2023年
No.7
PubMed
(tuberculosis[Title/Abstract]) OR (lung cancer[Title/Abstract])
Filters applied: from 2023/7/1 - 2023/7/31.
1. Lancet. 2023 Jul 18:S0140-6736(23)01384-3. doi: 10.1016/S0140-6736(23)01384-3. Online ahead of print.
Stereotactic ablative radiotherapy with or without immunotherapy for early-stage
or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer:
an open-label, randomised, phase 2 trial.
Chang JY(1), Lin SH(2), Dong W(3), Liao Z(2), Gandhi SJ(2), Gay CM(4), Zhang
J(4), Chun SG(2), Elamin YY(4), Fossella FV(4), Blumenschein G(4), Cascone T(4),
Le X(4), Pozadzides JV(4), Tsao A(4), Verma V(2), Welsh JW(2), Chen AB(2), Altan
M(4), Mehran RJ(5), Vaporciyan AA(5), Swisher SG(5), Balter PA(6), Fujimoto
J(7), Wistuba II(7), Feng L(3), Lee JJ(3), Heymach JV(4).
Author information:
(1)Department of Radiation Oncology, The University of Texas MD Anderson Cancer
Center, Houston, TX, USA. Electronic address: jychang@mdanderson.org.
(2)Department of Radiation Oncology, The University of Texas MD Anderson Cancer
Center, Houston, TX, USA.
(3)Department of Biostatistics, The University of Texas MD Anderson Cancer
Center, Houston, TX, USA.
…
BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment
for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but
regional or distant relapses, or both, are common. Immunotherapy reduces
recurrence and improves survival in people with stage III NSCLC after
chemoradiotherapy, but its utility in stage I and II cases is unclear. We
therefore conducted a randomised phase 2 trial of SABR alone compared with SABR
with immunotherapy (I-SABR) for people with early-stage NSCLC.
METHODS: We did an open-label, randomised, phase 2 trial comparing SABR to
I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years
or older with histologically proven treatment-naive stage IA-IB (tumour size ≤4
cm, N0M0), stage IIA (tumour size ≤5 cm, N0M0), or stage IIB (tumour size >5 cm
and ≤7 cm, N0M0) as per the American Joint Committee on Cancer version 8 staging
system or isolated parenchymal recurrences (tumour size ≤7 cm) NSCLC (TanyNanyM0
before definitive surgery or chemoradiotherapy) were included in this trial.
Participants were randomly assigned (1:1; using the Pocock & Simon method) to
receive SABR with or without four cycles of nivolumab (480 mg, once every 4
weeks, with the first dose on the same day as, or within 36 h after, the first
SABR fraction). This trial was unmasked. The primary endpoint was 4-year
event-free survival (local, regional, or distant recurrence; second primary lung
cancer; or death). Analyses were both intention to treat (ITT) and per protocol.
This trial is registered with ClinicalTrials.gov (NCT03110978) and is closed to
enrolment.
FINDINGS: From June 30, 2017, to March 22, 2022, 156 participants were randomly
assigned, and 141 participants received assigned therapy. At a median 33 months'
follow-up, I-SABR significantly improved 4-year event-free survival from 53%
(95% CI 42-67%) with SABR to 77% (66-91%; per-protocol population, hazard ratio
[HR] 0·38; 95% CI 0·19-0·75; p=0·0056; ITT population, HR 0·42; 95% CI
0·22-0·80; p=0·0080). There were no grade 3 or higher adverse events associated
with SABR. In the I-SABR group, ten participants (15%) had grade 3 immunologial
adverse events related to nivolumab; none had grade 3 pneumonitis or grade 4 or
higher toxicity.
INTERPRETATION: Compared with SABR alone, I-SABR significantly improved
event-free survival at 4 years in people with early-stage treatment-naive or
lung parenchymal recurrent node-negative NSCLC, with tolerable toxicity. I-SABR
could be a treatment option in these participants, but further confirmation from
a number of currently accruing phase 3 trials is required.
FUNDING: Bristol-Myers Squibb and MD Anderson Cancer Center Alliance, National
Cancer Institute at the National Institutes of Health through Cancer Center Core
Support Grant and Clinical and Translational Science Award to The University of
Texas MD Anderson Cancer Center.
Copyright © 2023 Elsevier Ltd. All rights reserved.
DOI: 10.1016/S0140-6736(23)01384-3
PMID: 37478883
2. Nature. 2023 Jul;619(7971):851-859. doi: 10.1038/s41586-023-06253-8. Epub 2023
Jul 19.
p53 governs an AT1 differentiation programme in lung cancer suppression.
Kaiser AM(1), Gatto A(#)(2), Hanson KJ(#)(1)(3), Zhao RL(1), Raj N(1), Ozawa
MG(2), Seoane JA(4), Bieging-Rolett KT(1), Wang M(1), Li I(5), Trope WL(6), Liou
DZ(6), Shrager JB(6), Plevritis SK(5), Newman AM(5), Van Rechem C(2), Attardi
LD(7)(8).
