Radiol Oncol 2021; 55(4): 482-490. doi: 10.2478/raon-2021-0044
482
research article
Clinical outcomes in stage III non-small cell 
lung cancer patients treated with durvalumab 
after sequential or concurrent platinum-
based chemoradiotherapy – single institute 
experience
Martina Vrankar1,2, Karmen Stanic1,2, Stasa Jelercic1, Eva Ciric1, Ana Lina Vodusek1, 
Jasna But-Hadzic1,2 
1 Institute of Oncology Ljubljana, Department of Radiotherapy, Ljubljana, Slovenia
2 University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia
Radiol Oncol 2021; 55(4): 482-490.
Received 19 August 2021
Accepted 7 October 2021
Correspondence to: Jasna But-Hadzic, M.D., Ph.D., Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia. 
E-mail: jbut@onko-i.si; 
Disclosure: No potential conflicts of interest were disclosed. 
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Background. Chemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for 
unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is 
scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the us-
age of gemcitabine.
Patients and methods. We retrospectively analysed unresectable stage III NSCLC patients who were treated with 
durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treat-
ment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding 
baseline characteristic of patients.
Results. Eighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with 
squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients 
received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) 
received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during con-
current treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12–99 days) 
from the end of the RT and were treated with the median of 10.8 (range 0.5–12 months) months. Forty-one patients 
(48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to 
the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 
24-month PFS were 71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–58.9%). With the median follow-up time of 23 
months (range 2–35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% 
(95% CI: 79.5–93.9%) and 68.6% (95% CI: 57.2–79.9%).
Conclusions. Our survival data are comparable with published research as well as with recently published real-world 
reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was 
efficient and well tolerated.
Key words: non-small cell lung cancer; stage III; chemoradiotherapy; durvalumab 
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Vrankar M et al. / Outcome of lung cancer patients after durvalumab treatment 483
Introduction
In the last few years, standard treatment of un-
resectable stage III non-small cell lung cancer 
(NSCLC) changed considerably after the publica-
tion of improved survival results with maintenance 
12-month treatment with Programmed Death 
Ligand 1 (PD-L1) antibody durvalumab following 
standard concurrent chemoradiotherapy (ChT-
RT).1-3 In the PACIFIC trial, the median progres-
sion-free survival (PFS) from randomization was 
17.2 months in durvalumab arm versus 5.6 months 
in placebo arm, while median overall survival (OS) 
was 47.5 months vs. 29.1 months, respectively. 
Reported 48-month OS rates were 49.6% for dur-
valumab vs. 36.3% for placebo.4 However, survival 
data for stage III NSCLC patients treated with dur-
valumab after ChT-RT in every day routine clini-
cal practice is scarce, as well as the survival data of 
patients treated with sequential ChT-RT followed 
by durvalumab. Patients with unresectable stage 
III NSCLC are highly heterogeneous regarding 
age, performance status (PS) and comorbidity and 
high proportion of them are not fit for concurrent 
ChT-RT.5,6 Here we present single centre survival 
and safety results for the treatment of unresectable 
stage III NSCLC patients with sequential or con-
current ChT-RT and maintenance durvalumab. 
Patients and methods 
Patients and treatment
We retrospectively analysed unresectable stage III 
NSCLC patients (according to the 8th TNM clas-
sification) who were considered for maintenance 
treatment with durvalumab (intention to treat 
population, ITT) after radical ChT-RT and com-
pleted treatment until December 2020.7 First 61 
patients were included in early access program 
(EAP) which started in December 2017 and ended 
in September 2019 when reimbursement was in-
troduced. Afterwards patients were treated with 
durvalumab as a standard of care. During EAP, pa-
tients were treated with durvalumab after at least 
stable disease with ChT-RT was achieved regard-
less of PD-L1 expression level, but from September 
2019, during standard of care treatment, only 
patients with PD-L1 ≥ 1% received adjuvant dur-
valumab according to European Medicines Agency 
(EMA) registration.
