Nivolumab (Opdivo) plus ipilimumab (Yervoy) didn’t considerably enhance total survival (OS) in contrast with 6 cycles of cetuximab (Erbitux) plus cisplatin/carboplatin plus fluorouracil adopted by cetuximab upkeep (EXTREME routine) in sufferers with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), lacking the first finish level of the CheckMate 651 trial (NCT02741570). Nivolumab/ipilimumab did, nonetheless, show a extra tolerable security profile than EXTREME, based on findings printed within the Journal of Medical Oncology.one
Within the all-patient inhabitants (n = 947), the median OS with the immunotherapy mixture (n = 472) and EXTREME (n = 475) was 13.9 months (95% CI, 12.1-15.8) vs 13.5 months (95% CI , 12.6-15.2), respectively. The HR was 0.95 (97.9% CI, 0.80-1.13; P = .4951). The median OS for sufferers with a mixed constructive rating (CPS) of no less than 20 was 17.6 months (95% CI, 13.8-22.0) with nivolumab/ipilimumab (n = 185) vs 17.6 months (95% CI, 12.3-16.0) with EXTREME (n = 178; HR, 0.78; 97.5% CI, 0.59-1.03; P = .0469).one
Amongst these with a CPS rating of no less than 1, the median OS was 15.7 months with the immunotherapy mixture (n = 355) vs 13.2 months with EXTREME (n = 372; HR, 0.82; 95% CI, 0.69-0.97).one
The twin immunotherapy additionally impressed a shorter median progression-free survival (PFS) vs EXTREME amongst all-treated sufferers (3.3 months vs 6.7 months, respectively), within the CPS higher than or equal to twenty inhabitants (5.4 months vs 7.0 months), and within the CPS of no less than 1 inhabitants (4.2 months vs. 6.1 months).one
Of observe, the speed of the grade 3/4 treatment-related adversarial occasions (TRAE) with nivolumab/ipilimumab was 28.2% amongst all-treated sufferers, whereas the speed noticed with EXTREME was 70.7%.one
“First-line nivolumab plus ipilimumab didn’t lead to a statistically important enchancment in OS vs EXTREME in platinum-eligible R/M HNSCC within the all randomly assigned or CPS [of at least] 20 populations,” wrote Robert I. Haddad, MD, of the Dana-Farber Most cancers Institute and co-investigators, within the examine. “Security with nivolumab plus ipilimumab was favorable in contrast with EXTREME.”one
Examine authors defined that HNSCC is widespread worldwide, and plenty of sufferers initially current with superior illness.2 Over 50% of sufferers with domestically superior HNSCC who obtain multimodal approached develop recurrent or metastatic illness inside 3 years of finishing curative-intent therapies. These sufferers go on to face a poor prognosis with excessive ranges of morbidity and deterioration within the high quality of life.3 To that finish, this examine sought to see if a remedy routine of nivolumab/ipilimumab may enhance survival outcomes on this setting.one
The examine included 947 sufferers with R/M HNSCC who have been naïve to systemic therapies. Members have been randomly assigned 1:1 to obtain both nivolumab plus ipilimumab for as much as 2 years or the EXTREME routine. The median age was 61 years (vary, 24-86) within the twin immunotherapy arm and 62 years (vary, 29-86) within the EXTREME arm. Between the two arms, 80.5% and 83.6% have been male, 76.3% and 77.7% have been present or former people who smoke, 39.2% and 37.5% had CPS of no less than 20, and 57.2% and 57.7% had tumor PD-L1 expression of no less than 1%, respectively.one
OS was a twin main finish level within the all-patient and CPS of no less than 20 populations. OS within the PD-L1 CPS of no less than 1 inhabitants, together with PFS, total response charge (ORR), and period of response (DOR) in all randomly assigned and CPS of no less than 20 populations have been secondary finish factors.one
The minimal follow-up was 27.3 months, and the median follow-up was 39.1 months. At database lock, no sufferers remained on remedy on the nivolumab/ipilimumab arm and 40 sufferers (8.5%) had accomplished the total 2 years of remedy. At information cutoff, remedy was ongoing for 1.6% of sufferers within the EXTREME arm.
The median period of remedy was 3.8 months vs 5.0 months with nivolumab/ipilimumab vs EXTREME within the all-patient inhabitants, respectively. A median of 8 doses of nivolumab and three doses of ipilimumab have been administered.
Within the EXTREME arm, 24% of sufferers acquired cisplatin, 54% acquired carboplatin, and 11% acquired each cisplatin and carboplatin throughout remedy. The median dose of cisplatin and carboplatin administered throughout therapies was 4 and 5 doses, respectively. A complete of 52.8% of sufferers acquired cetuximab (Erbitux) upkeep.
Moreover, subsequent systemic remedy was administered to 29.2% and 60.2% of sufferers on the twin immunotherapy and EXTREME regimens, respectively, with 8.5% and 46.3% of sufferers receiving subsequent immunotherapy, most of whom went on to nivolumab. Further therapies included receiving platinum-based chemotherapy (42.2% vs 16.2%, respectively), and cetuximab (27.3% vs 12.8%).
To account for variety of sufferers within the EXTREME arm receiving subsequent immunotherapy was a lot higher than the experimental arm (46% vs 9%). Following this adjustment, the median OS within the all-patient inhabitants was 12.4 months with twin immunotherapy in contrast with 10.8 months with EXTREME (HR, 0.80; 95% CI, 0.68-0.92). Within the CPS of no less than 20 inhabitants the median OS was 14.1 months vs. 11.7 months (HR, 0.71; 95% CI, 0.55-0.99).
The speed of any-grade TRAEs have been 72.2% vs 97.5% with nivolumab/ipilimumab vs EXTREME. The commonest any-grade TRAES with nivolumab plus ipilimumab have been fatigue (18.2%), pruritus (15.0%), and hypothyroidism (14.1%). With EXTREME, the commonest any-grade TRAEs have been nausea (44.7%), rash (38.3%), and anemia (34.9%).
For sufferers who skilled any-grade immune-related adversarial occasions, the commonest have been hypothyroidism/thyroiditis (16.0%), rash (12.6%), and hyperthyroidism (6.8%). Grade 3/4 occasions have been unusual, and most occasions occurred inside the first 5 months of remedy.
“Use of immunotherapy within the remedy of [HNSCC] continues to be evolving, with a continued unmet want for first-line regimens that present sturdy scientific profit with tolerable security,” Gary Okay. Schwartz, MD, a medical oncologist with Colombia College Medical Middle and affiliate editor with the Journal of Medical Oncology, wrote in an evaluation of the findings. “Additional analysis is required to find out the utility of twin immunotherapy as a remedy possibility for [HNSCC] and establish novel biomarkers to foretell profit with immunotherapy.”
- Haddad RI, Harrington Okay, Tahara M, et al. Nivolumab plus ipilimumab versus EXTREME routine as first-line remedy for recurrent/metastatic squamous cell carcinoma of the top and neck: the ultimate outcomes of CheckMate 651. J Clin Oncol. Printed on-line December 6, 2022. doi:10.1200/JCO.22.00332
- Sung H, Ferlay J, Siegel RL, et al. International most cancers statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 international locations. CA Most cancers J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
- Chow LQM. Head and neck most cancers. N Engl J Med. 2020;382(1):60-72. doi:10.1056/NEJMra1715715