Author information:
(1)Division of Radiation and Cancer Biology, Department of Radiation Oncology,
Stanford University School of Medicine, Stanford, CA, USA.
(2)Department of Pathology, Stanford University School of Medicine, Stanford,
CA, USA.
(3)Department of Genetics, Stanford University School of Medicine, Stanford, CA,
USA.
…
Lung cancer is the leading cause of cancer deaths worldwide1. Mutations in the
tumour suppressor gene TP53 occur in 50% of lung adenocarcinomas (LUADs) and are
linked to poor prognosis1-4, but how p53 suppresses LUAD development remains
enigmatic. We show here that p53 suppresses LUAD by governing cell state,
specifically by promoting alveolar type 1 (AT1) differentiation. Using mice that
express oncogenic Kras and null, wild-type or hypermorphic Trp53 alleles in
alveolar type 2 (AT2) cells, we observed graded effects of p53 on LUAD
initiation and progression. RNA sequencing and ATAC sequencing of LUAD cells
uncovered a p53-induced AT1 differentiation programme during tumour suppression
in vivo through direct DNA binding, chromatin remodelling and induction of genes
characteristic of AT1 cells. Single-cell transcriptomics analyses revealed that
during LUAD evolution, p53 promotes AT1 differentiation through action in a
transitional cell state analogous to a transient intermediary seen during
AT2-to-AT1 cell differentiation in alveolar injury repair. Notably, p53
inactivation results in the inappropriate persistence of these transitional
cancer cells accompanied by upregulated growth signalling and divergence from
lung lineage identity, characteristics associated with LUAD progression.
Analysis of Trp53 wild-type and Trp53-null mice showed that p53 also directs
alveolar regeneration after injury by regulating AT2 cell self-renewal and
promoting transitional cell differentiation into AT1 cells. Collectively, these
findings illuminate mechanisms of p53-mediated LUAD suppression, in which p53
governs alveolar differentiation, and suggest that tumour suppression reflects a
fundamental role of p53 in orchestrating tissue repair after injury.
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
DOI: 10.1038/s41586-023-06253-8
PMID: 37468633 [Indexed for MEDLINE]
3. Lancet. 2023 Aug 5;402(10400):451-463. doi: 10.1016/S0140-6736(23)00774-2. Epub 2023 Jul 6.
First-line atezolizumab monotherapy versus single-agent chemotherapy in patients
with non-small-cell lung cancer ineligible for treatment with a
platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label,
randomised controlled study.
Lee SM(1), Schulz C(2), Prabhash K(3), Kowalski D(4), Szczesna A(5), Han B(6),
Rittmeyer A(7), Talbot T(8), Vicente D(9), Califano R(10), Cortinovis D(11), Le
AT(12), Huang D(13), Liu G(14), Cappuzzo F(15), Reyes Contreras J(16), Reck
M(17), Palmero R(18), Mak MP(19), Hu Y(20), Morris S(20), Höglander E(20),
Connors M(21), Biggane AM(22), Vollan HK(20), Peters S(23).
Author information:
(1)Department of Oncology, University College London Hospitals NHS Foundation
Trust, CRUK Lung Cancer Centre of Excellence and UCL Cancer Institute, London,
UK. Electronic address: sm.lee@nhs.net.
(2)Bereich Pneumologie Klinik und Poliklinik für Innere Medizin II, University
Hospital Regensburg, Regensburg, Germany.
(3)Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.
…
Erratum in
Lancet. 2023 Aug 5;402(10400):450.
Comment in
Lancet. 2023 Aug 5;402(10400):426-427.
BACKGROUND: Despite immunotherapy advancements for patients with advanced or
metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were
limited to patients with an Eastern Cooperative Oncology Group performance
status (ECOG PS) 0-1 and a median age of 65 years or younger. We aimed to
compare the efficacy and safety of first-line atezolizumab monotherapy with
single-agent chemotherapy in patients ineligible for platinum-based
chemotherapy.
METHODS: This trial was a phase 3, open-label, randomised controlled study
conducted at 91 sites in 23 countries across Asia, Europe, North America, and
South America. Eligible patients had stage IIIB or IV NSCLC in whom
platinum-doublet chemotherapy was deemed unsuitable by the investigator due to
an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0-1
with substantial comorbidities or contraindications for platinum-doublet
chemotherapy. Patients were randomised 2:1 by permuted-block randomisation
(block size of six) to receive 1200 mg of atezolizumab given intravenously every
3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or
gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly
cycles. The primary endpoint was overall survival assessed in the
intention-to-treat population. Safety analyses were conducted in the
safety-evaluable population, which included all randomised patients who received
any amount of atezolizumab or chemotherapy. This trial is registered with
ClinicalTrials.gov, NCT03191786.
