Highlights
- •Treatment sequencing is a viable option for NSCLC with a PD-L1 expression ≥ 50%.
- •Post-progression pathways of a cohort of NSCLC receiving pembrolizumab were reported.
- •Post-progression outcomes are major determinants for worse clinical outcomes.
- •Our results should be considered when counselling patients for first-line choices.
Abstract
Background
Treatment sequencing with first-line immunotherapy, followed by second-line chemotherapy,
is still a viable option for NSCLC patients with PD-L1 expression ≥50%.
Methods
We evaluated post-progression treatment pathways in a large real-world cohort of metastatic
NSCLC patients with PD-L1 expression ≥ 50% treated with first-line pembrolizumab monotherapy.
Results
Overall, 974 patients were included. With a median follow-up of 22.7 months (95%CI:
21.6–38.2), the median overall survival (OS) of the entire population was 15.8 months
(95%CI: 13.5–17.5; 548 events). At the data cutoff, among the 678 patients who experienced
disease progression, 379 (55.9%) had not received any further treatment, and 359 patients
(52.9%) had died. Patients who did not receive post-progression therapies were older
(p = 0.0011), with a worse ECOG-PS (p < 0.0001) and were on corticosteroids prior
to pembrolizumab (p = 0.0024). At disease progression, 198 patients (29.2%) received
a switched approach and 101 (14.9%) received pembrolizumab ByPD either alone (64 [9.4%])
or in combination with local ablative treatments (37 [5.5%]) (LATs). After a random-case
control matching according to ECOG-PS, CNS metastases, bone metastases, and (previous)
best response to pembrolizumab, patients receiving pembrolizumab ByPD plus LATs were
confirmed to have a significantly longer post-progression OS compared to patients
receiving pembrolizumab ByPD alone 13.9 months versus 7.8 months (p = 0.0179) 241
patients (35.5%) among the 678 who had experienced PD, received a second-line systemic
treatment (regardless of previous treatment beyond PD). As compared to first-line
treatment commencement, patients’ features at the moment of second-line initiation
showed a significantly higher proportion of patients aged under 70 years (p = 0.0244),
with a poorer ECOG-PS (p < 0.0001) and having CNS (p = 0.0001), bone (p = 0.0266)
and liver metastases (p = 0.0148).
Conclusions
In the real-world scenario NSCLC patients with PD-L1 expression ≥50% treated with
first-line single-agent pembrolizumab achieve worse outcomes as compared to the Keynote-024
trial. Poor post-progression outcomes are major determinants of the global results that
should be considered when counselling patients for first-line treatment choices.
Keywords
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Article info
Publication history
Published online: March 12, 2021
Accepted:
February 11,
2021
Received in revised form:
February 6,
2021
Received:
November 27,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Re: Post-progression outcomes of NSCLC patients with PD-L1 expression ≥50% receiving first-line single-agent pembrolizumab in a large multicentre real-world studyEuropean Journal of CancerVol. 155
- PreviewWe read a very interesting article by Cortellini et al. in which they compared treatment regimens used in the progression that develops after pembrolizumab monotherapy in patients with PD-L1 >50% [1]. A standard recommendation is to use immunotherapies as first-line treatment in a PD-L1-positive patient. In addition, current data in the literature regarding the continuation of immunotherapy agents during progression is deficient.
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