Efficacy and safety of mirogabalin for chemotherapy-induced peripheral neuropathy: a prospective single-arm trial (MiroCIP study)

Abstract

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, dose-limiting adverse effect of commonly used chemotherapeutic agents. The purpose of this exploratory study was to evaluate the efficacy and safety of mirogabalin in patients with moderate to severe CIPN during chemotherapy and the effects of 12 weeks' intervention on chemotherapy completion and CIPN severity.

Methods: Patients experiencing moderate to severe CIPN while undergoing oxaliplatin- or taxane-containing chemotherapy for colorectal, gastric, non-small-cell lung, or breast cancer received mirogabalin at between 5 and 15 mg twice daily. The primary endpoint was change in numeric rating scale (NRS) score for pain from baseline to week 12. Secondary endpoints included NRS scores for tingling and sleep, completion of chemotherapy, severity of CIPN, and quality of life (QOL) scores. The safety endpoint was incidence of adverse events.

Results: Of 58 patients who consented to participation, 52 were eligible and constituted the full analysis set and safety analysis set. From baseline to week 12 (last observation carried forward [LOCF]), NRS score decreased by 30.9%: mean change (95% confidence interval [CI]), - 1.7 (- 2.4 to - 1.0) (p < 0.001). Patients with baseline NRS of ≥ 6 experienced a 44.0% reduction in score from baseline to week 12 (LOCF): mean change (95% CI), - 3.3 (- 5.0 to - 1.5) (p = 0.002). Chemotherapy was discontinued in 18 (34.6%) patients; CIPN led to discontinuation in only 2 (3.8%). There was no notable worsening of CIPN severity in terms of Common Terminology Criteria for Adverse Events grade or Modified Total Neuropathy Score-reduced, although use of pain medications during chemotherapy might cause worsening of CIPN due to underestimation of subjective symptoms. QOL score based on the EuroQol five-dimensional descriptive system did not worsen during the 12 weeks. Thirty-one percent of patients experienced adverse drug reactions, and the most common event was somnolence (13.5%). Serious adverse events and death occurred in 3 patients and 1 patient, respectively; however, they were unrelated to mirogabalin treatment.

Conclusions: Intervention with mirogabalin during chemotherapy may be effective and safe for cancer patients with moderate to severe CIPN. It can contribute to completion of chemotherapy without worsening of CIPN.

Trial registration: Japan Registry of Clinical Trials (jRCTs031210101, registered 20/5/2021).

Keywords: Analgesia; Cancer; Chemotherapy; Chemotherapy-induced peripheral neuropathy; Mirogabalin; Neurotoxicity; Oxaliplatin; Pain; Taxane.

Fig. 1

Design of the MiroCIP study, which comprised a registrational study and an interventional study. Same-type cancer patients with chemotherapy-induced peripheral neuropathy (CIPN) and receiving oxaliplatin or taxanes outside the registration study part did not participate in the 1-year follow-up registration part of the MiroCIP study. CTCAE, Common Terminology Criteria for Adverse Events; NSCL, non-small-cell lung

Fig. 2

Patient disposition. The per protocol set (PPS) comprised 30 patients, after exclusion of 22 patients from the full analysis set (FAS) for violations of protocol (study drug not administered in compliance with the Japanese package insert of mirogabalin, such as not at twice-daily dosage and not at an effective dosage, n = 20; other violations of eligibility criteria or protocol, n = 2). A total of 40 patients in the FAS and 24 patients in the PPS completed the study; most withdrawals were at the patients’ request

Fig. 3

Pain (including tingling) assessed by numeric rating scale score over 12 weeks of mirogabalin treatment: in the total (full analysis set) (A) and in subgroups with baseline NRS score ≥ 6 (B) or < 6 (C). Data are presented as mean ± SD [95% CI]. The p values, determined by paired t-test, are vs baseline. CI, confidence interval; LOCF, last observation carried forward; NRS, numeric rating scale; SD, standard deviation

Fig. 4

Numbers of patients with change in grade of chemotherapy-induced peripheral neuropathy according to the Common Terminology Criteria for Adverse Events over 12 weeks (full analysis set). Data are presented as percentage of patients. CIPN, chemotherapy-induced peripheral neuropathy