Julie M. Vose, MD, MBA, FASCO
ASCO has named immunotherapy, targeting agents that block PD-1/PD-L1 immune checkpoint across a vast array of tumor types, as its “Cancer Advance of the Year.”
The announcement was made as part of ASCO’s release today of its annual update on oncology treatment advances: Clinical Cancer Advances 2016: ASCO's Annual Report on Progress Against Cancer. The report, which explores key advances across cancer care, from prevention, to treatment, to survivorship, was published in the Journal of Clinical Oncology
"No recent cancer advance has been more transformative than immunotherapy. These new therapies are not only transforming patient lives, they are also opening intriguing avenues for further research," said ASCO president Julie M. Vose, MD, MBA, FASCO. "Advances like these require bold ideas, dedication and investment in research. If we are to conquer cancer, we need to invest more as a nation to support a strong biomedical research enterprise."
The report states that PD-1/PD-L1 agents were approved by the FDA in 2015 to treat the most common forms of advanced melanoma, lung cancer and renal cell carcinoma which are otherwise resistant to existing therapies.
In melanoma, 2015 already began with three approvals of checkpoint inhibitors: ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda).
By the end of the year, FDA had expanded the approval for single-agent nivolumab to include the frontline treatment of patients with BRAF
wild-type advanced melanoma.
Most recently, in January 2016, the FDA expanded its frontline approval of nivolumab again, this time as a single agent and in combination with ipilimumab to include BRAF
The expansion is based off of phase III data from the three-arm CheckMate-067 study, in which the combination of nivolumab and ipilimumab reduced the risk of progression by 58% compared with ipilimumab alone in patients with advanced melanoma. Single-agent nivolumab reduced the risk of progression by 43% versus ipilimumab. Outcomes were similar regardless of BRAF
Pembrolizumab also had an expanded frontline approval as a single agent to include the frontline treatment of patients with advanced melanoma regardless of BRAF
status, based on improvements in progression-free and overall survival (OS) compared with ipilimumab in the phase III KEYNOTE-006 trial. The PD-1 inhibitor reduced the risk of disease progression by >40% and the risk of death by >30%, according to the study.
The label for pembrolizumab was also updated to include the treatment of patients with ipilimumab-refractory melanoma, based on a greater than 43% reduction in the risk of death versus chemotherapy in the phase II KEYNOTE-002 trial.
In October 2015, the FDA expanded ipilimumab’s indication to include adjuvant treatment of patients with stage III disease with pathologic involvement in regional lymph nodes >1 mm who have undergone complete resection including total lymphadenectomy.
PD-1/PD-L1 agents aside, the FDA approved the first-in-class oncolytic immunotherapy talimogene laherparepvec (T-VEC) in October 2015 as a local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. The approval was based on findings from the phase III OPTiM study, in which a 4.4-month extension in OS compared with GM-CSF was demonstrated.
In the field of squamous non–small cell lung cancer (NSCLC), nivolumab was approved by the FDA as a therapy for patients whose disease progresses after platinum-based doublet chemotherapy in March 2015. By October that year, the approval was expanded to include patients with nonsquamous NSCLC or EGFR
- or ALK
-targeted agents in patients harboring those mutations.
The approval is based on data from the phase III CheckMate-057 trial, in which second-line nivolumab reduced the risk of death by 27% versus docetaxel in patients with nonsquamous NSCLC, including a 60% risk reduction among patients with the highest levels of PD-L1 expression.
In September 2015, pembrolizumab was given accelerated approval as a treatment for patients with advanced, PD-L1 positive NSCLC who had received prior therapies.
The approval was based on data from the phase I KEYNOTE-001 trial, in which the overall response rate (ORR) with the drug was 41% among a subgroup of 61 patients with pretreated PD-L1–positive advanced NSCLC as determined by the 22C3 pharmDx diagnostic test.
Atezolizumab, another PD-1 blockade, was granted a breakthrough therapy designation in February 2015 for the treatment of patients with PD-L1–positive NSCLC that progresses after platinum-based chemotherapy.
In the phase II BIRCH trial, more than 61% of responses were ongoing after a minimum follow-up of 6 months in patients with stage IIIB/IV or recurrent NSCLC who received atezolizumab.