Among patients with resectable non-small cell lung cancer (NSCLC), presurgical treatment with Opdivo (nivolumab) plus Yervoy (ipilimumab) has displayed potential long-term clinical benefits versus treatment with chemotherapy, researchers have reported.
Results from the exploratory concurrently randomized Opdivo plus Yervoy and chemotherapy arms of the phase 3 CheckMate 816 clinical trial were published in the Journal of Clinical Oncology. In the trial, adult patients with stage 1B to 3A resectable NSCLC received either Opdivo plus Yervoy (113 patients) or chemotherapy (108 patients).
Researchers reported that at a median follow-up of 49.2 months, the median event-free survival (EFS) was 54.8 months with Opdivo plus Yervoy versus 20.9 months with chemotherapy, and three-year EFS rates were 56% and 44%, respectively. Three-year overall survival rates were73% versus 61% and pathologic complete response (pCR) rates were 20.4% versus 4.6% The rates of major pathologic response (MPR) were 28.3% and 14.8%, respectively.
Glossary:
Resectable: removable by surgery.
Event-free survival: the time after primary treatment for a cancer ends that the patient remains free of certain complications or events that the treatment was intended to prevent or delay, according to the National Cancer Institute.
Overall survival: the time that a patient lives, regardless of disease status.
Pathologic complete response: the lack of all signs of cancer in tissue samples removed during surgery or biopsy after treatment, according to the National Cancer Institute.
Major pathologic response: 10% of fewer viable tumor cells remaining after neoadjuvant therapy.
Neoadjuvant: therapy administered before primary treatment such as surgery.
Adjuvant: therapy administered after primary treatment such as surgery.
Hypothyroidism: underactive thyroid gland.
“Overall, these analyses from CheckMate 816 showed that [Opdivo] plus [Yervoy] can potentially improve long-term survival outcomes and result in increased pCR and MPR rates compared with chemotherapy,” Dr. Mark M. Award and his fellow researchers concluded in the sturdy. Awad is a thoracic medical oncologist with Memorial Sloan Kettering Cancer Center in New York City.
However, researchers noted that the EFS curves for Opdivo plus Yervoy and chemotherapy crossed at nine months, an indication that a greater proportion of patients in the former arm experienced disease progression or death from any cause during the first nine months from random assignment.
Discussing the relevance of the study’s findings, Journal of Clinical Oncology associate editor Dr. Thomas E. Stinchcombe wrote in a contextual piece published along with the study: “Despite the activity observed with [Opdivo] and [Yervoy] in this exploratory analysis the higher rate of early event-free survival events preclude its use in routine clinical care. Additional studies are needed to refine the patient population.”
More From CheckMate 816
In the trial, 91% of patients in the Opdivo plus Yervoy and 86% of patients in the chemotherapy arms completed their prespecified neoadjuvant treatment, with adjuvant treatment received by 34% and 32% of patients, respectively. Subsequent anticancer therapy of any kind was administered to 32% and 49% of patients, respectively, with subsequent systemic therapy received by 30% and 41% of patients.
Eighty-three, or 73%, of patients in the Opdivo plus Yervoy arm and 82, or 76% of patients, in the chemotherapy arms underwent definitive surgery, with reasons for surgery cancellation including disease progression (16% versus 8%) and side effects (3% versus 0%).
Researchers reported recurrence rates after definitive surgery to be 23% in the Opdivo plus Yervoy arm and 44% in the chemotherapy arm.
Regarding safety, side effects of any cause reportedly occurred among 87% of patients in the Opdivo plus Yervoy arm and 99% of patients in the chemotherapy arm, with grade 3 (severe) or 4 (life-threatening) treatment-related side effects reported for 14% and 36% of patients, respectively and treatment-related side effects leading to treatment discontinuation for 5% to 7% of patients.
The most common reported immune-mediated side effects of any grade in the Opdivo plus Yervoy arm were hypothyroidism/thyroiditis (9% of patients) and rash (8%), with the most common immune-mediated side effects of grade 3 to 4 being diarrhea/colitis (3%). Researchers noted that no treatment-related deaths were reported in the Opdivo plus Yervoy arm and one treatment-treated death in the chemotherapy arm.
Opdivo, a type of immune therapy known as an immune checkpoint inhibitor, binds to the protein PD-L1 on the surface of some cancer cells, preventing cancer from suppressing a patient’s immune system, according to the National Cancer Institute. Yervoy, a type of monoclonal antibody and immune checkpoint inhibitor, binds to the protein CTLA-4 to help immune cells better kill cancer cells, the National Cancer Institute explained.
Reference:
“Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer” by Dr. Mark. M. Award, et al., Journal of Clinical Oncology.
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