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Interesting study about checkpoint inhibitors

LisaPizza's picture
LisaPizza
Posts: 218
Joined: Feb 2018

This is just a preliminary study, but interesting. Checkpoint inhibitors include Keytruda (pembrolizumab).

 

https://jamanetwork.com/journals/jamaoncology/article-abstract/2749683

 

Audio Interview(14:39)
Association of Prior Antibiotic Treatment With Survival and Response to Immune Checkpoint Inhibitor Therapy in Patients With Cancer
Key Points

Question  Does broad-spectrum antibiotic treatment alter responsive to immune checkpoint inhibitors (ICIs) in routine practice?

Findings  In this observational study that included 196 patients with cancer treated with ICI therapy, antibiotic treatment administered within 30 days from commencement of ICI therapy was associated with significantly worse overall survival and a higher risk of disease refractory to treatment.

Meaning  Antibiotic therapy is associated with a reduced response to ICIs in routine practice, irrespective of tumor site; mechanistic studies exploring this relationship are warranted.

Abstract

Importance  Gut dysbiosis impairs response to immune checkpoint inhibitors (ICIs) and can be caused by broad-spectrum antibiotic (ATB) therapy.

Objective  To evaluate whether there is an association between ATB therapy administered concurrently (cATB) or prior (pATB) to ICI therapy and overall survival (OS) and treatment response to ICI therapy in patients with cancer treated with ICIs in routine clinical practice.

Design, Setting, and Participants  This prospective, multicenter, cohort study conducted at 2 tertiary academic referral centers recruited 196 patients with cancer who received ICI therapy between January 1, 2015, and April 1, 2018, in routine clinical practice rather than clinical trials.

Main Outcomes and Measures  Overall survival calculated from the time of ICI therapy commencement and radiologic response to ICI treatment defined using the Response Evaluation Criteria in Solid Tumors (version 1.1), with disease refractory to ICI therapy defined as progressive disease 6 to 8 weeks after the first ICI dose without evidence of pseudoprogression.

Results  Among 196 patients (137 men and 59 women; median [range] age, 68 [27-93] years) with non–small cell lung cancer (n = 119), melanoma (n = 38), and other tumor types (n = 39), pATB therapy (HR, 7.4; 95% CI, 4.3-12.8; P < .001), but not cATB therapy (HR, 0.9; 95% CI, 0.5-1.4; P = .76), was associated with worse OS (2 vs 26 months for pATB therapy vs no pATB therapy, respectively) (hazard ratio [HR], 7.4; 95% CI, 4.2-12.9) and a higher likelihood of primary disease refractory to ICI therapy (21 of 26 [81%] vs 66 of 151 [44%], P < .001). Overall survival in patients with non–small cell lung cancer (2.5 vs 26 months, P < .001), melanoma (3.9 vs 14 months, P < .001), and other tumor types (1.1 vs 11, P < .001) was consistently worse in those who received pATBs vs those who did not. Multivariate analyses confirmed that pATB therapy (HR, 3.4; 95% CI, 1.9-6.1; P < .001) and response to ICI therapy (HR, 8.2; 95% CI, 4.0-16.9; P < .001) were associated with OS independent of tumor site, disease burden, and performance status.

Conclusions and Relevance  Despite being limited by sample size, geographic origin, and the lack of correlative analyses on patients’ gut microbiota, this study suggests that pATB therapy but not cATB therapy is associated with a worse treatment response and OS in unselected patients treated with ICIs in routine clinical practice. Mechanistic studies are urgently required to investigate ATB-mediated alterations of gut microbiota as a determinant of poorer outcome following ICI treatment.

 

 

 

Armywife's picture
Armywife
Posts: 313
Joined: Feb 2018

This is fascinating!  I wonder if the "prior" means ever having received antibiotics.  I can't imagine there are too many of us around who haven't at some point.

LisaPizza's picture
LisaPizza
Posts: 218
Joined: Feb 2018

Prior was within the last 30 days. 

Fridays Child
Posts: 67
Joined: Jul 2019

Very interesting article.

Northwoodsgirl
Posts: 536
Joined: Oct 2009

Very interesting observational study. The thing I found interesting was the importance of the timing of anitibiotic therapy in relation to survival using immune therapy. Thirty days before made a difference but if on antibiotics during the immunotherapy difference not observed in terms of survival. Lots more rigorous types of studies need yet to be done. Our gut health is fascinating in its relationship to our over all health. Thank you Lisa for sharing your research study article. 

Lori

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