Choice of optimal therapeutic sequence in treatment of patients with progressive / metastatic squamous cell cancer of the head and neck in the light of TPEx study results

Abstract

KEYNOTE-048 study results became basis for changing standard of care in the 1st line treatment of patients with recurrent / metastatic squamous cell cancer of the head and neck (SCCHN). However, there were no significant improvement in the progression free survival for patients receiving pemrolizumab as a monotherapy or in combination with chemotherapy in both group of patients, with PD-L expression (CPS >1) and without it (CPS <1). The latter lead to reassess existing treatment options for patients with progressive recurrent / metastatic SCCHN.TPExtreme study started in 2014 as an open multicenter randomized II phase trial to assess efficacy of a new chemotherapy regimen for the treatment of inoperable recurrent / metastatic SCCHN. Patients in the experimental arm received TPEx regimen: docetaxel 75 mg / m2, cysplatimun 75 mg / m2 and cetuximab 400 mg / m2 on the 1st day (further 250 mg / m2 weekly). Four cycles of TPEx were planned totally with further cetuximab maintenance every 2 week (500 mg / m2) until progression or unfit toxicity. Control arm received EXTREME regimen. Therapeutical effect assessed every 8 weeks. 541 patients were enrolled in study totally (271 patients TPEx arm and 270 patients ETREME arm). Median follow-up were 34.4 months in the TPEx arm and 30.2 months in the ETREME arm, overall survival 14.5 months (95 % confidence interval (CI) 12.5–15.7) and 13.4 months (95 % CI 12.2–15.4) respectively (hazard ratio (HR) 0.89, 95 % CI 0.74–1.08; p = 0,23). Progression-free survival didn’t differ significantly in both groups (HR 0.9, 95 % CI 0.75–1.07). There was no significant difference in objective response rate in both treatment groups. TPEx regimen had favorable safety profile. Quality of life was better in experimental arm also. Authors made conclusion that TPEx regimen could provide an alternative to standard of care with the EXTREME regimen in the first-line treatment of patients with recurrent or metastatic SCCHN, especially for those who might not be good candidates for up-front pembrolizumab treatment. According to KEYNOTE-048 study results, the rate of progression was much higher in patients who received pembrolizumab as a monotherapy (total population) compared to patients received EXTREME (41 % vs 12 %). As a result, the latter led to worsening of progression-free survival in pembrolizumab arm. Pembrolizumab as a monotherapy gives positive effect only in patients with certain level of PD-L expression (CPS >20) in total population. Post-hoc analysis of TPExtreme study demonstrated the most benefit results until now for patients who received consequently cetuximab contained chemotherapy regimens as a first line followed by immunotherapy for the second line in this patients group (overall survival 19.4 months for EXTREME arm and 21.9 months for TPEx arm).Thus TPExtreme study results demonstrates opportunity for better disease control in patients receiving cetuximab in first line and immunotherapy as second line treatment in total population for patients with recurrent / metastatic SCCHN.