Before treatment, patients underwent a physi-
cal examination, computed tomography (CT) 
of the chest, abdomen and head as well as the 
18F-fluorodeoxyglucose positron emission tomog-
raphy/computed tomography (18F-FDG PET/CT) 
and brain magnetic resonance imaging (MRI) 
when indicated. All patients had histologically 
or cytologically confirmed NSCLC from primary 
tumour or regional lymph nodes, N stage mostly 
confirmed with endobronchial ultrasound (EBUS). 
PD-L1 immunohistochemistry was evaluated with 
a rabbit monoclonal antibody SP263 as part of the 
Ventana PD-L1 SP263 assay (Ventana/Roche, USA) 
on an automated platform (Benchmark, Ventana/
Roche, USA). According to our institutional clini-
cal practice most patients started treatment with 
platinum based ChT combined with gemcitabine 
or pemetrexed and continued with platinum based 
ChT with the addition of etoposide or pemetrexed 
concurrently with RT. The prescribed radiation 
dose ranged from 54 Gray (Gy) to 66 Gy in 2 Gy 
daily fractions. Treatment was planned with Three-
Dimensional Conformal Radiotherapy (3D-CRT) or 
Volumetric Modulated Arc Therapy (VMAT) with 
four-dimensional CT (4D CT) simulation in case 
of extensive target motion. Daily cone-beam CT 
was used for set-up correction. After completion of 
ChT-RT patients were evaluated with CT scan of 
the chest and abdomen, and when indicated, CT 
of the brain. Patients without progression and with 
resolved toxic effects of previous treatment started 
durvalumab within 3 months after ChT-RT for 12 
months until progression or until unacceptable 
toxicity. Evaluation thoracic CT was done 6 and 12 
months after durvalumab introduction and when 
clinically indicated. 
Statistical analysis
Baseline characteristics of patients, including age, 
gender, pathological features, TNM stage, Eastern 
Cooperative Oncology Group performance status 
(ECOG PS), smoking status, PD-L1 expression, 
mutational status of EGFR, KRAS, ALK, ROS 1, 
BRAF and NTRK in adenocarcinoma, time to dur-
valumab start from the end of the RT, treatment 
completion, PFS and OS from the start of ChT-RT 
and the start of durvalumab were collected for the 
analysis. Response rate after ChT-RT was assessed 
using RECIST 1.1 and during immunotherapy 
iRECIST.8 Immune related adverse events were 
assessed by their highest reported grade using 
Common Terminology Criteria for Adverse Events 
(CTCAE) Version 5.0.9
PFS was calculated from the beginning of the 
durvalumab to disease progression or death and 
OS as the time from the start of the durvalumab to 
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Vrankar M et al. / Outcome of lung cancer patients after durvalumab treatment484
death from any cause. Data from the patients who 
had not progressed or had not died were censored 
at the date of last follow-up (February 3, 2021).
The association between the PFS, OS and the 
basic clinicopathological variables of patients were 
tested using the log-rank test. OS and PFS curves 
were estimated using Kaplan-Meier method. The 
Cox proportional hazards model was used to as-
sess the association between PFS, OS and treatment 
characteristics. All tests were two tailed. A p-value 
less than 0.05 was considered statistically signifi-
cant. All p values reported were based on the two-
sided hypothesis. The statistical analyses were cal-
culated using SPSS -21 (IBM Corporation, Armonk, 
NY, USA). 
This study was conducted in accordance 
with the Declaration of Helsinki. The study 
was approved by Institutional Review Board 
Committee and Institutional Ethics Committee 
(ERIDNPVO-0004/2021).
Results 
In total, 118 patients had been identified as candi-
dates for maintenance treatment with durvalumab 
from December 2017 who completed treatment 
until December 2020. Of those, 85 (72.0%) patients 
continued treatment with maintenance durvalum-
ab after ChT-RT and in 33 durvalumab was omit-
ted due to persistent toxicity in 6, treatment refusal 
in 11 and progressive disease in 16 patients. 
Baseline characteristics of 85 patients included 
in the analyses are detailed in Table 1. Most were 
male (70.6%) in stage IIIB (56.5%) with squamous 
cell carcinoma (58.8%), ECOG PS 1 (54.1%). Median 
age was 63 years (range 36–73 years). PD-L1 ex-
pression was positive in 65 (76.5%) patients, in 13 
(15.3%) patients was negative and not available in 
7 patients (8.2%). No EGFR, ALK, ROS 1, BRAF 
and TNRK mutations were detected in 65 (76.5%) 
patients, KRAS mutation was present in 16 (18.8%) 
patients and for 4 patients mutational status was 
not available. 
