Nivolumab Survival Benefit Continues in Squamous Cell NSCLC

Roxanne Nelson

September 09, 2015

DENVER — The checkpoint inhibitor nivolumab (Opdivo, Bristol-Myers Squibb) has continued to outshine the chemotherapy docetaxel in lung cancer, according to updated results of a phase 3 trial.

Patients with advanced squamous cell non-small cell lung cancer (NSCLC) who received nivolumab had an 18-month overall survival rate that was more than double that of patients on docetaxel: 28% vs 13%.

The median overall survival was 9.2 months and 6.0 months, respectively, with a hazard ratio favoring nivolumab (HR, 0.62; P = .0004).

New updated findings from the CheckMate 017 trial, which included 272 patients, showed that nivolumab reduced the risk for death by 32% as compared with docetaxel.

"With longer follow-up, nivolumab continues to demonstrate benefit versus docetaxel in previously treated patients with advanced squamous cell NSCLC," said lead author Karen Reckamp, MD, from the City of Hope Comprehensive Cancer Center in Duarte, California, who presented the findings here at the 16th World Conference on Lung Cancer.

Progression-free survival at 18 months was also significantly better with nivolumab, at 17%, compared with 2.7% for docetaxel. The median progression-free survival was 3.5 months and 2.8 months (HR, 0.63; P = .0008).

Nivolumab is a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, and has already demonstrated a survival benefit and manageable safety compared with docetaxel in patients with advanced squamous cell NSCLC.

Earlier survival data from this same study showed 42% of patients treated with nivolumab still alive at one year, compared with 24% of those treated with docetaxel.

Nivolumab reduced the risk for death by 41%, as compared with docetaxel, in this population at 12 months follow-up (HR, 0.59; P = .00025). These earlier data were presented in June at the annual meeting of the American Society of Clinical Oncology (ASCO).

In addition, results of another study (CheckMate 057), also presented at ASCO and reported by Medscape Medical News at that time, found that nivolumab extended median overall survival by 3 months compared with docetaxel (12.2 vs 9.4 months; HR, 0.73; P = .00155), in patients with nonsquamous NSCLC.

"Unprecedented" and "practice-changing," was how the findings from the CheckMate 057 were described by Roy S. Herbst, MD, PhD, from Yale Comprehensive Cancer Center in New Haven, Connecticut, who acted as discussant for the paper.

"This is a positive trial in patients with refractory, nonsquamous advanced NSCLC, the number 1 cause of cancer deaths worldwide," he said at the time of the presentation.

Result Across Subgroups

In this study, 272 patients with squamous NSCLC were randomized to receive nivolumab at 3 mg/kg every 2 weeks (n = 135) or docetaxel at 75 mg/m2 every 3 weeks (n = 137). The primary endpoint of the trial was overall survival and secondary endpoints included objective response rates, progression-free survival, safety, and outcomes by PD-L1 expression.

The overall response rate favored nivolumab (20% vs 9%; P = .0083). A total of 28 patients were treated with nivolumab beyond their initial disease progression, and of this group, nine demonstrated a nonconventional pattern of benefit (ie, reduction in target lesions with simultaneous appearance of new lesions, initial progression followed by tumor reduction, or no further progression for ≥ 2 tumor assessments).

Dr Reckamp also pointed out that even across prespecified cut-points (1%, 5%, and 10%), PD-L1 expression was neither prognostic nor predictive of benefit. "Nivolumab benefit was independent of PD-L1 expression," she said.

Across most predefined patient subgroups, including prior chemotherapy type, region, age, Eastern Cooperative Oncology Group (ECOG) performance status, time from completion of last treatment regimen to randomizations, brain metastases, and smoking status, overall survival favored treatment with nivolumab.

Adverse events of any grade were observed in 59% of patients on nivolumab and 87% of those on docetaxel. Grade 3 or greater events occurred in 8% of patients on nivolumab compared with 58% of those who received docetaxel.

"The safety profile of nivolumab continues to be favorable versus docetaxel and is consistent with prior studies," she said.

Similar Results in Second Study

Strong survival results were also observed in a second study that was presented at this meeting. The CheckMate 063 trial, a smaller single-arm phase 2 trial (n = 117 patients), reported a similar 18-month overall survival rate of 27% in patients with advanced squamous NSCLC.

The median overall survival was 8.1 months (95% confidence interval, 6.1 - 10.9), and 4 of 22 patients treated beyond progressive disease also demonstrated a nonconventional pattern of benefit, similar to that in the CheckMate 017 study. Objective responses were observed across patient subgroups and regardless of PD-L1 expression.

"One of the Best Options"

In a discussion of the papers, Solange Peters, MD, PhD, from the Lausanne University Hospital, Switzerland, noted that the data presented were strong and encouraging.

However, she pointed out that performance status is a limiting factor in second-line treatment for patients with squamous cell NSCLC. All patients in both CheckMate studies had an ECOG status of 0 or 1.

"In the last 15 years there have been a number of randomized phase III trials challenging docetaxel as the standard of care," she said. "Some have been positive."

The results of these studies showed that in unselected patients with squamous cell NSCLC, there was overall survival with afatinib at 7.9 months, erlotinib at 6.8 months, docetaxel alone at 6.3 months, and docetaxel and ramucirumab at 9.5 months.

"I can conclude two things," she said. "One is that nivolumab represents one of the best options you have for second line treatment. Second is that unselected squamous cell cancer of the lung remains a disease characterized by a high unmet medical need."

But that aside, nivolumab showed good survival and has a much more favorable toxicity profile as compared to other agents, Dr Peters said. To date, as real-life studies show, "the elderly, PS2, pretreated patients, regardless of histology, can benefit from nivolumab, and with a similar safety profile."

The study was sponsored by Bristol-Myers Squibb.

Dr Reckamp has received research funding from Bristol-Myers Squibb. Dr Peters reports relationships with several companies, including Bristol-Myers Squibb.

16th World Conference on Lung Cancer (WCLC). Abstract 02.01. Presented September 8, 2015.

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