While the use of nivolumab (Opdivo) plus ipilimumab (Yervoy) shows promise for a subgroup of patients with metastatic colorectal cancer (mCRC), 32% still experienced a treatment-related adverse effect.
While the use of nivolumab (Opdivo) plus ipilimumab (Yervoy) shows promise for a subgroup of patients with metastatic colorectal cancer (mCRC), 32% still experienced a treatment-related adverse effect (TRAE), according to study results presented at the Oncology Nursing Society's 43rd Annual Congress.
In August 2017, the FDA granted accelerated approval to the combination regimen to treat patients with DNA mismatch repair-deficient and/or microsatellite instability-high (dMMR/MSI-H) mCRC that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotec.
In the ongoing, multi-cohort, phase 2 CheckMate-142 study—designed to evaluate the efficacy and safety of nivolumab-based therapies in mCRC—the combination use of nivolumab plus ipilimumab demonstrated promising results, including high objective response rates, durable clinical benefits, encouraging survival and a manageable safety profile, explained Edith Brutcher BSN, MSN, ANP-BC, AOCNP, Emory Winship Cancer Institute.
“The main thing for me is that the concern should be knowing the difference between AEs from immunotherapy and from chemotherapy,” she said in an interview with Oncology Nursing News®. “With triaging and being the nurses taking care of the patients, identifying the different between the symptoms and their management is important.”
For example, AEs with checkpoint inhibition often affect the dermatologic, gastrointestinal (GI), pulmonary, renal, endocrine, and hepatic systems in patients.
“I try to separate the concept of chemotherapy destroying cells as a pain, so it is broad spectrum; and immunotherapy is more focused, but it can focus in on organs,” Brutcher said. “Nurses need to help identify symptoms and teach patients.”
In the trial, 119 patients received 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for four doses, followed by the nivolumab regimen every 2 weeks.
Select TRAEs were managed using protocol-specified algorithms. For example, immune modulatory medications, including corticosteroid treatment and immunosuppressive agents, were used to manage select TRAEs in 22%—56% of patients based on protocol-specific algorithms for organ-specific AEs.
The majority of patients (68%) were aged <65 years, and most (76%) received ≥2 prior lines of systemic therapy, while 86% of patients received all 4 doses of the combination regimen.
During a median follow-up of 13.4 months (range, 9—25 months), 73% of patients reported a TRAE, including 32% who experienced grade 3/4. The most common TRAEs included diarrhea (22%), fatigue (18%), and pruritus (17%). Thirteen percent of patients discontinued treatment due to any-grade TRAEs, most commonly because of autoimmune hepatitis (2%), and acute kidney injury (2%), and 10% because of grade 3/4 TRAEs.
The most common select TRAEs of any grade included skin (29%), endocrine (25%), gastrointestinal (23%), and hepatic (19%) AEs. Most select TRAEs were grade 1 to 2; however, the most common grade 3/4 TRAEs were increased aspartate transaminase (AST; 8%) and alanine transaminase (ALT; 7%) levels. Most select TRAEs of any grade occurred early, with median time to onset in the first 12 weeks of therapy.
Management with protocol-specific algorithms resulted in resolution of nonendocrine select TRAEs in the majority of patients, which included gastrointestinal (96%), hepatic (74%), pulmonary (83%), renal (83%), and skin (71%) AEs; while endocrine select TRAEs were resolved in 40% of patients. The median time to select TRAE resolution ranged from 1.5 to 9 weeks, and median time to resolution for endocrine select TRAEs was not reached.
The majority of patients treated with immune modulatory medications had resolution of their select TRAEs, including all pulmonary effects.
Dose delays caused by select TRAEs occurred in 29 patients (24%); however, combination use of nivolumab plus ipilimumab was resumed in 25 of those patients. Fourteen patients did experience additional select TRAEs after resuming therapy with the regimen.
“The favorable benefit-risk profile of the nivolumab plus ipilimumab combination provides a new treatment option for patients with previously treated dMMR/MSI-H mCRC,” added Brutcher. “Patients get so much information at once and it is such a whirlwind, it is important for nurses to just pull back to the very basics, and say, ‘Remember, this shouldn’t ruin your life. And if in doubt (about an adverse effect), call.’”