By Diagnostics World Staff
June 16, 2017 | Allan Haberman’s new report, Cancer Immunotherapy: Building on Initial Successes to Improve Clinical Outcomes, discusses the major theme of “second wave” immuno-oncology. He builds on a 2014 Insight Pharma Report which focused on the major classes of cancer immunotherapy drugs that were then emerging from academic and corporate research.
“Immuno-oncology agents such as checkpoint inhibitors represent a significant advance in cancer treatment beyond the traditional modalities of chemotherapy, radiation therapy, and surgery,” writes Haberman.
He revisits three checkpoint inhibitors in particular featured in the 2014 report: ipilimumab, approved by the FDA for treatment of advanced melanoma in 2011; pembrolizumab, formerly known as “MK-3475” or “Merck’s Keytruda”, which received FDA approval in 2014 also for the treatment of melanoma; and nivolumab, which had been approved for treatment of unresectable melanoma in Japan in July 2014 and was in preregistration in the US. The FDA granted accelerated approval to nivolumab for treatment of unresectable or metastatic melanoma on December 22, 2014.
The scope of checkpoint inhibitors has grown, both in the range of treatment in the three previously mentioned checkpoint inhibitors, as well as the number of checkpoint inhibitors being introduced in the discussion. The use of the three drugs had grown to include non-small cell lung cancer (NSCLC). An additional checkpoint inhibitor was also approved by the FDA in May 2016 called atezolizumab, which treats urothelial carcinoma, the most common type of bladder cancer.
The use of immunotherapy, and more specifically checkpoint inhibitors, have seen positive traction in the headlines of treatment. Haberman points to the August 2015 diagnosis of former US president Jimmy Carter. He writes that when President Carter was diagnosed with metastatic melanoma, his treatment involved a combination of stereotactic radiation therapy and pembrolizumab. The former president’s December 2015 diagnostic scans revealed no signs of cancer, Haberman reports.
But that’s not to say checkpoint inhibitors are the end-all cancer treatments. It’s not at all clear whether pembrolizumab, radiation, or surgery lead to the former president’s melanoma remission. However, immunotherapy does play an important role in the advancement of cancer treatment. “Around 10 years ago, melanoma patients with brain metastases had life expectancies measured in weeks and months,” Haberman writes. “Now, there are similar patients… who have been alive for years.”
Though the recent success and spotlight on cancer immunotherapy in the medical community has been a pattern for the last few years, these practices have been in effect in some form or other for close to 125 years.
Haberman writes that in 1891, William B Coley, a surgeon at the New York Cancer Hospital, now Memorial Sloan-Kettering Cancer Center, New York, NY, observed that patients who experienced infections after cancer surgery had better outcomes than those patients who did not experience infections.
“[Coley] hypothesized that mobilization of the immune system to fight the infection counteracted the spread or reappearance of cancer as well,” wrote Haberman. From this hypothesis Coley developed what are known as “Coley’s toxins,” preparations of inactivated bacteria. He injected these preparations into cancerous tumors. Over the next 40 years, Coley saw some in significant successes with the treatment, but positive feedback was sporadic and often difficult to reproduce.
Coley’s toxins were largely abandoned due to these incoherent results, but they helped lay the groundwork for the evolution of cancer immunotherapy. A more modern version of Coley’s toxins is bacillus Calmette-Guerin (BCG). Initially manufactured as a vaccine for tuberculosis, BCG began to be used in the 1980s as treatment of recurrent superficial bladder cancer by being infused directly into the bladder. It remains to be the most effective treatment for early, noninvasive bladder cancer.
“Moreover,” Haberman writes, “a few additional immunotherapeutic drugs have reached the market, and companies and researchers have been hard at work developing additional immuno-oncology treatments, some of which appear to be promising.”
