Comparative analysis of induction chemotherapy followed by chemoradiotherapy and concurrent chemoradiation therapy efficacy in patients with locally advanced head and neck squamous cell cancer

Treatment strategy of advanced unresectable head and neck squamous cell cancer (HNSCC) is limited to induction chemotherapy (ICT) followed by (chemo) radiotherapy (cRT) and concurrent chemoradiotherapy (CCRT). However, the role of ICT remains controversial considering the lack of overall survival benefit.

The aim: to evaluate the role of induction chemotherapy in the treatment of locally advanced HNSCC.

Methods: We performed a retrospective clinical study that included patients (pts) with unresectable stage III–IVa cancer of larynx, oropharynx and hypopharynx.

Results: A total of 176 pts were enrolled, 84 (48 %) received CCRT with cisplatin or carboplatin and 92 (52 %) — ICT followed by cRT. Groups were well balanced by sex, tumor site, T-stage, while in group of ICT there was a significant prevalence of younger pts (p = 0.004) and pts with stage N2–3 (p = 0,03).

The objective response rates (ORR) were 76 % (42 / 55) in CCRT arm (including 53 % (12 / 62) of complete responses) and 72 % (56 / 78) in ICT arm with complete response rate of 15 % (12 / 78). The ORR in ICT arm increased after the completion of CCRT up to 82 % with 53 % (33 / 62) of complete responses. The difference was not statistically significant (p = 0,7).

With a median follow-up duration of 8.7 months median progression-free survival (mPFS) was 7.6 and 9.4 months (Hazard ratio (HR) 0.67, 95 % CI 0.43–1.04); 6month OS was 65.7 % and 92.8 % in CCRT and ICT groups, respectively (HR 0.51, 95 % CI 0.30–0.85, р < 0.01).

Propensity score matching analysis proved the 6month OS in the ICT + cRT group to be significantly longer than in CCRT group — 97.7 % vs 66.8 %, respectively (HR = 0.28, 95 % CI 0.13–0.62, p  < 0.01).

Conclusions: ICT + сRT resulted in improvement of PFS and OS compared to CCRT in pts with locally advanced HNSCC.

1. The state of cancer care for the population of Russia in 2022. Eds.: А.D. Kaprin, V.V. Starinskiy, A.O. Shachzadova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2022.239 p (In Russ.)

2. Posner M.R., Hershock D.M., Blajman C.R., et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357(17):1705–1715. https://doi.org/10.1056/nejmoa070956

3. Vermorken J.B., Remenar E., van Herpen C., et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007;357(17):1695–1704. https://doi.org/10.1056/nejmoa071028

4. Adelstein D.J., Li Y., Adams G.L., et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003;21(1):92–8. https://doi.org/10.1200/JCO.2003.01.008

5. Pignon J.P., Le Maitre A., Maillard E., Bourhis J. Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACHNC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92(1):4–14. https://doi.org/10.1016/j.radonc.2009.04.014

6. Okano S., Homma A., Kiyota N., et al. Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck. Jpn J Clin Oncol 2021;51(2):173–179. https://doi.org/10.1093/jjco/hyaa220

7. Rosenbaum P.R., Rubin D.B., The central role of the propensity score in observational studies for causal effects. Biometrika 1983;70(1):41–55. https://doi.org/10.1093/biomet/70.1.41

8. National Comprehensive Cancer Network (NCCN). Head and Neck Cancer, Version 4.2024. NCCN Clinical Practice Guidelines in Oncology. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf

9. Gregoire V., Lefebvre J.L., Licitra L., Felip E. Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21(5):v184–6. https://doi.org/10.1093/annonc/mdq185

10. Bolotina L.V., Vladimirova L.Yu., Dengina N.V., et al. Head and neck tumors. Zlokachestvennie opuholi = Malignant Tumors 2023;13(3s2–1): 100–119 (In Russ.). https://doi.org/10.18027/2224-5057-2023-13-3s2-1-100-119

11. Mehanna H., Robinson M., Hartley A., et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet 2019;393(10166):51–60. https://doi.org/10.1016/S0140-6736(18)32752-1

12. Schüttrumpf L., Marschner S., Scheu K., et al. Definitive chemoradiotherapy in patients with squamous cell cancers of the head and neck - results from an unselected cohort of the clinical cooperation group “Personalized Radiotherapy in Head and Neck Cancer”. Radiat Oncol 2020;15(1):7. https://doi.org/10.1186/s13014-019-1452-4

13. Haddad R., O’Neill A., Rabinowits G., et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013;14(3):257–64. https://doi.org/10.1016/S1470-2045(13)70011-1

14. Zanoni D.K., Patel S.G., Shah J.P. Changes in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging of Head and Neck Cancer: Rationale and Implications. Curr Oncol Rep 2019;21(6):52. https://doi.org/10.1007/s11912-019-0799-x

15. Lazarev S., Gupta V., Ghiassi-Nejad Z., et al. Premature discontinuation of curative radiation therapy: Insights from head and neck irradiation. Adv Radiat Oncol 2017 Oct 23;3(1):62–69. https://doi.org/10.1016/j.adro.2017.10.006

16. Rocha P.H.P., Reali R.M., Decnop M., et al. Adverse radiation therapy effects in the treatment of head and neck tumors. Radiographics 2022;42(3):806–821. https://doi.org/10.1148/rg.210150

17. Lorch J.H., Goloubeva O., Haddad R.I., et al. Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol 2011;12(2):153–9. https://doi.org/10.1016/S1470-2045(10)70279-5

18. Adelstein D.J., Moon J., Hanna E., et al. Docetaxel, cisplatin, and fluorouracil induction chemotherapy followed by accelerated fractionation/concomitant boost radiation and concurrent cisplatin in patients with advanced squamous cell head and neck cancer: a Southwest Oncology Group phase II trial (S0216). Head Neck 2010;32(2):221–228. https://doi.org/10.1002/hed.21179

19. Chitapanarux I., Lorvidhaya V., Kamnerdsupaphon P., et al. Systemic therapy/RT comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer 2007;43(9):1399–1406. https://doi.org/10.1016/j.ejca.2007.03.022

20. Noronha V., Joshi A., Patil V.M., et al. Once-a-week versus once-every-3-weeks cisplatin systemic therapy/RT for locally advanced head and neck cancer: a phase III randomized noninferiority trial. J Clin Oncol 2018:36(11):1064–1072. https://doi.org/10.1200/JCO.2017.74.9457.