Treatment with chemoradiotherapy 
Eighty-two (96.5%) patients started treatment with 
induction ChT and 54 (63.5%) patients received 
ChT during RT (Table 2). Thirty-one (36.5%) pa-
tients were treated with sequential ChT only. 
Patients received median 3 cycles (range 1–5) of 
ChT altogether. Seventy-nine patients (92.9%) re-
ceived gemcitabine and cisplatin as induction ChT 
and 52 (61.2%) of those switched to etoposide and 
cisplatin during concurrent treatment with RT. 
Only 3 patients (3.5%) with adenocarcinoma were 
treated with pemetrexed and cisplatin as induc-
tion as well as concurrent regimen. Patients were 
treated with the median RT dose of 60 Gy (range 
54 Gy–66 Gy), and in most of them (82.3%) partial 
response was observed after ChT-RT. 
Treatment with durvalumab
Patients started first cycle of durvalumab after a 
median of 57 days (range 12–99 days) from the end 
of the RT and were treated with the median of 10.8 
months (range 0.5–12 months) (Table 3). Forty-one 
TABLE 1 . Baseline characteristics of patients treated with durvalumab 
N = 85 
Gender
Female 25 (29.4 %)
Male 60 (70.6 %)
Age 
Median (range)
63 (36 – 73)< 63
≥ 63
ECOG PS
0 37 (43.5 %)
1 46 (54.1 %)
2 2 (2.4 %)
Smoking history
Never 2 (2.4 %) 
Ex-smokers 35 (41.6 %)
Smoking at diagnosis 47 (56.0 %)
Histology
Adenocarcinoma 31 (36.5 %)
Squamous Cell 50 (58.8 %)
Other 4 (4.7 %)
AJCC 8th Edition Stage
IIIA 26 (30.6%)
IIIB 48 (56.5 %)
IIIC 11 (12.9 %)
PD-L1 Expression
< 1% 13 (15.3 %)
1%-49% 33 (38.8 %)
> 50% 32 (37.7 %)
Unavailable 7 (8.2 %)
Mutational status
No mutations 65 (76.5 %)
KRAS 16 (18.8 %)
Unavailable 4 (4.7 %)
Abbreviation: N-number, ECOG PS- Eastern Cooperative Oncology Group performance status, 
PD-L1-programmed dead-ligand 1
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Vrankar M et al. / Outcome of lung cancer patients after durvalumab treatment 485
patients (48.2%) completed treatment with planned 
12-month therapy, 25 patients (29.4%) completed 
treatment early due to the toxicity of durvalumab 
and 16 patients (18.8%) due to the disease progres-
sion. One patient died suddenly after two months 
of treatment without progression and no known 
cause of death. One patient stopped treatment after 
TABLE 2. Chemoradiotherapy treatment characteristics 
N = 85 (%)
N of ChT
1 3 (3.5%)
2 13 (15.3%)
3 41 (48.2%)
4 27 (31.8%)
5 1 (1.2%)
ChT
Gem/cis 79 (92.9%)
Etop/cis 52 (61.2%)
Pem/cis 3 (3.5%)
ChT
Induction 82 (96.5%)
Sequential only 31 (36.5%)
Concurrent 54 (63.5%)
Concurrent only 3 (3.5%)
RT dose (Gy) Median (range) 60 (5 –66)
V20 (Gy) Median (range) 27.2 (7.0–35.6)
MLD (Gy) Median (range) 15.7 (4.0–20.2)
PTV (cm3) Median (range) 416.6 (172.3–1282.6)
Evaluation after ChT-RT
CR 10 (11.8%)
PR 70 (82.3%)
SD 5 (5.9 %)
Time between RT-IT 
(days) Median (range) 57 (12–99)
ChT = chemotherapy, CR = complete response; etop/cis = etoposide/cisplatin; gem/cis = 
gimcitabine/cisplatin; IT = immunotherapy; MLD = mean lung dose; N = number of patients; PD = 
progressive disease; PR = partial response; PTV = planning target volume; RT = radiotherapy; pem/
cis = pemetrexed/cisplatin; SD = stable disease; V20 = volume of the lung that receive radiation 
dose of 20 Gy
FIGURE 1. Progression free survival of patients treated with 
durvalumab after sequential or concurrent platinum-based 
chemoradiotherapy.
