Neoadjuvant Therapy Defined as Standard of Care
When considered along with evidence from the phase 2 SWOG 1801 study (N Engl J Med. 2023;388:813-8), “NADINA defines neoadjuvant therapy as the new standard of care for macroscopic stage III melanoma “which means that all trials currently ongoing need to be amended from adjuvant comparators to neoadjuvant comparators,” he said.
Dr. Blank called the trial a “new template for other malignancies implementing a neoadjuvant immunotherapy regimen followed by a response-driven adjuvant therapy.
“I think we see at the moment only sandwich designs, and this is more sales driven than patient driven, because what we have seen is that if a patient achieves a really deep response, the patient doesn’t need an adjuvant part,” he said.
Commenting during the press conference, Michael Lowe, MD, said the result “confirms and shows for the first time in a phase 3 study that giving immunotherapy before surgery results in superior outcomes to giving immunotherapy only after surgery.”
Dr. Lowe, associate professor in the Division of Surgical Oncology, at Emory University School of Medicine, Atlanta, added that the study “also confirms that giving two immunotherapy drugs before surgery results in excellent responses.”
However, he cautioned that “we cannot make comparisons to trials in which patients only got one immunotherapy. But this study confirms that consistency that patients who receive ipilimumab and nivolumab have superior responses compared to single-agent immunotherapy.”
He noted that all of the patients in the new study had all of their lymph nodes removed and called for doing that to remain the standard of care in terms of surgical approach.
“With short follow-up, it is too early to tell if some patients may have benefited from that adjuvant therapy. However, NADINA confirms that immunotherapy should be given to all patients with advanced melanoma before surgery, when possible, and establishes dual therapy with nivolumab and ipilimumab, as the standard of care in the appropriate patient,” Dr. Lowe said.
EFS Improvement Exceeds Expectations
In an interview, Rodabe N. Amaria, MD, a medical oncologist and professor at The University of Texas MD Anderson Cancer Center in Houston, agreed with Dr. Lowe’s assessment of the findings.
“For years we have been doing neoadjuvant immunotherapy trials, all with favorable results, but all relatively small, with data that was intriguing, but not necessarily definitive,” she said. “I see the data from the NADINA trial as being definitive and true evidence of the many advantages of neoadjuvant immunotherapy for clinical stage 3 melanoma ... This work builds on the data from the SWOG 1801 trial but also exceeds expectations with the 68% improvement in EFS appreciated with the dual combination immunotherapy regimen compared to adjuvant nivolumab.”
Additionally, the approximately 30% grade 3 or higher immune-mediated toxicity is reasonable and in keeping with known data, and this trial demonstrates clearly that neoadjuvant immunotherapy does not increase the rate of surgical complications, she said.
Dr. Amaria also considered that 59% of patients who achieved a major pathologic response were observed in the neoadjuvant setting to be a key finding.
This indicates thats “over half the patients could be spared additional immunotherapy and risk of further immune-mediated toxicities by having only two doses of neoadjuvant immunotherapy, she said.
The results “demonstrate the superiority of a neoadjuvant combination immunotherapy approach for patients with clinical stage III melanoma,” she added.
The study was funded by Bristol Myers-Squibb and the Australian government.
Dr. Blank disclosed ties with Immagene, Signature Oncology, AstraZeneca, Bristol-Myers Squibb, GenMab, GlaxoSmithKline, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Roche/Genentech, Third Rock Ventures, 4SC, NanoString Technologies, WO 2021/177822 A1, and Freshfields Bruckhaus Deringer. No other experts reported any relevant disclosures.