for
response
Median
interval
between
initial
therapy and
rechallenge
(months)
Intervening
therapy(s)
Initial response
Rechallenge response
PFS or TTP (months)
%ORR
%SD
%ORR
%SD
Initial
Rechallenge
OS from
start of
rechallenge
(months)
89.7
10.3
53.8
35.9
10
6.6
__
Santini 20121
Reference
Prospective
multicentre
phase II
39
39
6
All patients
(bevacizumab ±
5-FU, oxaliplatin
or irinotecan)
Retrospective
14
13§
9.5
All patients
(platinum-based
chemotherapy)
100
0
36
50
12.5
6.5
__
Becker 20112
Retrospective
6
5
N/A
All patients
(cytotoxic
chemotherapy)
100
0
20
60
N/A
(Range 0.6 to
7.8)
__
Yokouchi 20073
Retrospective
multicentre
20
20
7.1
All patients (1-3
cytotoxic
agents)
80
20
25
40
10.8
(duration of
treatment)
3.9 (duration
of treatment)
10.0
Tomizawa 20104
Prospective
phase II
16
15
(50%
≤6 months)
All patients
(cytotoxic
chemotherapy)
100
0
0
46.7
N/A
2.5
14.7
Asahina 20105
Prospective
phase II
23
20
7.0
All patients (≥1
cytotoxic
regimens)
43.5‡
56.5‡
21.7
43.5
9.1
3.4
11.3
Oh 20126
Retrospective
14
14
N/A
All patients
(sunitinib)
N/A
N/A
0
21
N/A
N/A
22 vs.
4 BSC
Sawaki 20107
Tyrosine
kinase/EGFR
inhibitor
Imatinib
Gastrointesti
nal stromal
tumour
Retrospective
multicentre
223
40
9.2‡
All patients
(sunitinib)
N/A
Tyrosine
kinase/EGFR
inhibitor
Imatinib
Gastrointesti
nal stromal
tumour
Prospective,
single centre,
phase III
81
41
N/A
All (sunitinib),
40% ≥3 prior
TKIs
N/A
N/A
6
19
DCR 12 weeks 32%
(vs. 5% placebo)
25.5‡
2.9
7.5
Italiano 20128
N/A
1.8 vs. 0.9
placebo
8.2 (vs. 7.5
placebo)
Kang 20139
All patients (1-4
therapies, for
Tyrosine
Metastatic
example,
kinase/VEGFR
Sorafenib
renal cell
Retrospective 12
8
7.6
18||
63.6||
0||
72.7||
5.7
5.4
__
Nozawa 201210
sunitinib,
inhibitor
carcinoma
everolimus,
thalidomide)
All patients
Tyrosine kinase
Metastatic
(sorafenib, ±
Retrospective
/ VEGFR
Sunitinib
renal cell
23
23#
6.7
bevacizumab, ±
65
29
21
71
13.7
7.2
__
Zama 201011
multicentre
inhibitor
carcinoma
mTOR inhibitor,
other)
All
Tyrosine kinase
Metastatic
(temsirolimus,
/ VEGFR
Sunitinib
renal cell
Retrospective 13
13**
13
75
25
15
77
21
6.9
__
Grünwald 201112
everolimus, +4
inhibitor
carcinoma
sorafenib)
Original cohort = patients receiving initial therapy, rechallenged with a drug combination not reflective of ‘true’ rechallenge, or sum of evaluable+non-evaluable patients. Rechallenge patient numbers reflect those patients receiving both initial
and rechallenge therapy that were evaluable for response. Other cases are noted. When appropriate weeks converted into months: 1 week = 0.229,984 months, days converted into months: 1 day = 0.0328,549 months. *8 patients received
erlotinib to erlotinib, 3 pts sorafenib+erlotinib to erlotinib, 2 pts erlotinib to cetuximab+erlotinib. PFS calculation includes a 14th patient receiving gefitinib to erlotinib. ‡Data based on original cohort of patients/intent to treat population. Patients
received initial therapy, but not all were rechallenged (due to lack of PD or patients not evaluable for response). §Patient received initial gefitinib (not true rechallenge, however provided data includes this patient). ||Response rates recalculated
using data from 8 evaluable patients rechallenged following PD on sorafenib. #Includes 2 patients with increased dose at rechallenge. **Data includes 2 patients that discontinued initial sunitinib early, prior to PD. Abbreviations: BSC, best
supportive care; ORR, overall response rate = PR (partial response) + CR (complete response); PD, progressive disease; PFS, progression-free survival; pts, patients; SD, stable disease; TTP, time to progression.
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