FIGURE 2. Progression free survival regarding response after 
durvalumab completion.
one month due to newly diagnosed prostate cancer 
and one due to cerebral infarction unrelated to dur-
valumab treatment.
Toxicity of durvalumab treatment
Twenty-five patients (29.4%) discontinued dur-
valumab early due to the toxicity after the me-
dian treatment time of 6.0 months (range 0.5–11 
months). Twelve patients (14.1%) had pneumonitis 
that started significantly earlier after introduction 
of durvalumab than other AE (2.0 months vs. 7.2 
months, p = 0.012). Other AE leading to discontinu-
ation of durvalumab treatment included dermato-
logical toxicity (n = 5), arthralgia (n = 4), colitis (n = 
2) and uncontrolled hypothyroidism (n = 2). Most 
immune related AE leading to discontinuation of 
durvalumab were grade 1–2 (68%), 32% were grade 
3. No grade 4 of 5 AE were observed. 
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Vrankar M et al. / Outcome of lung cancer patients after durvalumab treatment486
In total, 42 (49.6%) patients experienced 47 AE, 
38 patients had 1 AE, three patients had 2 and one 
patient had 3 AE. Pneumonitis was found in 15 
(17.6%), arthralgia in 5 (5.9%), skin toxicity in 13 
(15.3%), colitis in 6 (7.1%) and hypothyroidism in 
8 (9.4%) patients. 
Treatment results
Median PFS from the durvalumab start was 22.0 
months, estimated 12- and 24-month PFS were 
71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–
58.9%) (Figure 1). During durvalumab treatment, 
16 patients progressed after the durvalumab treat-
ment median time of 6.1 months (range 0.5–11.0 
months), 7 with loco-regional and 9 with distant 
metastases. Altogether, 36 (42.4%) patients have 
progressed until the last follow-up date, 21 (24.7%) 
patients with loco-regional failure only and 15 
(17.6%) patients with distant metastatic disease. Of 
those, 5 patients had also local progression. 
Age, gender, ECOG PS, stage, histology, PD-L1 
expression, mutational status, smoking status, RT 
dose, time between end of RT and start of dur-
valumab, time of durvalumab treatment in non-
progressive patients during durvalumab, ChT 
sequential vs. concurrent, did not predict poorer 
PFS in univariate analysis (Table 4). Patients who 
had complete response (CR) on CT evaluation af-
ter durvalumab treatment had significantly longer 
PFS compared to those with partial response (PR) 
or stable disease (SD) (mPFS not reached vs. 22 
months, p = 0.01) and this was affirmed in multi-
variate analysis (Figure 2). 
Regarding the pattern of progression, we found 
more loco-regional only progression in squamous 
cell carcinoma (79.4%) and distant metastases in 
adenocarcinoma (81.8 %), the difference was signif-
icant (p = 0.002) (Table 5). In addition, all patients 
with KRAS mutation that progressed, had distant 
metastases only (p < 0.001). On the contrary, all pa-
tients that discontinued treatment early due to AE 
and progressed later (n = 8), had loco-regional fail-
ure only (p = 0.024).
Median OS from the durvalumab start has not 
been reached after the median follow-up time of 23 
months (range 2–35 months). Twelve- and estimat-
ed 24-month OS were 86.7% (95% CI: 79.5–93.9%), 
and 68.6% (95% CI: 57.2–79.9%), respectively 
(Figure 3). In total, 25 patients (29.4%) have died 
until the last follow-up date.
