Lobaplatin Combination Regimen May Minimize Toxicity in HNSCC

Induction chemotherapy combined with concurrent lobaplatin chemoradiotherapy improved safety outcomes without sacrificing efficacy vs a cisplatin-based regimen in patients with head and neck squamous cell carcinoma.

For patients with locally advanced head and neck squamous cell carcinoma (HNSCC), treatment with docetaxel (Docefrez) plus lobaplatin (TL) induction chemotherapy combined with concurrent lobaplatin chemoradiotherapy (CRT) resulted in similar efficacy and reduced toxicity vs docetaxel plus cisplatin plus 5-fluorouracil (TPF) induction chemotherapy combined with concurrent cisplatin CRT, according to early findings from a phase 3 trial (NCT03117257) presented at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.

Investigators found no significant difference with regard to short-term objective response rate (ORR) between the TL and the TPF groups (P = .208) after a median follow-up of 35 months (range, 19-57). Additionally, the 2-year overall survival (OS) rate was 54.3% in the TL group vs 66.7% in the TPF group (P = .342), and the 2-year progression-free survival (PFS) was 61.1% vs 71.4% in each arm, respectively (P = .200).

Investigators also reported that TL demonstrated a better safety profile during induction chemotherapy than the TPF regimen. Grade 1/2 nausea or vomiting occurred in 10% of patients in the TL group vs 51% of those in the TPF group (P <.001), hyperbilirubinemia occurred in 14% vs 36% (P = .023), and hyponatremia occurred in 21% vs. 71% (P <.001). Similarly, the incidence of grade 3/4 absolute neutrophil count reduction was 17% in the TL group and 51% in the TPF group (P = .001). The same pattern emerged during CRT, with investigators reporting an incidence of grade 1/2 creatinine elevation, hyponatremia, and hypokalemia in 2% vs 20% (P = .010), 14% vs. 69% (P <.001), and 19% vs 62% (P <.001) of patients in the TL and TPF groups, respectively. Grade 3/4 thrombocytopenias occurred in 24% of patients in the TL group vs 4% of those in the TPF group (P = .009). Notably, TL maintained the better profile overall.

“For locally advanced [HNSCC, lobaplatin] combined regimen induction chemotherapy followed by [lobaplatin] concurrent CRT may be a new choice for second-line treatment. [The lobaplatin] regimen had obvious advantages in reducing toxic and adverse effects, and the efficacy needs further follow-up verification,” investigators wrote.

The trial enrolled 87 patients with pathologically confirmed, locally advanced HNSCC from August 2016 to October 2019, all of whom adopted the chrono-chemotherapy mode following randomization to the TL and TPF groups. Patients were included if they had no surgery and stage III to IVb; or surgery and stage IVa or IVb disease, stage III disease at either tongue base or hypopharyngeal primary sites, or postoperative naked eye or image residual stage III disease. Other requirements included a Karnofsky score of 70 or more, an expected survival time of 6 months or more, and an endogenous creatinine clearance rate of 55 ml per minute or more.

Meanwhile, patients who had received epidermal growth factor targeted therapy or whose primary tumors had been treated previously with chemotherapy or immunotherapy were excluded from the trial.

These data, although circumscribed by a limited participant population, nonetheless suggest that the lobaplatin regimen could be a promising second-line option for this patient population.

Reference

Zhang M, Wu W, Jin F, et al. A randomized phase III trial observed the feasibility and safety of loplatin combination regimen of sequential loplatin in locally advanced head and neck SCC. Presented at 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting; October 23-26, 2022; San Antonio, TX; abstract 2637. Accessed October 26, 2022.