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CORRIGENDUM
Metastatic non-small cell lung cancer: ESMO Clinical
Practice Guidelines for diagnosis, treatment and
follow-up
D. Planchard, S. Popat, K. Kerr, S. Novello, E. F. Smit, C. Faivre-Finn, T. S. Mok, M. Reck, P. E. Van Schil,
M. D. Hellmann & S. Peters, on behalf of the ESMO Guidelines Committee
Ann Oncol 2018; 29: iv192–iv237 (doi:10.1093/annonc/mdy275)
The following corrections are made:
In the section “Management of advanced/metastatic NSCLC, First-line treatment of EGFR- and ALK-negative NSCLC disease,
regardless of PD-L1 status”
1. In KEYNOTE-189, patients with metastatic non-squamous NSCLC, PS 0-1, without sensitising EGFR or ALK mutations, were rand-
omised to receive pemetrexed and a platinum-based ChT plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles,
followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy [96].
Is replaced with:
In KEYNOTE-189, patients with metastatic non-squamous NSCLC, PS 0-1, without sensitising EGFR or ALK mutations, were rando-
mised to receive pemetrexed and cisplatin or carboplatin plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles,
followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy [96].
2. Recently, the combination of carboplatin or cisplatin with pemetrexed and atezolizumab has been shown, in the context of the
IMpower132 trial, to be superior to the ChT doublet.
Is replaced with:
Recently, the combination of carboplatin or cisplatin with pemetrexed and atezolizumab followed by maintenance pemetrexed and
atezolizumab has been shown, in the context of the IMpower132 trial, to be superior to the ChT doublet followed by maintenance
pemetrexed.
3. Atezolizumab was studied in patients with metastatic squamous NSCLC in the IMpower131 study. Patients were randomised to ate-
zolizumab/carboplatin/paclitaxel, atezolizumab/carboplatin/nab-P or carboplatin/nab-P (nab-PC) [100]. Atezolizumab/carboplatin/
nab-P had improved PFS compared with nab-PC (HR 0.715, P=0.0001), but no improvement in OS was seen at the first interim ana-
lysis (mOS 14 versus 13.9 months). More mature data are needed to evaluate long-term benefit of the strategy; with the use of atezoli-
zumab with nab-PC today representing an option in patients with metastatic squamous NSCLC [I, B; not EMA-approved].
Is replaced with:
Atezolizumab was studied in patients with metastatic squamous NSCLC in the IMpower131 study. Patients were randomised to atezo-
lizumab/carboplatin/paclitaxel, atezolizumab/carboplatin/nab-P or carboplatin/nab-P [100]. Atezolizumab/carboplatin/nab-P had
improved PFS compared with carboplatin/nab-P (HR 0.715, P=0.0001), but no improvement in OS was seen at the first interim ana-
lysis (mOS 14 versus 13.9 months). More mature data are needed to evaluate the long-term benefit of the strategy; with the use of ate-
zolizumab with carboplatin and nab-P today representing an option in patients with metastatic squamous NSCLC [I, B; not EMA-
approved].
V
CThe Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oup.com.
Annals of Oncology 30: 863–870, 2019
doi:10.1093/annonc/mdy474
Published online 30 January 2019
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In the section “First-line treatment of NSCLC without actionable oncogenic driver, with contraindications to use of
immunotherapy”
• The nab-PC regimen has been shown in a large phase III trial to have a significantly higher ORR compared with solvent-based pacli-
taxel/carboplatin (sb-PC), and less neurotoxicity [I, B] [113]. The benefits were observed in both SCC and non-SCC (NSCC), with a
larger impact on response in SCC. For this reason, the nab-PC regimen could be considered a chemotherapeutic option in advanced
NSCLC patients, particularly in patients with greater risk of neurotoxicity, pre-existing hypersensitivity to paclitaxel or contraindica-
tions for standard paclitaxel premedication [I, B].
Is replaced with:
• The carboplatin/nab-P regimen has been shown in a large phase III trial to have a significantly higher ORR compared with solvent-
based paclitaxel/carboplatin (sb-PC), and less neurotoxicity [I, B] [113]. The benefits were observed in both SCC and non-SCC
(NSCC), with a larger impact on response in SCC. For this reason, the carboplatin/nab-P regimen could be considered a chemothera-
peutic option in advanced NSCLC patients, particularly in patients with greater risk of neurotoxicity, pre-existing hypersensitivity to
paclitaxel or contraindications for standard paclitaxel premedication [I, B].
