The U.S. Food and Drug Administration (FDA) has approved a combination of Opdivo (nivolumab) with low-dose Yervoy (ipilimumab) for the initial treatment of people with metastatic non-small cell lung cancer (NSCLC) whose tumors produce the PD-L1 protein.
The approval is for those without alterations in the EGFR or ALK genes, and comes on the heels of promising findings from part 1a of the CheckMate-227 Phase 3 trial (NCT02477826), in which the double immunotherapy combo significantly extended survival and increased duration of response compared to chemotherapy.
“Patients with metastatic lung cancer remain in need of new treatment options that may provide durable responses,” Matthew D. Hellmann, MD, study investigator, said in a press release.
“The results from the CheckMate-227 trial show that a dual immunotherapy approach offers a chance at long-term survival for appropriate patients with metastatic NSCLC,” added Hellmann, who is also a medical oncologist at Memorial Sloan Kettering Cancer Center.
Opdivo and Yervoy — both sold by Bristol-Myers Squibb — are two immune checkpoint inhibitors that target different proteins involved in the processes used by cancer cells to escape the immune system.
While Opdivo targets the PD-1 protein on T-cells — immune cells with the ability to fight tumors — to boost anti-cancer response by preventing interaction with PD-L1 in tumors, Yervoy targets the CTLA-4 protein also on T-cells, causing them to expand and become activated.
CheckMate-227 is evaluating the safety and efficacy of initial treatment with Opdivo-based regimens versus chemotherapy in patients with advanced NSCLC (metastatic or recurrent).
Part 1a included 793 patients and directly compared a combination of Opdivo plus Yervoy to double-chemotherapy in people who produced the PD-L1 factor — defined as more than 1% of tumor cells being positive for this protein, as determined by an FDA-approved test.
Patients were randomly assigned to receive Opdivo at a dose of 3 mg/kg every two weeks, plus 1 mg/kg Yervoy every six weeks, or chemotherapy every three weeks. Chemotherapy for those with squamous cancer included gemcitabine and either cisplatin or carboplatin. For those with non-squamous cancer, it consisted of Alimta (pemetrexed) and cisplatin or carboplatin, with the option of Alimta maintenance.
After a minimum follow-up of nearly 29 months, the immunotherapy approach had significantly extended patients’ lives to 17.1 months, compared to 14.9 months with chemotherapy. With this 21% reduction in the risk of death, part 1a met its primary goal.
But the trial also showed a sustained improvement in survival, with 33% of patients on immunotherapy being alive after three years, compared with 22% of those on chemotherapy. Also at three years, more patients on Opdivo-Yervoy remained cancer progression-free (18%) compared with 4% of patients receiving chemotherapy.
Also, 36% of patients responded to the immunotherapy approach, including 5.8% complete responses (complete cancer disappearance), with responses lasting a median of 23.2 months. For those on chemotherapy, responses were seen in 30% of patients — including 1.8% complete responses — and their median duration was 6.2 months.
Notably, more patients who were responding to treatment (either partially or completely) at six months lived past the three-year mark, but this was particularly evident among those receiving immunotherapy.
Opdivo-Yervoy’s safety profile was consistent with previous studies, and no new safety signals were observed. About 24% of patients stopped their immunotherapy regimen due to side effects, and about half skipped at least one dose due to an adverse reaction.
Results from this trial, “Nivolumab + ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1,” will be presented at the upcoming American Society of Clinical Oncology Annual Meeting, which will be held online.
“Metastatic lung cancer is a complex and challenging disease. Patients impacted by metastatic NSCLC have been closely watching advances in the field of immunotherapy for additional treatment options that have the potential to significantly extend their lives,” said Bonnie J. Addario, co-founder and chair of GO2 Foundation.
“The fact that certain previously untreated patients now have access to a combination immunotherapy that is chemotherapy-free and has shown a continued survival benefit with more than three years of follow up is an important step in the treatment of the disease,” she added.
