Jedd D. Wolchok, MD, PhD
Three years ago, Jedd D. Wolchok, MD, PhD, sat in the lobby of a Chicago hotel at midnight during the ASCO annual meeting with several of his colleagues and sketched out on a napkin a “dream trial” that would simultaneously seek answers to key questions about immune checkpoint therapies just then moving toward center stage in oncology drug development.
This year, Wolchok was back at the 2015 ASCO Annual Meeting with the results from that study—a three-arm trial that compared the PD-1 inhibitor nivolumab (Opdivo) as monotherapy and in combination with the anti-CTLA-4 antibody ipilimumab (Yervoy) versus ipilimumab alone in patients with advanced melanoma.1
The fact that emerging agents employing novel therapeutic strategies could vault so quickly from promising concepts to phase III data involving 945 patients treated at 137 sites in the United States and approximately 12 other countries seems to amaze even Wolchok.
“It’s a very strong indication of how the field is accelerating and I think it demonstrates a very, very firm commitment on the part of investigators and the sponsor as well to find the best treatments as quickly as possible,” he said in an interview at this year’s conference. “This was a truly outstanding accomplishment.”
Indeed, the CheckMate-067 trial on which Wolchok reported emerged as one of the most significant pieces of research presented at ASCO this year—and not simply in terms of efficacy data. The trial findings are part of a growing body of evidence about how best to administer checkpoint-modulating therapies to patients with melanoma and other tumor types in which the therapies likely will be increasingly employed.
Experts say agents that inhibit PD-1/PD-L1 activity are poised to become a backbone of anticancer therapy as important as chemotherapy and, in some malignancies, may someday be a replacement for it.
For clinicians, a central message from 2015 ASCO is that a framework for managing immune- related adverse (iAEs) in patients who receive these immune checkpoint agents is taking shape.
“This is something we’re going to all need to learn how to do and we’re going to all need to embrace because it’s really not just for melanoma patients and not just for ipilimumab anymore,” said Michael A. Postow, MD, a colleague of Wolchok’s at Memorial Sloan Kettering Cancer Center in New York City. “These drugs will likely be FDA approved in many different indications and, even though the side effects are different and the use of the agents may be a little bit different, it’s something that everyone’s going to need to be familiar with.”The PD-1 Landscape
As research unfolds, inhibiting PD-1/PD-L1 activity as an anticancer strategy continues to expand into solid tumor types previously considered unlikely candidates for such an approach. That was among the themes of 2015 ASCO, according to Lynn M. Schuchter, MD, FASCO, a melanoma specialist who served as an ASCO expert commentator at the meeting.
“There were results presented in using PD1 antibody in lung cancer, in head and neck cancer, and in liver cancer, with encouraging results,” Schuchter, chief of Hematology Oncology at Penn Medicine in Philadelphia, said in an interview. “I would say that one theme was the surprise that there is going to be broader applicability of the PD1 antibodies and immunotherapy in more cancers than we had anticipated.”
The Society for Immunotherapy of Cancer (SITC) concentrated on nivolumab and the PD-1 inhibitor pembrolizumab (Keytruda) in developing its list of immunotherapy highlights from this year’s conference (Table 1)
. The list illustrates the list of tumor types in which PD-1 inhibitors are under study as well as the search for biomarkers that might help define the most appropriate patient population for the drugs.
Table 1. Expert Picks on Immunotherapy at ASCO (CLICK TO ENLARGE)
CRC indicates colorectal cancer; DCR, disease control rate; HCC, hepatocellular carcinoma; KLH, keyhole limpet hemocyanin; MMR, mismatch repair; mOS, median overall survival; mPFS, median progression-free survival; NR, not reached; NSCLC, non–small cell lung cancer; ORR, objective response rate; OS, overall survival; PD-L1, programmed death ligand-1; PFS, progression-free survival; RCC, renal cell carcinoma.