TABLE 3. Durvalumab treatment characteristics and influence on overall survival
Treatment characteristics N (%) P
Time between RT-IT
Median (days)
57 (12–99) 0.689< 57
≥ 57
Treatment time of IT*
Median (months)
10.8 (0.5–12.0) < 0.001< 10.8
≥ 10.8
Treatment with IT
Completed 41 (48.2%)
0.095
Early stopped due to AE 25 (29.4%)
Progression 16 (18.8%)
Other 3 (3.6%)
Response after IT** 
CR 29 (34.1%)
0.213
PR 11 (12.9%)
SD 15 (17.6%)
PD 10 (11.8%)
Progression***
Loco-regional 21 (24.7%)
0.217
Metastatic 10 (11.7%)
Metastatic and local 5 (5.9%)
Metastatic spread
CNS 5 (5.9%)
0.101
Other 10 (11.7 %)
*difference in overall survival between patients treated with immunotherapy less or more than 
median time;
** including evaluation up to 4 months after completed immunotherapy in patients with 12-month 
therapy as well as in early stopped due to adverse events, later progression is not included. Two 
patients were not evaluable;
*** observed progression until the last evaluation date;
AE = adverse events; CNS = central nerve system; CR =complete response; IT = immunotherapy; 
PD = progressive disease; PR = partial response; RT = radiotherapy; SD = stable disease
FIGURE 3. Overall survival of patients treated with 
durvalumab after sequential or concurrent platinum-based 
chemoradiotherapy.
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Vrankar M et al. / Outcome of lung cancer patients after durvalumab treatment 487
TABLE 4. Univariate and multivariate analysis of predictors for progression free survival 
Variable 
Univariate analysis Multivariate analysis
HR (95% CI) p HR (95 % CI) p
Age 
< 63 years 0.67 (0.35–1.29) 0.231
≥ 63 years
Gender 
Male 0.62 (0.32–1.20) 0.156
Female 
ECOG PS
0 0.66 (0.34–1.28) 0.226
1–2
Stage
IIIA 0.89 (0.54–1.48) 0.663
IIIB
IIIC
Histology 
Adenocarcinoma 0.84 (0.41–1.70) 0.635
Squamous Cell
Smoking status
Never 0.59 (0.33–1.07) 0.084 1.72 (0.26–11.00) 0.567
Ex-smokers
Smoking at diagnosis
Mutational status
No 0.99 (0.87–1.12) 0.881
KRAS
PD-L1
< 1% 1.03 (0.67–1.59) 0.882
1%–49%
> 50%
Time to durvalumab
< 57 days 0.63 (0.32–1.24) 0.186
≥ 57 days
RT dose
< 60 Gy 1.10 (0.43–2.84) 0.838
≥ 60 Gy
No of ChT
Up to 3 2.06 (0.94–4.51) 0.069 0.83 (0.23–2.99) 0.783
4–5
ChT
Sequential 1.51 (0.79–2.85) 0.209
Concurrent 
Response after IT
CR 0.066 (0.008–0.518) 0.010 0.067 (0.008–0.535) 0.011
PR/SD
Durvalumab treatment 
time 
< 10.8 months 3.16 (1.62–6.17) 0.001 1.18 (0.227–6.17 0.841
≥ 10.8 months
CR =complete response; ECOG PS = Eastern Cooperative Oncology Group performance status; ChT =chemotherapy, RT = radiotherapy, IT = 
immunotherapy; PD = progressive disease; PD-L1 = programmed dead-ligand 1; PR =partial response; SD = stable disease 
Age, gender, ECOG PS, stage, histology, PD-L1 
expression, mutational status, smoking status, RT 
dose, ChT sequential vs. concurrent, the time be-
tween end of RT and start of durvalumab did not 
predict poorer OS in univariate analysis. Patients 
with CR after ChT-RT had significant longer sur-
vival with Kaplan-Meier method than patients 
with PR or SD (p = 0.045), however, survival was 
not different according to response after dur-
valumab treatment. In the multivariate Cox pro-
portional hazards model CR after ChT-RT as well 
as after completion of durvalumab was not predic-
tor of better OS. 
Treatment after progression
After progression, six patients had no additional 
treatment, mostly due to progressive deterioration 
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of patient’s performance. Fourteen patients were 
treated with RT only and eleven with ChT, of those 
six received aditional RT and one of them also im-
munotherapy. Two patients had surgery of brain 
metastases and three patients had salvage surgery 
of primary tumour. 