In “Table 4. Summary of recommendations”
1. • The nab-PC regimen could be considered a chemotherapeutic option in advanced NSCLC patients, particularly in patients with
greater risk of neurotoxicity, preexisting hypersensitivity to paclitaxel or contraindications for standard paclitaxel premedication [I, B]
Is replaced with:
• The carboplatin/nab-P regimen could be considered a chemotherapeutic option in advanced NSCLC patients, particularly in patients with
greater risk of neurotoxicity, preexisting hypersensitivity to paclitaxel or contraindications for standard paclitaxel premedication [I, B]
2. • The use of atezolizumab with nab-PC today represents an option in patients with metastatic squamous NSCLC [I, B; not
EMA-approved]
Is replaced with:
• The use of atezolizumab with carboplatin and nab-P today represents an option in patients with metastatic squamous NSCLC [I, B;
not EMA-approved]
A new acronym is defined:
nab-P, albumin-bound paclitaxel.
Figures
In “Figure 1. Treatment algorithm for stage IV SCC”
The following changes apply as shown in the updated version below.
1. PD-L1 <50%
Is replaced with:
Any expression of PD-L1
2. Pembrolizumab þcarboplatin/paclitaxel or nab-PC (4 cycles), followed by pembrolizumab [I, A]
c
Is replaced with:
Pembrolizumab þcarboplatin/paclitaxel or carboplatin/nab-P (4 cycles), followed by pembrolizumab [I, A]
c
3. Atezolizumab + nab-PC (4-6 cycles), followed by atezolizumab [II, B]
c
Is replaced with:
Atezolizumab + carboplatin/nab-P (4-6 cycles), followed by atezolizumab [II, B]
c
4. Platinum-based ChT (see first-line treatment for PD-L1 <50%, PS 0-1)
Is replaced with:
Platinum-based ChT (see first-line treatment without IO)
5. 4-6 cycles Carboplatin-based doublets
Is replaced with:
4-6 cycles Carboplatin-based ChT
Corrigendum Annals of Oncology
864 | Planchard et al. Volume 30 | Issue 5 | 2019
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New acronyms are defined:
IO, immuno-oncology; nab-P, albumin-bound paclitaxel.
In “Figure 2. Treatment algorithm for stage IV NSCC, molecular tests negative(ALK/BRAF/EGFR/ROS1)”
The following changes apply as shown in the updated version below.
1. PD-L1 expression
a
has been added to show the options between “PD-L1 50%” and “Any expression of PD-L1”
2. Pembrolizumab/pemetrexed and platinum-based ChT (4 cycles), followed by pembrolizumab [I, A; MCBS 4]
Is replaced with:
Pembrolizumab/pemetrexed and platinum-based ChT (4 cycles), followed by pembrolizumab/pemetrexed [I, A; MCBS 4]
3. Atezolizumab/pemetrexed/platinum-based ChT (4-6 cycles), followed by atezolizumab [I, B]
b
Is replaced with:
Atezolizumab/pemetrexed and platinum-based ChT (4-6 cycles), followed by atezolizumab/pemetrexed [I, B]
b
4. 4-6 cycles
Is replaced with:
4-6 cycles Platinum-based ChT
5. nab-PC [I, B]
Is replaced with:
carboplatin/nab-P [I, B]
6. 4-6 cycles Carboplatin-based doublets
Is replaced with:
4-6 cycles Carboplatin-based ChT
7. For the following first-line treatment combinations, links have been added to show the treatment options in case of disease progres-
sion: pembrolizumab/pemetrexed and platinum-based ChT (4 cycles), followed by pembrolizumab/pemetrexed; atezolizumab/peme-
trexed and platinum-based ChT (4-6 cycles), followed by atezolizumab/pemetrexed; atezolizumab/bevacizumab with carboplatin and
paclitaxel (4-6 cycles), followed by atezolizumab/bevacizumab.
A new acronym is defined:
nab-P, albumin-bound paclitaxel.
In “Figure 3. Treatment algorithm for stage IV NSCC, molecular tests positive (ALK/BRAF/EGFR/ROS1)”
The following changes apply as shown in the updated version below.
Osimertinib [I, A]
b
Is replaced with:
Osimertinib [I, A; MCBS 4].
In “Figure 4. Treatment algorithm for stage IV lung carcinoma with EGFR-activating mutation”
The following changes apply as shown in the updated version below.