FINDINGS: Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled
and randomised to receive atezolizumab (n=302) or chemotherapy (n=151).
Atezolizumab improved overall survival compared with chemotherapy (median
overall survival 10·3 months [95% CI 9·4-11·9] vs 9·2 months [5·9-11·2];
stratified hazard ratio 0·78 [0·63-0·97], p=0·028), with a 2-year survival rate of 24%
(95% CI 19·3-29·4) with atezolizumab compared with 12% (6·7-18·0) with chemotherapy.
Compared with chemotherapy, atezolizumab was associated with
stabilisation or improvement of patient-reported health-related quality-of-life
functioning scales and symptoms and fewer grade 3-4 treatment-related adverse
events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three
[1%] vs four [3%]).
INTERPRETATION: First-line treatment with atezolizumab monotherapy was
associated with improved overall survival, a doubling of the 2-year survival
rate, maintenance of quality of life, and a favourable safety profile compared
with single-agent chemotherapy. These data support atezolizumab monotherapy as a
potential first-line treatment option for patients with advanced NSCLC who are
ineligible for platinum-based chemotherapy.
FUNDING: F Hoffmann-La Roche and Genentech Inc, a member of the Roche group.
Copyright © 2023 Elsevier Ltd. All rights reserved.
DOI: 10.1016/S0140-6736(23)00774-2
PMID: 37423228 [Indexed for MEDLINE]
4. Nature. 2023 Aug;620(7973):393-401. doi: 10.1038/s41586-023-06303-1. Epub 2023
Jul 5.
Therapy-induced APOBEC3A drives evolution of persistent cancer cells.
Isozaki H(1)(2), Sakhtemani R(3)(4), Abbasi A(3), Nikpour N(3), Stanzione M(3),
Oh S(5), Langenbucher A(3), Monroe S(3), Su W(3),…
Author information:
(1)Massachusetts General Hospital Cancer Center, Boston, MA, USA.
hisozaki@mgh.harvard.edu.
(2)Department of Medicine, Massachusetts General Hospital and Harvard Medical
School, Boston, MA, USA. hisozaki@mgh.harvard.edu.
(3)Massachusetts General Hospital Cancer Center, Boston, MA, USA.
…
Acquired drug resistance to anticancer targeted therapies remains an unsolved
clinical problem. Although many drivers of acquired drug resistance have been
identified1-4, the underlying molecular mechanisms shaping tumour evolution
during treatment are incompletely understood. Genomic profiling of patient
tumours has implicated apolipoprotein B messenger RNA editing catalytic
polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however,
their role during therapy and the development of acquired drug resistance is
undefined. Here we report that lung cancer targeted therapies commonly used in
the clinic can induce cytidine deaminase APOBEC3A (A3A), leading to sustained
mutagenesis in drug-tolerant cancer cells persisting during therapy.
Therapy-induced A3A promotes the formation of double-strand DNA breaks,
increasing genomic instability in drug-tolerant persisters. Deletion of A3A
reduces APOBEC mutations and structural variations in persister cells and delays
the development of drug resistance. APOBEC mutational signatures are enriched in
tumours from patients with lung cancer who progressed after extended responses
to targeted therapies. This study shows that induction of A3A in response to
targeted therapies drives evolution of drug-tolerant persister cells, suggesting
that suppression of A3A expression or activity may represent a potential
therapeutic strategy in the prevention or delay of acquired resistance to lung
cancer targeted therapy.
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
DOI: 10.1038/s41586-023-06303-1
PMID: 37407818 [Indexed for MEDLINE]
5. N Engl J Med. 2023 Jul 13;389(2):137-147. doi: 10.1056/NEJMoa2304594. Epub 2023 Jun 4.
Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.
Tsuboi M(1), Herbst RS(1), John T(1), Kato T(1), Majem M(1), Grohé C(1), Wang
J(1), Goldman JW(1), Lu S(1), Su WC(1), de Marinis F(1), Shepherd FA(1), Lee
KH(1), Le NT(1), Dechaphunkul A(1), Kowalski D(1), Poole L(1), Bolanos A(1),
Rukazenkov Y(1), Wu YL(1); ADAURA Investigators.
Author information:
(1)From the Department of Thoracic Surgery and Oncology, National Cancer Center
Hospital East, Kashiwa (M.T.), the Department of Thoracic Oncology, Kanagawa
Cancer Center, Yokohama (T.K.) - both in Japan; the Section of Medical Oncology,
Yale School of Medicine and Yale Cancer Center, New Haven, CT (R.S.H.); the
Department of Medical Oncology, Peter MacCallum Cancer Centre, and the Sir Peter
MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC,
Australia (T.J.); the Department of Medical Oncology, Hospital de la Santa Creu
i Sant Pau, Barcelona (M.M.); …
BACKGROUND: Among patients with resected, epidermal growth factor receptor
(EGFR)-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant
osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in
significantly longer disease-free survival than placebo in the ADAURA trial. We
report the results of the planned final analysis of overall survival.
