Exploratory Evaluation of Bezlotoxumab on Outcomes Associated With Clostridioides difficile Infection in MODIFY I/II Participants With Cancer

Abstract

Background: The incidence of Clostridioides difficile infection (CDI) is reportedly higher and the cure rate lower in individuals with cancer vs those without cancer. An exploratory post hoc analysis of the MODIFY I/II trials (NCT01241552/NCT01513239) investigated how bezlotoxumab affected the rate of CDI-related outcomes in participants with cancer.

Methods: Participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI antibacterial treatment. A post hoc analysis of CDI-related outcomes was conducted in subgroups of MODIFY I/II participants with and without cancer.

Results: Of 1554 participants in the modified intent-to-treat (mITT) population, 382 (24.6%) were diagnosed with cancer (bezlotoxumab 190, placebo 192). Of participants without cancer, 591 and 581 received bezlotoxumab and placebo, respectively. In the placebo group, initial clinical cure (ICC) was achieved by fewer cancer participants vs participants without cancer (71.9% vs 83.1%; absolute difference, -11.3%; 95% CI, -18.6% to -4.5%); however, CDI recurrence (rCDI) rates were similar in cancer (30.4%) and noncancer (34.0%) participants. In participants with cancer, bezlotoxumab treatment had no effect on ICC rate compared with placebo (76.8% vs 71.9%), but resulted in a statistically significant reduction in rCDI vs placebo (17.8% vs 30.4%; absolute difference, -12.6%; 95% CI, -22.5% to -2.7%).

Conclusions: In this post hoc analysis of participants with cancer enrolled in MODIFY I/II, the rate of rCDI in bezlotoxumab-treated participants was lower than in placebo-treated participants. Additional studies are needed to confirm these results.

Clinical trial registration: MODIFY I (NCT01241552), MODIFY II (NCT01513239).

Keywords: CDI recurrence; Clostridioides difficile; cancer; hematologic malignancy; solid tumor.

Figure 1.

Proportion of participants with ICC, rCDI, and SCC stratified by treatment group in participants (A) with a cancer diagnosis and (B) without a cancer diagnosis. Abbreviations: CDI, Clostridioides difficile infection; CI, confidence interval; ICC, initial clinical cure; rCDI, recurrent Clostridioides difficile infection; SCC, sustained clinical cure.

Figure 2.

Time to rCDI stratified using the log-rank test by treatment group in participants with and without a cancer diagnosis (mITT population). The start date of rCDI was defined as the first day of a new episode of diarrhea. Time to event was right-censored at the date of the last stool record for any participants who were lost to follow-up before recurrence of CDI. Participants who completed the 12-week follow-up period without any reported episode of rCDI were censored at the date of the last completed stool record. For any participants who failed to achieve ICC for the baseline C. difficile episode, time to event was right-censored at the date of infusion of study medication. Abbreviations: CDI, Clostridioides difficile infection; CI, confidence interval; ICC, initial clinical cure; KM, Kaplan-Meier; mITT, modified intent-to-treat; rCDI, recurrent Clostridioides difficile infection.

Figure 3.

Proportion of participants with CDI-associated readmissions within 30 days of hospital discharge (among those hospitalized at the time of randomization). Abbreviations: CDI, Clostridioides difficile infection; CI, confidence interval.