Carbolatin/paclitaxel/bevacizumab/atezolizumab [III, A]
b
Is replaced with:
Carboplatin/paclitaxel/bevacizumab/atezolizumab [III, A]
b
In “Figure 5. Treatment algorithm for stage IV lung carcinoma with ALK translocation”
The following changes apply as shown in the updated version below.
Carbolatin/paclitaxel/bevacizumab/atezolizumab [III, B]
a
Is replaced with:
Carboplatin/paclitaxel/bevacizumab/atezolizumab [III, B]
a
Annals of Oncology Corrigendum
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Stage IV SCC
Never or former light
smoker (< 15 pack-years)a
PD-L1 expressionb
PD-L1 ≥ 50%
High TMB
(≥ 10 mutations/Mb)
Any expression of PD-L1
PS 3-4PS 0-1
Molecular test
Targeted
therapy
Positive Negative
Follow recommended
treatment in
function of PD-L1
expression level
Nivolumab [I, A, MCBS 5]
Atezolizumab [I, A; MCBS 5]
Pembrolizumab if PD-L1 > 1% [I, A; MCBS 5]
Docetaxel [I, B]
Ramucirumab/docetaxel [I, B; MCBS 1]
Erlotinib [II, C]
Afatinib [I, C; MCBS 2]
PS 0-1
Pembrolizumab
[I, A; MCBS 5]
Nivolumab/ipilimumab
[I, A]c
PS 0-1
Platinum–based ChT
(see fi rst-line treatment without IO)
Pembrolizumab
+ carboplatin/
paclitaxel or
carboplatin/nab-P
(4 cycles), followed
by pembrolizumab
[I, A]c
Atezolizumab
+ carboplatin/
nab-P (4-6 cycles),
followed by
atezolizumab
[I, B]c
4-6 cycles
Platinum–based ChT:
Cisplatin/gemcitabine [I, A]
Cisplatin/docetaxel [I, A]
Cisplatin/paclitaxel [I, A]
Cisplatin/vinorelbine [I, A]
Carboplatin/gemcitabine [I, A]
Carboplatin/docetaxel [I, A]
Carboplatin/paclitaxel [I, A]
Carboplatin/vinorelbine [I, A]
Carboplatin/nab-P [I, B]
4-6 cycles
Carboplatin-based ChT:
< 70 years and PS 2 [II, A]
≥ 70 years and PS 0-2 [I, A]
Single-agent ChT:
Gemcitabine, vinorelbine or
docetaxel [I, B]
BSC [II, B]
BSC
Disease progression Disease progression
PS 0-2 PS 3-4
< 70 years and PS 2
or
Selected ≥ 70 years and PS 0-2
Figure 1. Treatment algorithm for stage IV SCC.
a
Molecular testing is not recommended in SCC, except in those rare circumstances when SCC is found in a never-, long-time ex- or light-smoker (<15 pack-years).
b
In absence of contraindications and conditioned by the registration and accessibility of anti-PD-(L)1 combinations with platinum-based ChT, this strategy will be preferred to plat-
inum-based ChT in patients with PS 0-1 and PD-L1 <50%. Alternatively, if TMB can accurately be evaluated, and conditioned by the registration and accessibility, nivolumab plus
ipilimumab should be preferred to platinum-based standard ChT in patients with NSCLC with a high TMB.
c
Not EMA-approved.
ALK, anaplastic lymphoma kinase; BSC, best supportive care; ChT, chemotherapy; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; IO, immuno-oncology;
Mb, megabase; MCBS, ESMOMagnitude of Clinical Benefit Scale; nab-P, albumin-bound paclitaxel; NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein 1; PD-
L1, programmed death-ligand 1; PS, performance status; SCC, squamous cell carcinoma; TMB, tumour mutation burden.
