370P - Low-dose nivolumab with induction chemotherapy for inoperable HNSCC in 111 patients: Response rates, survival, and implications for LMICs

Background

Immune checkpoint inhibitors (ICI) have proven efficacy in R/M HNSCC. In LMICs, <5% of patients have access to ICI at approved doses. We assessed the efficacy of low dose ICI in locally advanced/inoperable HNSCC.

Methods

We conducted retrospective analysis of patients with locally advanced/inoperable HNSCC who underwent induction chemotherapy with low dose nivolumab. Eligible doses of nivolumab were <3mg/kg q2w with chemotherapy backbone of TPX or TP+/- OMCT. The principal outcomes were conversion to radical therapy, ORR, PFS and OS.

Results

We included 111 patients, 78.4% males with median age 48. Primary sites- oral cavity(71.2%), hypopharynx(11.7%), oropharynx(9%) and larynx(8.1%) mainly stage IVA/IVB. TPX/TP was used in 95.4%. Nivolumab 20/40/100 mg all 2/3/4 weeks were the doses and intervals. The harmonized median dose of nivolumab was 0.51 mg/kg q2w (median 3 doses). Response assessment was available for 92 of 111 patients- CR in 7 (6.3%), PR in 65(58.6%), SD in 12(10.8%), PD in 8(7.2%). ORR was 78.2% in those assessed. 25(31.6%) oral cavity tumours became resectable following induction, of whom, 8(32%) had pCR. 60% of oropharyngeal, 69% of hypopharynx and 77.8% of larynx primary site underwent radical RT/CRT after induction. Median PFS is 18.6 months. PFS and OS at 1 year were 64.6% and 82.6%. Median PFS not reached in the cohort with pCR/rCR and 18 months in the group without(p 0.03). No recurrence/death observed thus far in those with pCR. At nivolumab doses <0.6mg/kg, median PFS was significantly lower (13 months vs NR; p 0.04). The retrospective design introduces potential confounders. Grade 3/4 AEs were neutropenia (14.4%), CINV (2.7%), anemia(2.7%), mucositis(1.8%) and febrile neutropenia(1%); Any grade hyponatremia(14%), hypothyroidism(5%).

Conclusions

Low-dose ICI with induction chemotherapy demonstrated promising ORR and conversion to radical therapy. Survival, although immature, appears favourable, especially for patients with pCR/rCR. Doses of nivolumab < 0.6mg/kg may compromise survival. Low-dose (1/6th of standard dose) regimens could enhance ICI access in LMICs due to significantly reduced costs and merit investigation in randomised trials to confirm our findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Institutional Review Board (Ethics committee) of the Christian Medical College Vellor.

Funding

Has not received any fundin.

Disclosure

All authors have declared no conflicts of interest.