METHODS: In this phase 3, double-blind trial, we randomly assigned eligible
patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo
until disease recurrence was observed, the trial regimen was completed (3
years), or a discontinuation criterion was met. The primary end point was
investigator-assessed disease-free survival among patients with stage II to IIIA
disease. Secondary end points included disease-free survival among patients with
stage IB to IIIA disease, overall survival, and safety.
RESULTS: Of 682 patients who underwent randomization, 339 received osimertinib
and 343 received placebo. Among patients with stage II to IIIA disease, the
5-year overall survival was 85% in the osimertinib group and 73% in the placebo
group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI],
0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to
IIIA disease), the 5-year overall survival was 88% in the osimertinib group and
78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34
to 0.70; P<0.001). One new serious adverse event, pneumonia related to
coronavirus disease 2019, was reported after the previously published
data-cutoff date (the event was not considered by the investigator to be related
to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had
a safety profile consistent with that in the primary analysis.
CONCLUSIONS: Adjuvant osimertinib provided a significant overall survival
benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA
NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).
Copyright © 2023 Massachusetts Medical Society.
DOI: 10.1056/NEJMoa2304594
PMID: 37272535 [Indexed for MEDLINE]
6. CA Cancer J Clin. 2023 Jul-Aug;73(4):358-375. doi: 10.3322/caac.21774. Epub 2023 Mar 1.
Acquiring tissue for advanced lung cancer diagnosis and comprehensive biomarker
testing: A National Lung Cancer Roundtable best-practice guide.
Fox AH(1), Nishino M(2)(3), Osarogiagbon RU(4), Rivera MP(5), Rosenthal LS(6),
Smith RA(6), Farjah F(7), Sholl LM(8), Silvestri GA(1), Johnson BE(9).
Author information:
(1)Division of Pulmonary Critical Care, Allergy and Sleep Medicine, Medical
University of South Carolina, Charleston, South Carolina, USA.
(2)Department of Imaging, Dana-Farber Cancer Institute, Boston, Massachusetts,
USA.
(3)Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts,
USA.
…
Advances in biomarker-driven therapies for patients with nonsmall cell lung
cancer (NSCLC) both provide opportunities to improve the treatment (and thus
outcomes) for patients and pose new challenges for equitable care delivery. Over
the last decade, the continuing development of new biomarker-driven therapies
and evolving indications for their use have intensified the importance of
interdisciplinary communication and coordination for patients with or suspected
to have lung cancer. Multidisciplinary teams are challenged with completing
comprehensive and timely biomarker testing and navigating the constantly
evolving evidence base for a complex and time-sensitive disease. This guide
provides context for the current state of comprehensive biomarker testing for
NSCLC, reviews how biomarker testing integrates within the diagnostic continuum
for patients, and illustrates best practices and common pitfalls that influence
the success and timeliness of biomarker testing using a series of case
scenarios.
© 2023 The Authors. CA: A Cancer Journal for Clinicians published by Wiley
Periodicals LLC on behalf of American Cancer Society.
DOI: 10.3322/caac.21774
PMID: 36859638 [Indexed for MEDLINE]
7. Nat Med. 2023 Jul;29(7):1718-1727. doi: 10.1038/s41591-023-02385-6. Epub 2023
Jul 10.
Biomarker-directed, pembrolizumab-based combination therapy in non-small cell
lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results.
Gutierrez M(1), Lam WS(2), Hellmann MD(3)(4), Gubens MA(5), Aggarwal C(6), Tan
DSW(7), Felip E(8), Chiu JWY(9), Lee JS(10), Yang JC(11), Garon EB(12),
Finocchiaro G(13), Ahn MJ(14), Luft A(15), Landers GA(16), Basso A(17), Ma
H(17)(18), Kobie J(17), Palcza J(17), Cristescu R(17), Fong L(5), Snyder
A(17)(19), Yuan J(17), Herbst RS(20).
Author information:
(1)Hackensack University Medical Center, Hackensack, NJ, USA.
martin.gutierrez@hmhn.org.
(2)Fiona Stanley Hospital and Western Australia Country Health Service, Perth,
WA, Australia.
(3)Memorial Sloan Kettering Cancer Center, New York, NY, USA.
