Antibiotics don’t impair chemo-immunotherapy efficacy in lung cancer

Lung cancer

By Michael Woodhead

8 Nov 2021

While antibiotics may impair the efficacy of immune checkpoint inhibitors, the detrimental effect does not extend to chemo-immunotherapy combinations in patients with lung cancer, new research shows.

An international multicentre study involving 302 patients with stage IV NSCLC found no effect of prior (n= 47 patients) or current antibiotic therapy on the efficacy of first line chemo-immunotherapy

The study evaluated outcomes in patients treated at eight European cancer centres, mostly  with pembrolizumab and histology-based platinum doublets, though some received atezolizumab and histology-based platinum doublets or atezolizumab-bevacizumab/carboplatin-paclitaxel.

In multivariable analysis patients with prior antibiotic use had similar overall survival OS (hazard ratio = 1.42, 95% confidence interval: 0.91-2.22; P = 0.1207) and progression free survival (PFS, HR = 1.12, 95% CI: 0.76-1.63; P = 0.5552), compared to patients unexposed to antibiotics, regardless of performance status.

Similarly, no difference with respect to objective response rate  (ORR) was found with prior antibiotic exposure (42.6% versus 57.4%, P = 0.1794).

The study also found no differences in efficacy related to duration of antibiotic exposure (≥7 versus <7 days) or route of administration (intravenous versus oral).

Current antibiotic use was not associated with OS (HR = 1.29, 95% CI: 0.91-1.84; P = 0.149)] and PFS (HR = 1.20, 95% CI: 0.89-1.63; P = 0.222) in multivariable analysis, according to findings published in the Annals of Oncology.

The study investigators said prior antibiotic therapy was known to impair efficacy of single-agent immune checkpoint inhibitors, potentially through the induction of gut dysbiosis, but the effects on  chemo-immunotherapy combinations ere unknown until now.

They said the findings were clinically relevant given the synergistic efficacy of chemo-immunotherapy combinations, in NSCLC which have led to incremental survival benefit in metastatic patients.

With chemo-immunotherapy combinations now becoming a first-line option for patients with NSCLC, regardless of PD-L1 expression, the findings showed that antibiotics were not only safe, but might also influence the choice of therapy, they said.

“Based on our findings, patients with PD-L1-positive NSCLC and prior antibiotic exposure might be best served by chemo-immunotherapy combinations to avoid the detrimental effect of antibiotics,” they wrote.

“The lack of effect of [current antibiotics] on oncological outcomes suggests that prompt integration of antibiotic therapy in patients with chemotherapy-induced neutropenia and febrile neutropenia in the context of chemo-immunotherapy combinations should therefore not be delayed,” they added.

A mechanism to explain the lack of impairment of efficacy of chemo-immunotherapy with antibiotics may be related to less reliance on gut bacterial composition compared to ICI monotherapy, the researchers suggested.

Also, the detrimental effect of antibiotics might be compensated by the synergistic interaction between checkpoint inhibitors and cytotoxic chemotherapy.

“Chemotherapy-induced tumour cell lysis can in fact increase tumour antigenicity by facilitating exposure and presentation of previously inaccessible tumour antigens, whereas local and systemic release of damage-associated molecular patterns holds an important adjuvant role in augmenting adaptive immunity in conjunction with programmed cell death protein 1 blockade,” they noted.

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