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Two studies to
be reported at ELCC 2019 (1,2) provide new insights on the efficacy
and safety of immunotherapy in elderly patients with advanced
non-small-cell lung cancer (NSCLC), where information has
previously been lacking despite being the age group most commonly
affected.
Immunotherapy
with drugs that target immune pathways to enhance the body’s
ability to recognise and destroy tumour cells is emerging as an
effective treatment option for patients with advanced NSCLC (3).
Although around half of all people newly diagnosed with NSCLC are
elderly (4) there is currently limited evidence on the efficacy and
safety of immunotherapy in this age group because they have been
under-represented in clinical trials. There have also been concerns
that age-related decline in the immune system might affect the
efficacy of immunotherapy in older patients.
Real-life study suggests shorter overall survival
with immunotherapy in elderly
A retrospective
study of patients with advanced NSCLC treated with immunotherapy in
real-life clinical practice (1) suggested that elderly patients (>70
years) may have shorter overall survival than younger patients but
demonstrated that toxicity was similar.
Researchers
retrospectively reviewed all patients with advanced NSCLC treated
with immunotherapy agents at Hospital Universitario Ramon y Cajal
in Madrid, Spain, between 2014 and 2018. Just over one in four (27
patients; 27.5%) of the 98 patients treated with immunotherapy
agents over this four-year period were aged 70 years or older.
PD-L1 status was known in 50% of patients.
Overall survival
in these elderly patients was significantly shorter than in
patients younger than 70 years of age (median 5.5 months vs 13
months, hazard ratio [HR] 3.86, 95% confidence interval [CI]
2.073-7.214, p<0 .0001="" 1.181-3.744="" 2.1="" 3.6="" 95="" also="" ci="" elderly="" hr="" in="" months="" p="0.012).<o:p" patients="" progression-free="" shorter="" significantly="" survival="" than="" vs="" was="" younger="">
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Considering
toxicity, there were no statistically significant differences in
immune-related adverse events between elderly and younger patients
(p=0.535).
The study shows
that immunotherapy was administered mainly as second-line treatment
(61% of patients) or third-line or later (24.5%) across the entire
group of 98 patients of all ages. Just over half (52%) were treated
with nivolumab.
“Our results suggest that
elderly patients could have worse survival outcomes with
immunotherapy than younger patients, without differences in terms
of toxicity,” said study authors Elena Corral de la Fuente and
Arantzazu Barquin Garcia, from the Hospital Universitario Ramon y
Cajal, Madrid, Spain. They acknowledged that the study was limited
by being an observational retrospective analysis with a small
sample size. They suggested, “Prospective randomised clinical
trials and more real-world data are needed to answer remaining
questions on the use of immunotherapy in elderly patients.”
Pooled analysis demonstrates improved overall
survival with immunotherapy
A second study
pooling data from three randomised trials (2) shows significantly
improved overall survival in elderly patients with advanced NSCLC
treated with the immunotherapy agent pembrolizumab compared to
those given chemotherapy.
The study
compared the efficacy and safety results for 264 elderly patients
aged > 75 years in the three trials with results for 2292
participants younger than 75 years. All of the patients had PD-L1
tumour proportion scores (PD-L1 TPS) of 1% or higher and half of
the elderly group in this analysis had scores of at least 50% (5).
Results show
significantly improved overall survival in elderly patients with
PD-L1 tumours scores >1% treated with pembrolizumab
compared to those treated with chemotherapy (hazard ratio [HR]
0.76, 95% confidence interval [CI] 0.56-1.02). The improvement in
overall survival with pembrolizumab compared to chemotherapy was
even greater in patients with PD-L1 tumour scores >50%
(HR 0.41, 95% CI 0.23-0.73).
One-year overall
survival rates with pembrolizumab in elderly patients were
comparable to those in younger patients (53.7% vs 54.9% in PD-L1
TPS >1% and 61.7% vs 61.7% in PD-L1 TPS >50%).
Fewer elderly
patients treated with pembrolizumab had treatment-related adverse
events compared to those treated with chemotherapy (68% vs 94%).
Grade 3-5 treatment-related adverse events in elderly patients were
also less common with pembrolizumab compared to chemotherapy (24%
vs 61%). Common treatment-related adverse events with pembrolizumab
in elderly patients were fatigue (17.4%), decreased appetite
(12.8%) and pruritus (12.8%).