Corrigendum Annals of Oncology
866 | Planchard et al. Volume 30 | Issue 5 | 2019
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PD-L1 ≥ 50%
High TMB
(≥ 10 mutations/Mb)
Partial response or stable disease
Any expression of PD-L1
PD-L1 expressiona
PS 0-1
Pembrolizumab
[I, A; MCBS 5]
Stage IV NSCC: Molecular tests negative ( )
BSC [II, B]
BSC
4-6 cycles
Carboplatin-based ChT:
< 70 years and PS 2 [II, A]
≥ 70 years and PS 0-2 [I, A]
Single-agent ChT:
Gemcitabine, vinorelbine,
docetaxel [I, B]
or pemetrexed [III, B]
Nivolumab [I, A, MCBS 5]
Atezolizumab [I, A; MCBS 5]
Pembrolizumab if PD-L1 > 1% [I, A; MCBS 5]
Docetaxel [I, B]
Pemetrexed [I, B]
Ramucirumab/docetaxel [I, B; MCBS 1]
Nintedanib/docetaxel [II, B]
Erlotinib [II, C]
PS 0-1
Platinum–based ChT
(see fi rst-line treatment without IO)
Pembrolizumab/
pemetrexed and
platinum-based
ChT (4 cycles),
followed by
pembrolizumab/
pemetrexed
[I, A; MCBS 4]
Nivolumab/
ipilimumab
[I, A]b
Atezolizumab/
bevacizumab
with carboplatin
and paclitaxel
(4-6 cycles),
followed by
atezolizumab
/bevacizumab
[I, A]b
4-6 cycles
Platinum–based ChT:
Cisplatin/gemcitabine [I, A]
Cisplatin/docetaxel [I, A]
Cisplatin/paclitaxel [I, A]
Cisplatin/vinorelbine [I, A]
Carboplatin/gemcitabine [I, A]
Carboplatin/docetaxel [I, A]
Carboplatin/paclitaxel [I, A]
Carboplatin/vinorelbine [I, A]
Cisplatin/pemetrexed [II, A]
Carboplatin/pemetrexed [II, B]
Carboplatin/nab-P [I, B]
+/- bevacizumab [I, A with carboplatin/
palitaxel, otherwise III, B]
Maintenance treatment:
Pemetrexed (continuation) [I, A]
Gemcitabine (continuation) [I, B]
Pemetrexed (switch) [I, B]
+/- bevacizumab (if given before)
PS 0-1
Disease progression
< 70 years and PS 2
or
Selected ≥ 70 years and PS 0-2
PS 3-4
PS 0-2 PS 3-4
Disease progression
Atezolizumab/
pemetrexed and
platinum-based
ChT (4-6 cycles),
followed by
atezolizumab/
pemetrexed [I, B]b
Figure 2. Treatment algorithm for stage IV NSCC, molecular tests negative (ALK/BRAF/EGFR/ROS1).
a
In absence of contraindications and conditioned by the registration and accessibility of anti-PD-(L)1 combinations with platinum-based ChT, this strategy will be preferred to plat-
inum-based ChT in patients with PS 0-1 and PD-L1 <50%. Alternatively, if TMB can accurately be evaluated, and conditioned by the registration and accessibility, nivolumab plus
ipilimumab should be preferred to platinum-based standard ChT in patients with NSCLC with a high TMB.
b
Not EMA-approved.
ALK, anaplastic lymphoma kinase; BSC, best supportive care; ChT, chemotherapy; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; IO, immuno-oncology;
Mb, megabase; MCBS, ESMO-Magnitude of Clinical Benefit Scale; nab-P, albumin-bound paclitaxel; NSCC, non-squamous cell carcinoma; NSCLC, non-small cell lung cancer; PD-1,
programmed cell death protein 1; PD-L1, programmed death-ligand 1; PS, performance status; TMB, tumour mutation burden.
Annals of Oncology Corrigendum
Volume 30 | Issue 5 | 2019 doi:10.1093/annonc/mdy474 | 867
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Figure 3. Treatment algorithm for stage IV NSCC, molecular tests positive (ALK/BRAF/EGFR/ROS1).
a
MCBS score for the combination of bevacizumab with gefitinib or erlotinib.
b
Not EMA-approved.
ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; MCBS, ESMO-Magnitude of Clinical Benefit Scale; NSCC, non-squa-
mous cell carcinoma.
Corrigendum Annals of Oncology
868 | Planchard et al. Volume 30 | Issue 5 | 2019
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Figure 4. Treatment algorithm for stage IV lung carcinoma with EGFR-activating mutation.
b
Not EMA-approved.
cfDNA, cell-free DNA; ChT, chemotherapy; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; MCBS, ESMO-Magnitude of Clinical Benefit Scale; PS, per-
formance status; RT, radiotherapy.
Annals of Oncology Corrigendum
Volume 30 | Issue 5 | 2019 doi:10.1093/annonc/mdy474 | 869
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Figure 5. Treatment algorithm for stage IV lung carcinoma with ALK translocation.
a
Not EMA-approved.
ALK, anaplastic lymphoma kinase; ChT, chemotherapy; EMA, European Medicines Agency; MCBS, ESMO-Magnitude of Clinical Benefit Scale; RT, radiotherapy; TKI, tyrosine kinase
inhibitor.
Corrigendum Annals of Oncology
870 | Planchard et al. Volume 30 | Issue 5 | 2019
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