WASHINGTON – according to Steven F. Powell, MD.
Sharon Worcester/MDedge News
Dr. Steven Powell
Of 34 patients with a mean age of 59 years and stage III-IVb disease enrolled as part of an expansion cohort following a prior study demonstrating the safety of the regimen, 85% had a complete response (CR) at a median follow-up of 21 months based on imaging or salvage surgery, and an additional 2 patients had no clinical evidence of disease, Dr. Powell reported in a late-breaking oral abstract session at the annual meeting of the Society for Immunotherapy of Cancer.
About 80% of the patients had intermediate-risk disease, which is “higher risk than your standard HPV-related cancers,” said Dr. Powell of Sanford Cancer Center, Sioux Falls, S.D.
“On posttreatment imaging ... we showed a 62% complete response rate based on [RECIST 1.1 CT criteria], with 11 patients having a partial response and 2 felt to have a partial response based on CT imaging. Looking at Hopkins criteria [for PET scans] alone – 78% of our patients had a complete response,” he said.
Of the patients with a partial response based on either criteria, 11 were negative for disease on PET and 1 that was positive based on Hopkins criteria underwent neck dissection and had only inflammatory tissue; these 12 patients were also considered to have had a CR.
Additionally, of the two patients with progressive disease, one had a positive PET scan, but all biopsies were negative for ongoing disease, thus that patient was also considered to have a CR, for the overall CR rate of 85%, Dr. Powell said.
Two of the four other patients with a partial response were found at surgery to have “nothing to biopsy or resect,” so it was felt that they had a complete response clinically, and the remaining two had partial responses locoregionally and had residual disease, including residual disease at the primary site in one patient, and nodal disease in one patient.
It is important to consider the challenges of PET imaging in this study, he noted, explaining that in one patient with progressive disease, a posttreatment PET appeared to show bone and dermal metastases, but biopsies of all the areas showed that those were granulomatous disease – most likely sarcoidosis that was not present prior to the treatment.
“This ended up resolving over a year and the PET scan became negative, so I think this highlights that as we move into the curative intent setting we need to be very careful that with PET scanning we need to confirm with biopsy [in patients treated with immuno-oncology] therapies,” Dr. Powell said.
As for survival, the early data are “very encouraging,” with only one patient progressing to date (progression-free survival, 97.1%), but he cautioned that follow-up is “still only 23 months.”
The patient who progressed developed distant metastases and died from their disease, he said.
Treatment in this study included 40 mg/m2 of cisplatin weekly (six planned doses), 200 mg of pembrolizumab every 3 weeks (eight planned doses) and radiation therapy at 2 Gy once daily for 35 fractions (total of 70 Gy). The primary efficacy endpoint was complete response at 100 days after completion of chemoradiotherapy (CRT).
“Looking at safety ... we did not see any new safety signals. We had two dose discontinuations due to immune-related adverse events, which resolved on their own without therapy. Two patients stopped early due to protocol reasons,” Dr. Powell said, noting that the discontinuation rate was comparable with that seen in pembrolizumab monotherapy studies.
Standard therapy compliance was also good, with the chemotherapy goal dose reached in 88% of patients. The CRT dose was reached in all patients with no major delays in treatment.
“So adding CRT did not impact the safety of giving standard therapy,” he said.
Enrollment in this ongoing study was completed as of August, and data for the HPV-negative cohort should be available sometime in 2019. Several correlative research projects are also underway, he said.
The findings thus far show that pembrolizumab can be safely given with CRT in both HPV-positive and HPV-negative disease, with “encouraging response and progression-free survival in predominantly higher-risk patients,” Dr. Powell said.
“It is important to know that PET may pose challenges as we move into big phase 3, randomized trials, and I would strongly recommend biopsy to confirm PET findings,” he said, adding that it will be “interesting to see how this pans out in high-risk disease.
“I’m hopeful that our correlative research will help guide how we time therapy and how we move ahead in this field,” he said.
The Merck Investigator Studies Program provided grant support for this study. Dr. Powell has received research funding (to his institution) from Bristol-Myers Squibb, Genentech, Incyte, Merck, Novartis, and Pfizer.