…
Although pembrolizumab confers clinical benefit in non-small cell lung cancer
(NSCLC), only a subset of patients will respond due to a heterogenous tumor
microenvironment. KEYNOTE-495/KeyImPaCT is an ongoing biomarker-directed,
adaptively randomized phase 2 study investigating first-line pembrolizumab
(200 mg every 3 weeks) + lenvatinib (20 mg daily), anti-CTLA-4 quavonlimab
(25 mg every 6 weeks) or anti-LAG-3 favezelimab (200 mg or 800 mg every 3 weeks)
in advanced NSCLC. Patients were categorized by T-cell-inflamed gene expression
profile (TcellinfGEP) and tumor mutational burden (TMB) status and randomly
assigned 1:1:1 to receive pembrolizumab + lenvatinib, pembrolizumab +
quavonlimab or pembrolizumab + favezelimab. The primary outcome was
investigator-assessed objective response rate (ORR) per Response Evaluation
Criteria in Solid Tumors version 1.1 using pre-specified efficacy thresholds for
each biomarker-defined subgroup (>5% (TcellinfGEPlowTMBnon-high (group I)), >20%
(TcellinfGEPlowTMBhigh (group II) and TcellinfGEPnon-lowTMBnon-high (group III))
and >45% (TcellinfGEPnon-lowTMBhigh (group IV))). Secondary outcomes were
progression-free survival, overall survival and safety. At data cutoff, ORR
ranges were 0-12.0% in group I, 27.3-33.3% in group II, 13.6-40.9% in group III
and 50.0-60.0% in group IV. ORR with pembrolizumab + lenvatinib in group III met
the pre-specified efficacy threshold. The safety profile of each treatment arm
was consistent with the known safety profile of each combination. These data
demonstrate the feasibility of prospective TcellinfGEP and TMB assessment to
study the clinical activity of first-line pembrolizumab-based combination
therapies in advanced NSCLC. ClinicalTrials.gov registration: NCT03516981 .
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
DOI: 10.1038/s41591-023-02385-6
PMID: 37429923 [Indexed for MEDLINE]
8. J Clin Oncol. 2023 Jul 20:JCO2301261. doi: 10.1200/JCO.23.01261. Online ahead of print.
Management of Stage III Non-Small-Cell Lung Cancer: ASCO Guideline Rapid
Recommendation Update.
Singh N(1), Daly ME(2), Ismaila N(3); Management of Stage III NSCLC Guideline
Expert Panel.
Author information:
(1)Postgraduate Institute of Medical Education & Research, Chandigarh, India.
(2)University of California Davis Comprehensive Cancer Center, Sacramento, CA.
(3)American Society of Clinical Oncology, Alexandria, VA.
ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline
recommendations as a response to the emergence of new and practice-changing
data. The rapid updates are supported by an evidence review and follow the
guideline development processes outlined in the ASCO Guideline Methodology
Manual. The goal of these articles is to disseminate updated recommendations, in
a timely manner, to better inform health practitioners and the public on the
best available cancer care options. See the Appendix for disclaimers and other
important information (Appendix 1 and Appendix 2, online only).
DOI: 10.1200/JCO.23.01261
PMID: 37471673
9. Nat Commun. 2023 Jul 15;14(1):4238. doi: 10.1038/s41467-023-39874-8.
Impact of TMB/PD-L1 expression and pneumonitis on chemoradiation and durvalumab
response in stage III NSCLC.
Alessi JV(1), Ricciuti B(1), Wang X(2), Pecci F(1), Di Federico A(1), Lamberti
G(1), Elkrief A(3)(4)(5), Rodig SJ(6)(7), Lebow ES(8), Eicholz JE(3), Thor M(9),
Rimner A(8), Schoenfeld AJ(3), Chaft JE(3), Johnson BE(1), Gomez DR(8), Awad
MM(1), Shaverdian N(10).
Author information:
(1)Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA,
USA.
(2)Department of Environmental Health, Harvard T.H. Chan School of Public
Health, Harvard University, Boston, MA, USA.
(3)Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York,
NY, USA.
…
Although concurrent chemoradiation (CRT) and durvalumab consolidation has become
a standard treatment for stage III non-small cell lung cancer (NSCLC),
clinicopathologic and genomic factors associated with its efficacy remain poorly
characterized. Here, in a multi-institutional retrospective cohort study of 328
patients treated with CRT and durvalumab, we identify that very high PD-L1 tumor
proportion score (TPS) expression ( ≥ 90%) and increased tumor mutational burden
(TMB) are independently associated with prolonged disease control. Additionally,
we identify the impact of pneumonitis and its timing on disease outcomes among
patients who discontinue durvalumab: compared to patients who experienced
early-onset pneumonitis ( < 3 months) leading to durvalumab discontinuation,
patients with late-onset pneumonitis had a significantly longer PFS (12.7 months
vs not reached; HR 0.24 [95% CI, 0.10 to 0.58]; P = 0.001) and overall survival
(37.2 months vs not reached; HR 0.26 [95% CI, 0.09 to 0.79]; P = 0.017). These
findings suggest that opportunities exist to improve outcomes in patients with
lower PD-L1 and TMB levels, and those at highest risk for pneumonitis.
© 2023. The Author(s).