Discussion
The results of PFS and OS in our series of patients 
with stage III NSCLC treated with durvalumab 
after ChT-RT confirmed improved survival com-
pared to our historical data of treatment before 
durvalumab introduction.10-12 After the median 
follow-up time of 23 months, 12- and 24-month 
PFS (71% and 45.8%, respectively) and OS (86.7% 
and 68.6%, respectively) in our series were compa-
rable with those in the PACIFIC trial (PFS 55.3% 
and 44.8% and OS 83.1% and 66.3%).1-4 In addition, 
data from other real-world reports have confirmed 
the advantage of maintenance treatment with dur-
valumab over ChT-RT only.13 -16 In a series of 62 pa-
tients in the report of Offin et al., the 12-month PFS 
and OS were 65% and 85%, respectively.14 In the 
Canadian multicentre analysis with 147 patients 
included, 12-month OS rate of 92.5% was reported 
after a median follow-up of 15.8 months.15 Report 
from the German group encompassed 56 centres 
with altogether 126 patients treated in expanded 
access programme, revealed the 12- and 24-month 
PFS of 56.0% and 46.7%, and 12- and 24-month OS 
of 78.6% and 66.0%, respectively.16
The broad usage of induction ChT before RT, 
and ChT selection of gemcitabine in our group of 
stage III NSCLC patients offered comparable sur-
vival rates and safety as reported with other sched-
ules in recent publications.14-16 Some patients with 
stage III NSCLC are not candidates for concurrent 
ChT-RT due to the age and comorbidity.5,6 Most pa-
tients (96.5 %) in our series started treatment with 
ChT, majority of them with platinum-based ChT 
including gemcitabine and 63.5% of all continued 
platinum-based ChT during RT. In the PACIFIC 
study, only 25.8% of patients were treated with in-
duction ChT and 99.8% of patients with concurrent 
platinum-based ChT with etoposide, vinblastine, 
vinorelbine, taxans or pemetrexed.1,17 Only few 
patients in PACIFIC trial were treated with gem-
citabine, and additionally, gemcitabine was not 
used in none of the recently published real-world 
durvalumab treatment reports. In the real-world 
reports of durvalumab treatment, platinum-based 
ChT with etoposide was used in 11.0% to 21.8% of 
all patients concurrent with RT, and induction ChT 
was used in up to 32.5% of patients.14-16
Treatment with induction gemcitabine in our 
historical analysis had not revealed excessive AE 10-
12. Induction, sequential and concomitant regimes 
were well tolerated also in the present series (data 
not shown). In present analysis, there were no dif-
ferences in PFS and OS between the patients treat-
ed with sequential ChT only or concurrent ChT. 
Additionally, the effectiveness of platinum-based 
ChT with induction gemcitabine was not inferior 
to other ChT schedules when comparing PFS and 
OS. Comparing the best response to ChT-RT, we 
observed a higher rate of CR and PR (11.8% and 
82.3%) than the PACIFIC trial (1.9% and 48.7%).1-4 
The median time to first cycle of durvalumab from 
the end of RT in our series was 57 days (range 
12–99 days) which is considerably longer than in 
PACIFIC trial (range 1–42 days), and longer as re-
ported by Offin with a median time of 1.5 months 
(range 0.3–7.7 months), and Desilets with 33 days 
(range 1–94 days).14,15 Early completed durvalum-
ab treatment due to progression in our analysis 
was observed in 18.8% of patients as compared 
to 30.2% in PACIFIC trial and 34.1% reported by 
Faehling.1,16 At the evaluation up to 4 months after 
the completion of durvalumab treatment (planned 
12-month therapy or early completed due to AE), 
we observed CR, PR and SD in 34.1%, 12.9% and 
17.6% of patients. Notably, the only predictor for 
improved PFS in our series was CR compared to 
TABLE 5. Pattern of progression 
Progression (N of patients) Loco-regional only Metastatic p
Gender 
Male 12 10
0.563
Female 9 5
Stage 
IIIA 7 3
0.663IIIB 11 9
IIIC 3 3
Histology 
Adenocarcinoma 2 9
0.002Squamous cell 19 5
Other 0 1
Mutation 
KRAS 0 7
< 0.001
No mutation 21 8
PD-L1
< 1% 3 4
0.4351%–49 % 8 6
50 % 10 4
N = number; PD-L1 = programmed dead-ligand 1
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Vrankar M et al. / Outcome of lung cancer patients after durvalumab treatment 489
PR/SD after durvalumab treatment that was con-
firmed in multivariate analysis (p = 0.032). 
