Key takeaways:
- The addition of nivolumab to straightforward chemoradiotherapy considerably improved DFS for locoregional HNSCC.
- The right sequence of immunotherapy might differ relying on the affected person.
CHICAGO — Including adjuvant nivolumab to straightforward chemoradiotherapy considerably improved DFS for sure sufferers with regionally superior head and neck squamous cell carcinoma, based on outcomes of a randomized part 3 trial.
The findings, introduced at ASCO Annual Assembly, confirmed sufferers with resected, regionally superior HNSCC who acquired nivolumab (Opdivo, Bristol Myers Squibb) had a 24% decrease danger for recurrence or demise in contrast with those that didn’t.
Information derived from Bourhis J, et al. Summary LBA2. Offered at: ASCO Annual Assembly; Might 30-June 3, 2024; Chicago.
“[This regimen] may very well be proposed as a brand new customary 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, stated throughout a press briefing.
No change for many years
Cisplatin-radiotherapy has been customary of look after sufferers with regionally superior HNSCC for greater than 20 years, however between 40% and 45% of sufferers expertise recurrence.
PD1 inhibitors have been customary of look after 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 acquired nivolumab plus chemoradiotherapy (median age, 59 years, interquartile vary, 53-65; 75% males; 83% stage IVa or IVb) and 334 acquired chemoradiotherapy alone (median age, 59 years; interquartile vary, 53-64; 77% males; 83% stage IVa or IVb).
The investigational arm acquired 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 acquired nivolumab had a 3-year DFS fee of 63.1% in contrast with 52.5% for many who received customary 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 information sooner or later.
Cisplatin-chemoradiotherapy compliance didn’t differ amongst arms.
Contributors who acquired nivolumab had a better fee 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 fee of treatment-related deaths (0.6% vs. 0.7%).
“Many of the toxicity was grade 1 and a pair of and many of the toxicity was instantly associated to chemotherapy and radiotherapy,” Bourhis stated.
Bourhis famous the nivolumab arm had increased fee 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 knowledgeable Glenn J. Hanna, MD, director of the Heart for Most cancers Therapeutic Innovation at Dana-Farber Most cancers Institute, known as the outcomes “super.”
Nonetheless, he additionally mentioned information from KEYNOTE-689, introduced at American Affiliation for Most cancers Analysis Annual Assembly, which Healio beforehand reported on.
That examine confirmed sufferers with superior HNSCC who acquired neoadjuvant and adjuvant pembrolizumab (Keytruda, Merck) along with customary of care had a major enchancment in EFS.
Moreover, Healio beforehand reported that sufferers who acquired neoadjuvant mixture immunotherapy had numerically superior pathologic tumor response charges than those that acquired monotherapy.
Figuring out which sufferers will profit from which regimens is essential.
“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 examine was in distant metastatic illness — that’s very attention-grabbing,” Hanna stated. “Maybe giving immunotherapy upfront mitigates micro-metastatic potential, whereas [in this study], perhaps it’s a locoregional impression 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 suppose are average danger, like a stage II oral most cancers, after which, oops, you discover out they’ve optimistic lymph nodes and so they’re a lot increased danger. 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 are usually not used to utilizing these brokers within the perioperative setting,” Hanna stated. “It is going to be a really super haul and elevate for us to persuade the overall 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 and so they go to surgical procedure, we could also be pondering extra in regards to the paradigm Dr. Bourhis confirmed us the place nivolumab will not be authorised in the USA.
“It’s going to take years, in my view, for our surgeons to return round,” he added. “They’re fantastic, however out on this planet, getting that information 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 is advisable to defer so we are able to use an essential occasion free survival-based remedy to intervene. That is going to be an enormous challenge in our head and neck most cancers subject, a minimum of within the U.S., over the subsequent 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 examine. Bourhis studies consulting or advisory roles with AstraZeneca, Bristol Myers Squibb, Merck Serono and MSD. Please see the examine for all different authors’ related monetary disclosures.
