3667 - Effect of Time-of-Day Nivolumab and Stereotactic Body Radiotherapy in Metastatic Head and Neck Squamous Cell Carcinoma: A Secondary Analysis of a Prospective Randomized Trial

J. Janopaul-Naylor¹, L. A. Boe², Y. Yu¹, E. Sherman³, D. G. Pfister³, N. Y. Lee¹, and S. McBride¹; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Memorial Sloan Kettering Cancer Center, New York, NY, ³Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): Retrospective and prospective evidence suggests a link between the circadian rhythm and efficacy and toxicity of cancer therapies. We aimed to identify if time-of-day influenced outcomes after nivolumab with or without stereotactic body radiotherapy (RT) for metastatic head and neck squamous cell carcinoma (HNSCC). Materials/

Methods: We performed a secondary analysis of a single-center, randomized, phase II trial of nivolumab (3 mg/kg IV every 2 weeks) versus nivolumab (same dose) plus RT (9 Gy x 3) in adults with metastatic HNSCC. We used cutoffs of 11 AM and 4:30 PM based on prior studies of immune-circadian rhythm to define AM and PM treatment. Nivolumab classified by first infusion time (e.g. AM Nivo infusion started before 11 AM), while RT classified by timing of majority of fractions (e.g. PM RT defined by 2 or 3 fractions after 4:30 PM). Outcomes assessed included OS, PFS, and Grade 3 or 4 adverse events.

Results: There were 62 patients randomly assigned to nivolumab (n=30) or nivolumab plus RT (n=32). Patient details by treatment arm and time-of-day therapy in Table. For patients treated with AM nivolumab, PM nivolumab, or not AM or PM nivolumab there was no statistically significant difference in OS (422 days vs 435 days vs 435 days, p>0.9), PFS (175 days vs 58 days vs 67 days, p=0.8), or toxicity (p=0.7). For patients treated with AM RT, PM RT, or not AM or PM RT there was no statistically significant difference in OS (432 days vs 615 days vs 350 days, p=0.9), PFS (78 days vs 111 days vs 63 days, p=0.9), or toxicity (p=0.2). On subset analysis, we saw that patients treated with PM Nivo with RT (n=11) compared to without RT (n=10) had no significantly different median OS (468 days vs 294 days, p=0.8) or PFS (64 days vs 56 days, p>0.9).

Conclusion: On a prospective randomized clinical trial of immunotherapy with or without stereotactic body radiotherapy for HNSCC, we found no significant association between time-of-day infusion or radiotherapy and OS, PFS, or adverse events. Further work may elucidate the optimal patients, tumors, and therapies that are affected by diurnal variation. Abstract 3667 – Table 1

	AM Nivolumab (n=7)	PM Nivolumab (n=21)	Not AM or PM Nivolumab (n=34)	AM RT (n=4)	PM RT (n=13)	Not AM or PM RT (n=15)
Median age (range)	66 (55-74)	63 (42-76)	62 (29-83)	68 (65-69)	63 (35-83)	66 (49-78)
NPX	1 (14%)	3 (14%)	6 (18%)	2 (50%)	2 (15%)	0 (0%)
OPX	4 (57%)	7 (33%)	11 (32%)	1 (25%)	3 (23%)	7 (47%)
Other Primary Site	2 (29%)	11 (52%)	17 (50%)	1 (25%)	8 (62%)	8 (53%)
Median lines prior chemo (range)	1 (0-3)	2 (0-3)	1 (0-3)	2 (0-3)	1 (0-3)	1 (0-3)
No Prior Chemo	1 (14%)	2 (10%)	4 (12%)	1 (25%)	3 (23%)	2 (13%)
PD-L1 Negative	3 (43%)	13 (62%)	20 (59%)	2 (50%)	6 (46%)	10 (67%)
PD-L1 Positive	4 (57%)	7 (33%)	11 (32%)	1 (25%)	6 (46%)	4 (27%)
PD-L1 Not Available	0 (0%)	1 (5%)	3 (9%)	1 (25%)	1 (8%)	1 (7%)