Baseline characteristics of patients in our se-
ries differed from patients in PACIFIC trial. In our 
analysis, more patients in stage IIIB and IIIC (69.4% 
vs. 47.0%) were included and more patients had 
squamous cell carcinoma (58.1% vs. 47.1%). Both 
characteristics are known predictors for worse 
prognosis.18,19 Two real-world analysis similarly 
reported 72% and 68.3% of patients included in 
stage IIIB and IIIC NSCLC, but lower proportion 
of squamous cell carcinoma, ranged from 31% to 
42.6%.14,16 Squamous cell lung carcinoma is associ-
ated with inferior OS in all stage groups including 
unresectable stage III NSCLC.20  Some reports indi-
cated that patients with squamous-cell carcinoma 
typically presented with bulky locally advanced 
disease and in those patients, it might be an ad-
vantage to start treatment with induction ChT as 
it was the case in our series.16 In our analysis, no 
difference in PFS and OS regarding histology was 
revealed, but significantly more loco-regional pro-
gression was observed compared to metastatic pro-
gression in squamous cell carcinoma (p = 0.002) as 
in adenocarcinoma. Altogether, 24.7% of patients 
had loco-regional progression only and 17.6% had 
progression with metastatic disease. On the con-
trary, Offin et al. reported the 12-month incidence 
of loco-regional and distant failures of 18% and 
30%.14 High proportion of loco-regional progres-
sion in our series might be due to high proportion 
of squamous cell carcinoma. 
The salvage treatment for most patients with 
loco-regional progression was reirradiation with 
or without reinduction ChT. Three patients in 
our series had salvage surgery due to progres-
sive primary tumour with observed regression 
of the lymph nodes. In all, the histology revealed 
down-staging of the lymph nodes and persistent 
malignant cells in the primary tumour. The high 
proportion of loco-regional failures only opens the 
important emerging issue how to deal with the 
patients after completion of ChT-RT and mainte-
nance durvalumab with PR or SD. Regarding our 
results, surgery might be an appropriate additional 
treatment option in selected patients with PR, es-
pecially in patients with squamous cell carcinoma. 
Further clinical trials are investigating incorpora-
tion of immunotherapy at different time point in 
treatment with ChT-RT in stage III NSCLC pa-
tients. Additionally, the research in modulating the 
immune response by interfering with specific alter-
native immune receptors, pathways and mediators 
is ongoing and might offer additional knowledge 
that would affect the treatment of stage III NSCLC 
patients.21 However, as demonstrated in advanced 
NSCLC, one treatment might not be suitable for all 
and in the future, it could be revealed that person-
alized multimodality approach for selected stage 
III NSCLC patients might enable better survival 
results. 
Our results presented here were collected as a 
single institution experience. Due to small number 
of patients, this series might be underpowered to 
detect significant impact on survival for different 
treatment regimens and probable prognostic vari-
able. Also, some information in statistical analysis 
might be lost, due to dichotomisation of continu-
ous data. Due to retrospective nature of the analy-
sis, some data were not available for all patients. 
However, despite more advanced stage III NSCLC 
and squamous cell histology, our results are con-
sistent with the PACIFIC trial. Additionally, fur-
ther studies are warranted assessing management 
of patients with loco-regional SD or PR after dur-
valumab treatment. 
Conclusions
The survival data in present analysis confirmed the 
advantage of maintenance durvalumab in the treat-
ment of unresectable stage III NSCLC patients over 
ChT-RT only and our results are in line with the 
PACIFIC trial as well as with recently published 
real-world reports. Additionally, with mostly gem-
citabine as induction platinum-based ChT, the sur-
vival outcomes confirmed our treatment regimen 
as efficient and well tolerated. 
Acknowledgments 
We thank all the patients who participated in this 
study.
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