Immune Checkpoint Inhibitors: The New Breakout Stars in Cancer Treatm | Page 4

Successes with ipilimumab (CTLA-4 inhibitor), pembrolizumab (PD-1 inhibitor), and nivolumab (PD-1 inhibitor) have led to their approval by the FDA for specific cancers (Table 1). Ipilimumab resulted in a 25% reduction in the relative risk of melanoma recurrence, compared with placebo.4 Tumor regression was experienced following treatment with pembrolizumab by ~24% of patients with unresectable or metastatic BRAF V600 mutation-positive melanoma experiencing progression after ipilimumab treatment.5,6 In a similar MARCH 2011 Ipilimumab (Yervoy®), a CTLA-4 checkpoint inhibitor, was approved by FDA for treatment of refractory or advanced metastatic melanoma SEPTEMBER 2014 Pembrolizumab (Keytruda®), a PD-1 checkpoint inhibitor, granted accelerated approval for treatment of metastatic or unresectable melanoma that did not respond to other treatments DECEMBER 2014 Nivolumab (Opdivo®), a PD-1 checkpoint inhibitor, was approved for treatment of metastatic or unresectable melanoma OCTOBER 2015 Nivolumab (Opdivo®) approved use expanded for treatment of advanced (metastatic) squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy OCTOBER 2015 Pembrolizumab (Keytruda®) granted accelerated approval for treatment of advanced, unresponsive, PD-L1-positive NSCLC OCTOBER 2015 Ipilimumab (Yervoy®) approved as adjuvant therapy with stage III melanoma, to reduce risk of postoperative recurrence NOVEMBER 2015 Nivolumab (Opdivo®) approved use expanded for previously treated metastatic renal cell carcinoma DECEMBER 2015 Pembrolizumab (Keytruda®) approved use expanded to first-line treatment of metastatic or unresectable melanoma Table 1. History of FDA approval of immune checkpoint inhibitors 4 patient group, nivolumab resulted in an objective response rate (ORR) at 6 months of 32%, overall survival of 72.9%, and 5.1-month progression free survival.7,8 Similar durable responses have also been demonstrated in non-small cell lung cancer (NSCLC) and renal cell carcinoma.8 The FDA has also approved the combination of nivolumab and ipilimumab for patients with BRAF wild-type melanoma, who have little to gain from the use of BRAF inhibitors like Zelboraf® (vemurafenib).