Immune-mediated
adverse events and infusion reactions were more frequent with
pembrolizumab vs chemotherapy in the elderly group of patients (25%
vs 7%) but showed no difference compared to younger patients
treated with pembrolizumab (25%).
“In elderly patients with
advanced NSCLC with PD-L1–positive tumours, pembrolizumab
monotherapy improved overall survival over chemotherapy, together
with a more favourable safety profile,” said lead author Kaname
Nosaki, from the National Hospital Organization Kyushu Cancer
Center, Fukuoka, Japan. He added, “Our data support the use of
pembrolizumab monotherapy in elderly patients (≥75 years) with
advanced PD-L1‒expressing NSCLC.”
Considering potential limitations, Nosaki noted that the elderly
patients included in the pooled analysis met the inclusion criteria
for each of the individual studies, which would have selected for a
relatively fit elderly patient population.
Commenting on the
studies, Marina Garassino, Chief of Thoracic Oncology at the
Istituto Nazionale dei Tumori, Milan, Italy, said, “The pooled
analysis of clinical trials showed no difference in the efficacy
and safety of immunotherapy in the elderly compared to younger patients.
But the real-world study is an alarm bell potentially suggesting
lower efficacy with immunotherapy in elderly patients despite no
difference in adverse events.” In terms of limitations, she noted
that PL-1 expression was known in only 50% of patients included in
the real-world study and that data were collected retrospectively.
“Data collected in real-world studies are not controlled as
precisely as in randomised trials,” she noted, but added that
elderly patients are generally under-represented in clinical
trials.
Looking to the
future, Garassino concluded, “We need larger, prospective trials or
larger real-world studies to gain a more detailed view on the
efficacy and safety of immunotherapy in elderly patients with
NSCLC.”
-END-
Notes to Editors
Please make sure to use the official name of the
meeting in your reports: European Lung Cancer Congress (ELCC)
2019
Official Congress hashtag: #ELCC19
Disclaimer
This press release contains information provided by
the authors of the highlighted abstracts and reflects the content
of these abstracts. It does not necessarily reflect the views or
opinions of ESMO or IASLC who cannot be held responsible for the
accuracy of the data. Commentators quoted in the press release are
required to comply with the ESMO Declaration of Interests policy
and the ESMO Code of Conduct.
References
1 Abstract 169P_PR ‘Benefit of immunotherapy (IT) in
advanced non-small cell lung cancer (NSCLC) in elderly patients
(EP)’ will be presented by Elena Corral de la Fuente during the Poster
Display Session on Thursday, 11 April 2019, 12:30 (CEST) in Hall 1.
Annals of Oncology, Volume 30, 20019 Supplement 2.
doi:10.1093/annonc/mdz072
2 Abstract 103O_PR ‘Safety and efficacy of
pembrolizumab (Pembro) monotherapy in elderly patients (Pts) with
PD-L1-positive advanced NSCLC: Pooled analysis from KEYNOTE-010,
-024 and -042’ will be presented by Kaname Nosaki during the
ESMO-IASLC Best Abstracts Session on Thursday, 11 April 2019, 14:45
(CEST) in Room B. Annals of Oncology, Volume 30, 20019 Supplement
2. doi:10.1093/annonc/mdz07
The pembrolizumab study pooled results from three
randomised, controlled trials:
- KEYNOTE-010 included patients with advanced
NSCLC and PD-L1 tumour proportion score > 1%.
Patients were randomised to pembrolizumab (2 or 10mg/kg once
every three weeks) or docetaxel, as second- or later-line
therapy.
- KEYNOTE-042 also included patients with
advanced NSCLC and PD-L1 tumour proportion score >
1%. Patients were randomised to first-line pembrolizumab
(200mg/kg once every three weeks) or platinum-based
chemotherapy.
- KEYNOTE-024 included patients with advanced
NSCLC and PD-L1 tumour proportion score > 50%.
Patients were randomised to first-line pembrolizumab (200mg/kg
once every three weeks) or platinum-based chemotherapy.
3 Planchard D,
Popat S, Kerr K et al. Metastatic non-small cell lung cancer: ESMO
Clinical Practice Guidelines for diagnosis, treatment and
follow-up. Annals of Oncology 2018; 29 (supplement 4); iv192-iv237.
4 Pallis AG, Gridelli C, Wedding U et al. Management of elderly
patients with NSCLC; updated expert’s opinion paper: EORTC Elderly
Task Force, Lung Cancer Group and International Society for
Geriatric Oncology. Annals of Oncology 2014; 25: 1270-1283.