DOI: 10.1038/s41467-023-39874-8
PMCID: PMC10349822
PMID: 37454214 [Indexed for MEDLINE]
10. J Clin Oncol. 2023 Aug 20;41(24):e63-e72. doi: 10.1200/JCO.23.01055. Epub 2023 Jul 11.
Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO
Living Guideline, Version 2023.2.
Owen DH(1), Singh N(2), Ismaila N(3), Masters G(4), Riely GJ(5), Robinson AG(6),
Schneider BJ(7), Jaiyesimi IA(8).
Author information:
(1)Ohio State University, Columbus OH.
(2)Postgraduate Institute of Medical Education and Research, Chandigarh, India.
(3)American Society of Clinical Oncology, Alexandria, VA.
(4)Helen F. Graham Cancer Center and Research Institute, Newark, DE.
(5)Memorial Sloan Kettering Cancer Center, New York, NY.
(6)Kingston General Hospital, Queen's University, Ontario, Canada.
(7)University of Michigan Health System, Ann Arbor, MI.
(8)Corewell Health William Beaumont University Hospital Royal Oak and Oakland
University William Beaumont School of Medicine, Rochester, MI.
Update of
J Clin Oncol. 2022 Oct 1;40(28):3310-3322.
Living guidelines are developed for selected topic areas with rapidly evolving
evidence that drives frequent change in clinical practice. Living guidelines are
updated on a regular schedule by a standing expert panel that systematically
reviews the health literature on a continuous basis; as described in the ASCO
Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict
of Interest Policy Implementation for Clinical Practice Guidelines. Living
Guidelines and updates are not intended to substitute for independent
professional judgment of the treating provider and do not account for individual
variation among patients. See appendix for disclaimers and other important
information (Appendix 1 and Appendix 2). Updates are published regularly and can
be found at https://ascopubs.org/nsclc-da-living-guideline.
DOI: 10.1200/JCO.23.01055
PMID: 37433095 [Indexed for MEDLINE]
11. PLoS Med. 2023 Jul 11;20(7):e1004252. doi: 10.1371/journal.pmed.1004252.
eCollection 2023 Jul.
The potential impact of novel tuberculosis vaccine introduction on economic
growth in low- and middle-income countries: A modeling study.
Portnoy A(1)(2), Arcand JL(3)(4)(5)(6), Clark RA(7)(8)(9), Weerasuriya
CK(7)(8)(9), Mukandavire C(10), Bakker R(7)(8)(9)(11), Patouillard E(12),
Gebreselassie N(13), Zignol M(13), Jit M(8)(9)(14), White RG(7)(8)(9), Menzies
NA(2)(15).
Author information:
(1)Department of Global Health, Boston University School of Public Health,
Boston, Massachusetts, United States of America.
(2)Center for Health Decision Science, Harvard T.H. Chan School of Public
Health, Boston, Massachusetts, United States of America.
(3)Department of International Economics, The Graduate Institute of
International and Development Studies, Geneva, Switzerland.
…
BACKGROUND: Most individuals developing tuberculosis (TB) are working age adults
living in low- and middle-income countries (LMICs). The resulting disability and
death impact economic productivity and burden health systems. New TB vaccine
products may reduce this burden. In this study, we estimated the impact of
introducing novel TB vaccines on gross domestic product (GDP) growth in 105
LMICs.
METHODS AND FINDINGS: We adapted an existing macroeconomic model to simulate
country-level GDP trends between 2020 and 2080, comparing scenarios for
introduction of hypothetical infant and adolescent/adult vaccines to a
no-new-vaccine counterfactual. We parameterized each scenario using estimates of
TB-related mortality, morbidity, and healthcare spending from linked
epidemiological and costing models. We assumed vaccines would be introduced
between 2028 and 2047 and estimated incremental changes in GDP within each
country from introduction to 2080, in 2020 US dollars. We tested the robustness
of results to alternative analytic specifications. Both vaccine scenarios
produced greater cumulative GDP in the modeled countries over the study period,
equivalent to $1.6 (95% uncertainty interval: $0.8, 3.0) trillion for the
adolescent/adult vaccine and $0.2 ($0.1, 0.4) trillion for the infant vaccine.
These GDP gains were substantially lagged relative to the time of vaccine
introduction, particularly for the infant vaccine. GDP gains resulting from
vaccine introduction were concentrated in countries with higher current TB
incidence and earlier vaccine introduction. Results were sensitive to secular
trends in GDP growth but relatively robust to other analytic assumptions.
Uncertain projections of GDP could alter these projections and affect the
conclusions drawn by this analysis.
CONCLUSIONS: Under a range of assumptions, introducing novel TB vaccines would
increase economic growth in LMICs.
Copyright: © 2023 Portnoy et al. This is an open access article distributed
under the Creative Commons Attribution IGO License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work is
properly cited. https://creativecommons.org/licenses/by/3.0/igo/. In any use of
this article, there should be no suggestion that WHO endorses any specific
organization, products or services. The use of the WHO logo is not permitted.
