By David Hewitt, Vice President of Medical and Scientific Affairs, inVentiv Health Clinical Division
There are many reasons to be excited by the science being presented at this year’s American Society for Clinical Oncology meeting. The data presented at a special section on Saturday morning opened the door to a future when tumor genetics and biomarkers will change the way we think of about cancer treatment. As a physician working in clinical development, there is also the excitement around intriguing new questions that when answered could lead to life-saving treatments unimaginable just a decade ago.
More than 2,000 people packed into a cavernous conference hall at 8 a.m. on Saturday – demonstrating the high level of shared interest in emerging immunotherapies.
Three presentations in the morning session produced three big takeaways. First, that immune check point inhibitors are continuing to demonstrate potential efficacy in treating some difficult to treat tumor types. Second, that the genetics of the tumor has the potential to rival the primacy of tumor histology in determining treatment. And finally, that investigator led studies comprise some of the most innovative research being done and merit the full support of industry.
I continue to be struck by how fast advances are occurring in immunotherapies and checkpoint inhibitors with a rapidly growing body of data generated by tremendous research activity. Dr. Neil Howard Segal of Memorial Sloan Kettering Cancer Center opened the session on “Immunotherapy for Every Patient: Check Your Enthusiasm” with data showing that in his review of the Cinicaltrials.gov database, 279 of the 6,018 clinical trials going on in cancer were focused on checkpoint inhibitors.
The first study in the session focused on patients with colorectal cancer with or without DNA mismatch mutation repair deficiency, and included a non colorectal MMR deficiency group of multiple tumor types. The study found that MMR deficiency was highly correlated with efficacy and progression-free survival in patients with MMR deficiency associated with colon cancer, as well as other tumor types. The early-phase study indicated that while anti PD-1 may not be effective in 95% of colon cancer patients, for the 4-5% carrying the genetic mutations, the immunotherapy could be miraculous.
This was the first study to use a tumor’s genetics to guide immunotherapy and set the stage for further studies assessing the impact of tumor genetics on the efficacy of drugs used in the treatment of cancer. This holds promise for a personalized medicine approach to the treatment of cancer. The results of this investigator-initiated study have led Merck to do a larger study to confirm these findings (KEYNOTE164).
The second study assessed the anti PD-1 inhibitor Nivolumab in patients with hepatocellular carcinoma. Liver cancer is the second most frequent cause of cancer-related deaths worldwide. The data presented provides early clinical data suggesting that anti PD-1 may be effective in the treatment of liver cancer. Investigators reported a fairly robust response rate in a small cohort and reported interesting results in patients, with chronic Hepatitis B or Hepatitis C, as well as uninfected patients. The study found that 7 out of 8 patients had a response rate lasting 9 months or longer, with greatest response occurring within the first two months of trial.
Nivolumab is currently approved for the treatment of squamous non-small cell lung cancer (NSCLC). Investigators in the third presentation Saturday morning presented data from a Phase III trial comparing Nivolumab to Docetaxel in advanced non-squamous cell (non-SQ) lung cancer. The results look quite good. There was improvement in the overall survival rate and, most interestingly, a robustly better safety profile than Doxcetaxel, the current standard of care of second line therapy.
This study presented evidence that the amount of tumor expression of PDL-1 is predictive of efficacy. Patients with low levels of PDL-1 did not respond as well or live as long as those with higher levels (>1%). However, the data set was incomplete with 20% of patient having had no sample assessed for PDL-1. Confirmation of the importance of PDL-1 levels will need to be the subject of future studies. Nonetheless, the results as they stand are impressive.
Dr. Roy S. Herbst of Yale’s School of Medicine in his discussion of this study found the results so compelling that he endorsed the use of Nivolumab for the treatment of NSCLC, despite the need for further clarification of the utility of PDL-1 expression.
Herbst concluded by suggesting next steps in immunotherapy research should include the testing of combinations of therapies to overcome primary and acquired resistance. This will require a substantial effort on the part of pharmaceutical companies and partnership with the most sophisticated drug development organizations.
Results from just such a study assessing the anti PD-1 inhibitor (Opdivo) in combination with the CTLA-4 inhibitor (Yervoy) to treat melanoma will be presented on Sunday.
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