5 PD-L1 TPS measures the proportion of tumour cells expressing
PD-L1 (programmed-death ligand 1), which is the main ligand for the
key immune checkpoint inhibitory receptor PD-1. A PD-L1 score of
>1% means that at least 1% of tumour cells express PD-L1, while
a PD-L1 score of >50% indicates high PD-L1 expression, with at
least 50% of tumour cells expressing PD-L1.
About the European Society for Medical Oncology
(ESMO)
ESMO is the leading professional organisation for
medical oncology. With more than 20,000 members representing
oncology professionals from over 150 countries worldwide, ESMO is
the society of reference for oncology education and information.
ESMO is committed to offer the best care to people with cancer,
through fostering integrated cancer care, supporting oncologists in
their professional development, and advocating for sustainable
cancer care worldwide.
About the International Association for the Study
of Lung Cancer (IASLC)
The International Association for the Study of Lung
Cancer (IASLC) is the only global organisation dedicated solely to
the study of lung cancer and other thoracic malignancies. Founded
in 1974, the association's membership includes more than 6,500 lung
cancer specialists across all disciplines in over 100 countries,
forming a global network working together to conquer lung and
thoracic cancers worldwide. The association also publishes the
Journal of Thoracic Oncology, the primary educational and informational
publication for topics relevant to the prevention, detection,
diagnosis and treatment of all thoracic malignancies. Visit
www.iaslc.org for more information and follow us on Twitter @IASLC.
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103O_PR - Safety and efficacy of pembrolizumab
(Pembro) monotherapy in elderly patients (Pts) with
PD-L1–positive advanced NSCLC: Pooled analysis from KEYNOTE-010,
-024, and -042
K. Nosaki1,
Y. Hosomi2, H. Saka3, P. Baas4,
G. de Castro Jr5, M. Reck6, Y-L. Wu7,
J.R. Brahmer8, E. Felip9, T. Sawada10,
K. Noguchi10, S.R. Han10, B. Piperdi11,
D.A. Kush11, G. Lopes12
1National
Hospital Organization Kyushu Cancer Center, Fukuoka, Japan, 2Tokyo
Metropolitan Cancer and Infectious Diseases Center Komagome
Hospital, Tokyo, Japan, 3National Hospital
Organization Nagoya Medical Center, Nagoya, Japan, 4The
Netherlands Cancer Institute and The Academic Medical Hospital
Amsterdam, Amsterdam, Netherlands, 5Instituto do
Câncer do Estado de São Paulo, Sao Paulo, Brazil, 6Lung
Clinic Grosshansdorf, Airway Research Center North (ARCN), German
Center for Lung Research (DZL), Grosshansdorf, Germany, 7Guangdong
Lung Cancer Institute, Guangdong General Hospital, Guangdong
Academy of Medical Sciences, Guangdong, China, 8Sidney
Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,
MD, USA, 9Vall d'Hebron University Hospital,
Barcelona, Spain, 10MSD K.K., Tokyo, Japan, 11Merck
& Co., Inc., Kenilworth, NJ, USA, 12Sylvester
Comprehensive Cancer Center at the University of Miami, Miami,
FL, USA
Background: Approximately 70% of newly-diagnosed NSCLC cases
occur in the elderly, and more than half are locally
advanced/metastatic. We present a pooled analysis of efficacy and
safety in elderly pts (aged ≥75 y) enrolled in 3 randomized
controlled trials of pembro monotherapy vs standard chemotherapy
(chemo) for PD-L1–positive advanced NSCLC.
Methods: Pts were
aged ≥18 y with advanced NSCLC with PD-L1 tumor proportion score
(TPS) ≥1% (KEYNOTE-010, -042) or TPS ≥50% (KEYNOTE-024). In
KEYNOTE-010, pts were randomized to pembro 2 or 10 mg/kg Q3W or
docetaxel, as second- or later-line therapy. In KEYNOTE-024 and
-042, pts were randomized to first-line pembro 200 mg Q3W or
platinum-based chemo. OS was estimated by the Kaplan-Meier
method.