This notice should be preserved along with the article’s original URL.
DOI: 10.1371/journal.pmed.1004252
PMCID: PMC10335702
PMID: 37432972 [Indexed for MEDLINE]
12. Am J Respir Crit Care Med. 2023 Jul 15;208(2):130-131. doi:
10.1164/rccm.202304-0670VP.
Making the Case for All-Oral, Shorter Regimens for Children with Drug-Resistant
Tuberculosis.
Patankar S(1), Cruz AT(2), Douglas-Jones B(3), Garcia-Prats A(3)(4), Kay A(2),
Reuter A(5), Schaaf HS(3), Seddon JA(3)(6), Sharma S(7), Starke J(2), Tommasi
M(8), Triasih R(9), Furin JJ(10).
Author information:
(1)College of Arts and Sciences, Harvard University, Cambridge, Massachusetts.
(2)Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
(3)Faculty of Medicine and Health Sciences, Department of Pediatrics and Child
Health, Desmond Tutu TB Centre, Stellenbosch University, Cape Town, South
Africa.
…
DOI: 10.1164/rccm.202304-0670VP
PMCID: PMC10395497
PMID: 37276531 [Indexed for MEDLINE]
13. Lancet Infect Dis. 2023 Jul;23(7):778-780. doi: 10.1016/S1473-3099(23)00349-3. Epub 2023 May 25.
Children deserve simple, short, safe, and effective treatment for
rifampicin-resistant tuberculosis.
Garcia-Prats AJ(1), Hoddinott G(2), Howell P(3), Hughes J(2), Jean-Philippe
P(4), Kim S(5), Palmer M(2), Schaaf HS(2), Seddon JA(6), Svensson E(7),
Hesseling AC(2).
Author information:
(1)Department of Pediatrics, School of Medicine and Public Health, University of
Wisconsin-Madison, Madison, WI 53705, USA; Desmond Tutu TB Centre, Department of
Paediatics and Child Health, Faculty of Medicine and Health Sciences,
Stellenbosch University, Cape Town, South Africa. Electronic address:
garciaprats@wisc.edu.
(2)Desmond Tutu TB Centre, Department of Paediatics and Child Health, Faculty of
Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
(3)Clinical HIV Research Unit, Sizwe Tropical Disease Hospital, Wits Health
Consortium, Department of Internal Medicine, University of the Witwatersrand,
Johannesburg, South Africa.
(4)National Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, MD, USA.
(5)Department of Biostatistics, Frontier Science Foundation, Brookline, MA, USA.
(6)Desmond Tutu TB Centre, Department of Paediatics and Child Health, Faculty of
Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa;
Department of Infectious Disease, Imperial College London, London, UK.
(7)Department of Pharmacy, Uppsala University, Uppsala, Sweden; Department of
Pharmacy, Research Institute for Medical Innovation, Radboud University Medical
Center, Radboud University, Nijmegen, Netherlands.
DOI: 10.1016/S1473-3099(23)00349-3
PMID: 37245523 [Indexed for MEDLINE]
14. J Clin Invest. 2023 Jul 3;133(13):e167762. doi: 10.1172/JCI167762.
Host genetic background is a barrier to broadly effective vaccine-mediated
protection against tuberculosis.
Lai R(1), Gong DN(2), Williams T(1), Ogunsola AF(1), Cavallo K(1), Lindestam
Arlehamn CS(3), Acolatse S(2), Beamer GL(4), Ferris MT(5), Sassetti CM(1),
Lauffenburger DA(2), Behar SM(1).
Author information:
(1)Department of Microbiology and Physiological Systems, University of
Massachusetts Medical School, Worcester, Massachusetts, USA.
(2)Department of Biological Engineering, Massachusetts Institute of Technology,
Cambridge, Massachusetts, USA.
(3)Center for infectious disease and vaccine research, La Jolla Institute for
Immunology, La Jolla, California, USA.
(4)Texas Biomedical Research Institute, San Antonio, Texas, USA.
(5)Department of Genetics, University of North Carolina at Chapel Hill, Chapel
Hill, North Carolina, USA.
Heterogeneity in human immune responses is difficult to model in standard
laboratory mice. To understand how host variation affects Bacillus Calmette
Guerin-induced (BCG-induced) immunity against Mycobacterium tuberculosis, we
studied 24 unique collaborative cross (CC) mouse strains, which differ primarily
in the genes and alleles they inherit from founder strains. The CC strains were
vaccinated with or without BCG and challenged with aerosolized M. tuberculosis.
Since BCG protects only half of the CC strains tested, we concluded that host
genetics has a major influence on BCG-induced immunity against M. tuberculosis
infection, making it an important barrier to vaccine-mediated protection.
Importantly, BCG efficacy is dissociable from inherent susceptibility to
tuberculosis (TB). T cell immunity was extensively characterized to identify
components associated with protection that were stimulated by BCG and recalled
after M. tuberculosis infection. Although considerable diversity is observed,
BCG has little impact on the composition of T cells in the lung after infection.
