Adjuvant nivolumab plus normal chemoradiotherapy ‘great’ for locoregional HNSCC
Key takeaways:
- The addition of nivolumab to plain chemoradiotherapy considerably improved DFS for locoregional HNSCC.
- The proper sequence of immunotherapy might differ relying on the affected person.
CHICAGO — Including adjuvant nivolumab to plain chemoradiotherapy considerably improved DFS for sure sufferers with regionally superior head and neck squamous cell carcinoma, in response to outcomes of a randomized part 3 trial.
The findings, offered at ASCO Annual Assembly, confirmed sufferers with resected, regionally superior HNSCC who obtained nivolumab (Opdivo, Bristol Myers Squibb) had a 24% decrease threat for recurrence or loss of life in contrast with those that didn’t.
Knowledge derived from Bourhis J, et al. Summary LBA2. Offered at: ASCO Annual Assembly; Might 30-June 3, 2024; Chicago.
“[This regimen] might be proposed as a brand new normal therapy, [a first for this patient population] in 2 a long time,” lead creator Jean Bourhis, MD, PhD, chair of radiation oncology at Lundin Household Mind Tumour Analysis Centre at Lausanne College Hospital in Switzerland and co-founder and chair of head and neck oncology group GORTEC, mentioned throughout a press briefing.
No change for many years
Cisplatin-radiotherapy has been normal of take care of sufferers with regionally superior HNSCC for greater than 20 years, however between 40% and 45% of sufferers expertise recurrence.
PD1 inhibitors have been normal of take care of sufferers within the recurrent or metastatic setting, however they haven’t confirmed advantages in regionally superior settings.
Bourhis and colleagues investigated whether or not the addition of nivolumab might enhance outcomes for adults with locoregionally superior HNSCC within the worldwide NIVOPOSTOP trial.
Amongst 666 randomly assigned sufferers, 332 obtained nivolumab plus chemoradiotherapy (median age, 59 years, interquartile vary, 53-65; 75% males; 83% stage IVa or IVb) and 334 obtained chemoradiotherapy alone (median age, 59 years; interquartile vary, 53-64; 77% males; 83% stage IVa or IVb).
The investigational arm obtained 240 mg nivolumab, then chemoradiotherapy plus 360 mg nivolumab each 3 weeks for 3 cycles, adopted by 480 mg nivolumab each 4 weeks for six cycles.
DFS served as the first endpoint; OS and security served as secondary endpoints.
Immunotherapy ‘right here’ for HNSCC
At median follow-up of 30.3 months, the nivolumab arm had considerably improved DFS in contrast with the management arm (HR = 0.76; 95% CI, 0.6-0.98).
Sufferers who obtained nivolumab had a 3-year DFS charge of 63.1% in contrast with 52.5% for many who bought normal of care.
The nivolumab arm had considerably fewer locoregional relapses at 3 years (13% vs. 20%; stratified subHR = 0.63; 95% CI, 0.42-0.94).
Researchers plan to launch OS knowledge sooner or later.
Cisplatin-chemoradiotherapy compliance didn’t differ amongst arms.
Members who obtained nivolumab had the next charge of grade 4 hostile occasions (13.1% vs. 5.6% within the first 100 days after cisplatin-radiotherapy; 1.2% vs. 0% as much as 9 months).
Additionally they had a decrease charge of treatment-related deaths (0.6% vs. 0.7%).
“Many of the toxicity was grade 1 and a couple of and many of the toxicity was immediately associated to chemotherapy and radiotherapy,” Bourhis mentioned.
Bourhis famous the nivolumab arm had larger charge of renal toxicities (24% vs. 15%; grade 3 or 4, 11% vs. 5%) and thyroid dysfunction (20% vs. 2%; all grade 1 or 2), however described these outcomes as “anticipated.”
ASCO skilled Glenn J. Hanna, MD, director of the Heart for Most cancers Therapeutic Innovation at Dana-Farber Most cancers Institute, referred to as the outcomes “great.”
Nevertheless, he additionally mentioned knowledge from KEYNOTE-689, offered at American Affiliation for Most cancers Analysis Annual Assembly, which Healio beforehand reported on.
That research confirmed sufferers with superior HNSCC who obtained neoadjuvant and adjuvant pembrolizumab (Keytruda, Merck) along with normal of care had a major enchancment in EFS.
Moreover, Healio beforehand reported that sufferers who obtained neoadjuvant mixture immunotherapy had numerically superior pathologic tumor response charges than those that obtained monotherapy.
Figuring out which sufferers will profit from which regimens is vital.
“What’s the proper sequence of immunotherapy?” Hanna requested.
Which will depend upon tumor traits.
“Largely the sign for enchancment in outcomes within the preoperative research was in distant metastatic illness — that’s very attention-grabbing,” Hanna mentioned. “Maybe giving immunotherapy upfront mitigates micro-metastatic potential, whereas [in this study], possibly it’s a locoregional affect on nivolumab within the adjuvant setting.
“It’s essential to acknowledge that there could also be sufferers who you’re taking to surgical procedure with scientific options you assume are reasonable threat, like a stage II oral most cancers, after which, oops, you discover out they’ve constructive lymph nodes they usually’re a lot larger threat. You didn’t give preoperative remedy and due to this fact we see a task for the adjuvant therapy.”
Each research present immunotherapy is “right here” for these sufferers, however Hanna cautioned in might take years for follow to fully change.
“Our surgeons should not used to utilizing these brokers within the perioperative setting,” Hanna mentioned. “It is going to be a really great haul and carry for us to persuade the final head and neck surgeon specialist that they should pause, give me a name and let me know that they’ve a affected person with stage III/IVa operable [disease]. In the event that they don’t they usually go to surgical procedure, we could also be considering extra in regards to the paradigm Dr. Bourhis confirmed us the place nivolumab is probably not authorized in america.
“It’ll take years, for my part, for our surgeons to return round,” he added. “They’re fantastic, however out on this planet, getting that knowledge to them in order that they perceive, wait a minute, don’t guide the OR case in 2 weeks as a result of it’s handy and the affected person has ache. It’s essential defer so we will use an essential occasion free survival-based remedy to intervene. That is going to be an enormous situation in our head and neck most cancers subject, at the least within the U.S., over the following a number of years.”
Sources/Disclosures
Collapse
Bourhis J, et al. Summary LBA2. Offered at: ASCO Annual Assembly; Might 30-June 3, 2024; Chicago.
Disclosures:
Bristol Myers Squibb and GORTEC funded the research. Bourhis reviews consulting or advisory roles with AstraZeneca, Bristol Myers Squibb, Merck Serono and MSD. Please see the research for all different authors’ related monetary disclosures.