Results: The 3
trials included 264 pts aged ≥75 (range, 75–90) y with TPS ≥1%;
132 pts had TPS ≥50%. Independent of line of treatment, HRs (95%
CI) for OS favored pembro vs chemo: 0.76 (0.56–1.02) in pts with
TPS ≥1% and 0.40 (0.25–0.64) in pts with TPS ≥50%. Pembro also
improved OS vs chemo in the pooled analysis of pts with TPS ≥50%
who received first-line therapy (KEYNOTE-024 and -042): HR, 0.41
(95% CI, 0.23–0.73). Overall, fewer treatment-related AEs across
various categories were observed with pembro vs chemo, in
particular, grade 3–5 treatment-related AEs in pts aged ≥75 y
(Table). Immune-mediated AEs and infusion reactions were more
frequent with pembro vs chemo, with similar frequency in pts
receiving pembro aged ≥75 y and <75 -024="" -042.="" able="" age="" and="" by="" from="" group="" in="" keynote-010="" o:p="" of="" pd-l1="" pooled="" pts="" results="" safety="" summary="" table.="" tps="" with="" y="">
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Pembro
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Chemo
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AEs, n
(%)
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≥75 y
n = 149
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<75 span="" y="">
n = 1323
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≥75 y
n = 105
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<75 span="" y="">
n = 969
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Any
treatment-related AE
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102
(68)
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862
(65)
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99
(94)
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840
(87)
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Grade 3–5
treatment-related AE
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36
(24)
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224
(17)
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64
(61)
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379
(39)
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Serious
treatment-related AE
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24
(16)
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170
(13)
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28
(27)
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136
(14)
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Treatment-related
AEs leading to discontinuation
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16
(11)
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90
(7)
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16
(15)
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93
(10)
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Treatment-related
AEs leading to death
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2
(1)
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17
(1)
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2
(2)
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20
(2)
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Immune-mediated
AEs and infusion reactions
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37
(25)
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331
(25)
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7
(7)
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57
(6)
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Conclusions: In this pooled analysis of pts aged ≥75 y with
PD-L1–positive advanced NSCLC, pembro monotherapy improved OS vs
chemo, both in pts with PD-L1 TPS ≥1% and PD-L1 TPS ≥50%. The
safety profile of pembro was similar in pts aged ≥75 y and <75 3="" aes="" chemo.="" grade="" lower="" o:p="" of="" rates="" treatment-related="" vs="" with="" y="">
Clinical trial identification: NCT01905657 (KEYNOTE-010); NCT02142738
(KEYNOTE-024); NCT02220894 (KEYNOTE-042)
Editorial acknowledgement: Medical writing and editorial assistance was
provided by Michael S. McNamara, MS, of C4 MedSolutions, LLC
(Yardley, PA), a CHC Group company. This assistance was funded by
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,
Inc., Kenilworth, NJ, USA.
Legal entity responsible for the
study: Merck Sharp & Dohme Corp., a subsidiary
of Merck & Co., Inc., Kenilworth, NJ, USA
Funding: This
research was supported by Merck Sharp & Dohme Corp., a
subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
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Disclosure:
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K.
Nosaki: Honoraria: AstraZeneca, Chugai Pharmaceutical, Eli
Lilly, MSD; Institutional research funding: MSD.
Y. Hosomi: Personal fees: MSD, AstraZeneca, Eli Lilly Japan,
Taiho Pharmaceutical, Chugai Pharmaceutical, Ono
Pharmaceutical, Bristol-Myers Squibb.
H. Saka: Grants/research support: AstraZeneca, MSD, Ono
Pharmaceutical; Honoraria: AstraZeneca, MSD, Ono
Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim,
Kyorin Pharmaceutical.
P. Baas: Consulting role: Genentech/Roche, Merck, Bristol-Myers
Squibb, Pfizer; Research support: Bristol-Myers Squibb, Roche,
Merck.
G. de Castro Jr: Consulting/advisory role: AstraZeneca, MSD,
BMS, Roche, Novartis, Boehringer Ingelheim; Speakers’ bureau:
MSD, BMS, Novartis, AstraZeneca; Travel/accommodation expenses:
MSD, BMS, Roche, Bayer, Novartis, Boehringer Ingelheim,
AstraZeneca.
M. Reck: Personal fees: Amgen, Hoffmann-La Roche, Lilly,
AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb,
Celgene, MSD, Merck, Novartis, Pfizer, AbbVie.
Y-L. Wu: Honoraria: AstraZeneca, Eli Lilly, Roche, Pierre
Fabre, Pfizer, Sanofi; Consulting/advisory role: AstraZeneca,
Roche, Merck, Boehringer Ingelheim; Research funding to
institution: Boehringer Ingelheim, Roche.