Instead, variability is largely shaped by host genetics. BCG-elicited protection
against TB correlated with changes in immune function. Thus, CC mice can be used
to define correlates of protection and to identify vaccine strategies that
protect a larger fraction of genetically diverse individuals instead of
optimizing protection for a single genotype.
DOI: 10.1172/JCI167762
PMCID: PMC10313364
PMID: 37200108 [Indexed for MEDLINE]
15. Lancet Infect Dis. 2023 Jul;23(7):847-855. doi: 10.1016/S1473-3099(23)00067-1. Epub 2023 Mar 23.
Rosuvastatin adjunctive therapy for rifampicin-susceptible pulmonary
tuberculosis: a phase 2b, randomised, open-label, multicentre trial.
Cross GB(1), Sari IP(2), Kityo C(3), Lu Q(4), Pokharkar Y(4), Moorakonda RB(4),
Thi HN(5), Do Q(5), Dalay VB(6), Gutierrez E(6), Balanag VM(7), Castillo RJ(7),
Mugerwa H(3), Fanusi F(8), Kwan P(8), Chew KL(9), Paton NI(10); ROSETTA trial
team.
Author information:
(1)Infectious Disease Translational Research Programme, National University of
Singapore, Singapore; Department of Medicine, National University Health
Systems, Singapore. Electronic address: gail.cross@burnet.edu.au.
(2)Department of Medicine, National University Health Systems, Singapore.
(3)Joint Clinical Research Centre, Kampala, Uganda.
…
BACKGROUND: Shorter treatments are needed for drug-susceptible tuberculosis.
Adjunctive statins increase bactericidal activity in preclinical tuberculosis
models. We investigated the safety and efficacy of adjunctive rosuvastatin in
people with tuberculosis. We tested the hypothesis that adjunctive rosuvastatin
accelerates sputum culture conversion within the first 8 weeks of treatment of
rifampicin-susceptible tuberculosis.
METHODS: This phase 2b, randomised, open-label, multicentre trial conducted in
five hospitals or clinics in three countries with high tuberculosis burden (ie,
the Philippines, Viet Nam, and Uganda) enrolled adult participants aged 18-75
years with sputum smear or Xpert MTB/RIF positive, rifampicin-susceptible
tuberculosis who had received less than 7 days of previous tuberculosis
treatment. Participants were randomly assigned via a web-based system to receive
either 10 mg rosuvastatin once per day for 8 weeks plus standard tuberculosis
therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol; rosuvastatin
group) or standard tuberculosis therapy alone (control group). Randomisation was
stratified by trial site, history of diabetes, and HIV co-infection. Laboratory
staff and central investigators involved in data cleaning and analysis were
masked to treatment allocation, but study participants and site investigators
were not. Both groups continued standard treatment to week 24. Sputum samples
were collected once per week for the first 8 weeks after randomisation, and then
at weeks 10, 12, and 24. The primary efficacy outcome was time to culture
conversion (TTCC; days) in liquid culture by week 8, assessed in randomised
participants who had microbiological confirmation of tuberculosis, took at least
one dose of rosuvastatin, and who did not show resistance to rifampicin
(modified intention-to-treat population), for which groups were compared with
the Cox proportional hazards model. The main safety outcome was grade 3-5
adverse events by week 24, assessed in the intention-to-treat population, for
which groups were compared with Fisher's exact test. All participants completed
24 weeks of follow-up. This trial is registered with ClinicalTrials.gov
(NCT04504851).
FINDINGS: Between Sept 2, 2020, and Jan 14, 2021, 174 participants were screened
and 137 were randomly assigned to the rosuvastatin group (70 participants) or
control group (67 participants). In the modified intention-to-treat population
of 135 participants, 102 (76%) were men and 33 (24%) were women. Median TTCC in
liquid media was 42 days (95% CI 35-49) in the rosuvastatin group (68
participants) and 42 days (36-53) in the control group (67 participants; hazard
ratio 1·30 [0·88-1·91], p=0·19). Grade 3-5 adverse events occurred in six (9%)
of 70 in the rosuvastatin group (none were considered related to rosuvastatin)
and four (6%) of 67 in the control group (p=0·75). There were no serious adverse
events that were considered to be related to rosuvastatin.
INTERPRETATION: Adjunctive rosuvastatin at 10 mg once per day was safe but did
not produce substantive benefits on culture conversion in the overall study
population. Future trials could explore the safety and efficacy of higher doses
of adjunctive rosuvastatin.
FUNDING: National Medical Research Council, Singapore.
Copyright © 2023 Elsevier Ltd. All rights reserved.
DOI: 10.1016/S1473-3099(23)00067-1
PMID: 36966799 [Indexed for MEDLINE]
