Martin Reck, MD, PhD
Ramucirumab (Cyramza) plus docetaxel demonstrated an overall survival (OS) benefit versus placebo plus docetaxel in patients with advanced non–small cell lung cancer (NSCLC) whose disease rapidly progressed on first-line therapy, according to an exploratory, posthoc analysis from the phase III REVEL trial.
Data from the posthoc analysis of the angiogenesis inhibitor were presented at the International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer. Investigators reported that, compared with placebo/docetaxel, ramucirumab/docetaxel was associated with improved median OS at time-to-progression (TTP) of ≤9 weeks (8.28 vs 4.83 months; hazard ratio [HR], 0.69; 95% CI, 0.47-1.01), ≤12 weeks (9.10 vs 5.78 months; HR, 0.74; 95% CI, 0.54-1.00), and ≤18 weeks (8.51 vs 5.95 months; HR, 0.80; 95% CI, 0.63-1.01).
Those findings were similar to previously released median OS data from the intent-to-treat (ITT) population (N = 1253), which also favored the ramucirumab arm (10.51 vs 9.13 months; HR, 0.86; 95% CI, 0.75-0.98). Based on these ITT data, the FDA approved ramucirumab in December 2014 for use in combination with docetaxel for the treatment of patients with metastatic NSCLC with disease progression on or after platinum-based chemotherapy.
“Despite recent advancements, patients with aggressive, rapidly progressing advanced non–small cell lung cancer who progress before or at the time of their first scan—which is typically done between nine and 12 weeks—often have a less favorable response to their second-line therapy,” Martin Reck, MD, PhD, department of thoracic oncology, Lung Clinic Grosshansdorf, said in a press release. “This is a population that has poor prognosis and immediate unmet needs with limited treatment options.”
“This REVEL exploratory analysis demonstrated that efficacy, safety, and quality-of-life outcomes among patients receiving ramucirumab plus docetaxel who have aggressive disease with rapid progression on first-line therapy are consistent with the outcomes of the intent-to-treat population. These results suggest that such patients may derive meaningful benefit from ramucirumab plus docetaxel in the second-line setting,” added Reck.
The global, randomized, double-blind, placebo-controlled REVEL trial evaluated the combination of ramucirumab and docetaxel in patients with metastatic NSCLC whose cancer progressed on or after prior platinum-based chemotherapy for locally advanced or metastatic disease. Patients with nonsquamous (73%) and squamous (26%) forms of NSCLC were included in the study. Data from the ITT population were first presented at the 2014 ASCO Annual Meeting.
In the posthoc analysis of patients with rapid progression on first-line therapy, 11% (n = 133) of patients had TTP ≤9 weeks, 17% (n = 209) had TTP ≤12 weeks, and 28% (n = 354) had TTP ≤18 weeks. Baseline characteristics of each subgroup were balanced between treatment arms.
Beyond the OS benefit, the data also showed a trend favoring the ramucirumab arm for median progression-free survival (PFS) at TTP ≤9 weeks (3.01 vs 1.48 months; HR, 0.69; 95% CI, 0.48-0.98), ≤12 weeks (3.61 vs 1.61 months; HR, 0.73; 95% CI, 0.55-0.97), and ≤18 weeks (3.22 vs 1.61 months; HR, 0.72; 95% CI, 0.58-0.89). These data were consistent with the median PFS benefit for ramucirumab in the ITT population (4.50 vs 3.02 months; HR, 0.78; 95% CI, 0.69-0.87).
Similarly, objective response rate (ORR) was superior the ramucirumab arm at TTP ≤9 weeks (18.3% vs 3.2%), ≤12 weeks (18.9% vs 9.2%), and ≤18 weeks (19.2% vs 10.5%). These results were again consistent with the ORR benefit with ramucirumab in the ITT population (22.9% vs 13.6%).
“We are encouraged by this REVEL subgroup analysis, as patients with this aggressive type of cancer who experience rapid disease progression on first-line therapy urgently need additional treatment options that can help stop or slow the cancer from growing and spreading," Levi Garraway, MD, PhD, senior vice president, global development and medical affairs, Lilly Oncology, said in a press release. “The results of this REVEL analysis add to the growing body of knowledge we have about aggressive lung cancer.”
Safety overview outcomes from patients with TTP on first-line therapy ≤18 weeks are similar to what was observed from patients with TTP on first-line therapy ≤9 weeks and ≤12 weeks, as well as in the ITT population. There were no new safety signals observed in these subpopulations.
Rapidly Progressing Advanced Non-Small Cell Lung Cancer Patients Shown to Benefit in New CYRAMZA® (ramucirumab) Phase 3 Subgroup Analysis. http://bit.ly/2hLKh6P. Eli Lilly and Company. Accessed October 17, 2017.