J.R. Brahmer: Grant, personal fees, Advisory boards,
consulting: Merck; Uncompensated advisor and consultant:
Bristol-Myers Squibb; Grants: Bristol-Myers Squibb,
MedImmune/AstraZeneca; Personal fees: Amgen, Celgene, Lilly.
E. Felip: Consulting, advisory role, speaker’s bureau: AbbVie,
AstraZeneca, Blueprint Medicines, Boehringer Ingelheim,
Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Health,
Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer,
Roche, Takeda; Research funding: Fundación Merck Salud; Grant
for Oncology Innovation EMD Serono.
T. Sawada, K. Noguchi, S.R. Han: Employee: MSD K.K., Tokyo,
Japan.
B. Piperdi, D.A. Kush: Employee of Merck Sharp & Dohme
Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ,
USA.
G. Lopes: Research funding to institution: Merck & Co.,
Inc., EMD Serono, AstraZeneca.
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169P_PR - Benefit of
immunotherapy (IT) in advanced non-small cell lung cancer (NSCLC)
in elderly patients (EP)
E. Corral de la
Fuente1, A. Barquín García2, C. Saavedra
Serrano3, M.E. Olmedo García3, R. Martin
Huertas2, J.J. Serrano Domingo2, V.
Albarrán Artahona2, A. Gómez Rueda3
1Oncology,
Hospital Universitario Ramon y Cajal, Madrid, Spain, 2Hospital
Universitario Ramon y Cajal, Madrid, Spain, 3Medical
Oncology, Hospital Universitario Ramon y Cajal, Madrid, Spain
Background: Despite EP (aged ≥70 years) represent the majority
of patients with advanced NSCLC, the efficacy and toxicity rates
of IT remain poorly described, as they are under-represented in
clinical trials. Furthermore, the age-related decline in the
immune system might affect efficacy of IT.
Methods: We
retrospectively reviewed advanced NSCLC patients treated with IT
(antiPD-1, anti-PD-L1) monotherapy as first, second and
subsequent-line settings, between 2014 and 2018 in our hospital.
Patient and tumor features, irAEs, concomitant and subsequent
treatments were collected. Stata 14.1 was used for the analysis.
Results: 98
patients were included. Mean age was 62 years (41-85). 73.5% were
men. 73.5% had >30 smoked pack-years (py), 64.3% were
adenocarcinoma (ADC), of which 41% were KRAS mutated; and 25.5%
were squamous (SCC). PDL1 was known in a 50% of patients (11%
<1 1-49="" 13="" 25="">50%). IT was administered mainly as a
second line (61%) and third or later (24.5%). Most employed drug
was nivolumab (52%) (Table1). Response Rate (RR) was 32.7%
(partial response 28%, complete response 5%). Disease control
rate (DCR) was 55%. Overall Survival (OS) was significantly lower
in EP compared to patients aged <70 -="" 0.244="" 0.45="" 0.840="" 1.181="" 13="" 2.073-="" 2.1="" 3.6m="" 3.744="" 3.86="" 30.6="" 5.5m="" 7.214="" and="" associated="" better="" between="" development="" differences="" ep="" for="" hr="" ic="" impact="" in="" iraes="" m="" months="" no="" o:p="" of="" on="" os.="" p="0.012)" patients="" pfs="" progression-free="" regarding="" reported.="" significant="" significantly="" statistically="" survival="" terms="" than="" the="" there="" toxicity="" vs="" was="" were="" with="" without="" worse="" years="" younger="">
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Table
1
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Feature
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N
(%)
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Sex
Male Female
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72
(73.5) 26 (26.5)
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Age
<70 o:p="">
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71
(72.5) 27 (27.5)
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Tobacco
≥30 py <30 never="" o:p="" py="" unknown="">
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72
(73.5) 17 (17.4) 2 (2) 7 (7)
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Histology
SCC ADC Unspecified
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25
(25.5) 63 (64.29) 10 (10)
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PDL1
<1 1-49="" o:p="" unknown="">
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11
(11.2) 13 (13.3) 25 (25.5) 49 (50)
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Conclusions: Our
results suggest that EP could have worse survival outcomes than
younger patients, without differences in terms of toxicity, but
prospective trials are needed to confirm this hypothesis.
Legal entity responsible for the study: Elena Corral de la Fuente
Funding: Has not
received any funding
Disclosure: All
authors have declared no conflicts of interest.
