Immune to Cancer: The CRI Blog



ASCO19 Day 1 Update: Lung Cancer, Head and Neck Cancer, and the Cost of Immunotherapy

On Friday, May 31, the 2019 annual meeting of the American Society of Clinical Oncology (ASCO19) kicked off at McCormick Place in Chicago. Among the topics discussed were a bispecific antibody for lung cancer, immunotherapy combinations for head and neck cancer, and a way to potentially lower the cost of treatment with PD-1 blockade immunotherapies.

Eric B. Haura, MD, of Moffitt Cancer Center, focused on JNJ-372, a bispecific antibody that targets two cancer-related pathways—EGFR and cMet—in patients with advanced, non-small cell lung cancer (NSCLC) that is driven by mutated EGFR activity. As demonstrated in preclinical studies, this bispecific antibody has three mechanisms of action against cancer cells. First, it can inhibit signaling through the EGFR and cMet pathways; second, it can degrade the receptors for these pathways; and third, it can alert the immune system to eliminate the cancer cells bound by these bispecific antibodies.

Eric B. Haura, MD, of Moffitt Cancer Center, discusses JNJ-372, a bispecific antibody, at ASCO19.
Eric B. Haura, MD, discusses JNJ-372, a bispecific antibody, at ASCO19.

In a phase I trial (NCT02609776) in which 108 patients were treated with JNJ-372, 30% responded, and responses were seen in patients whose tumors had various types of EGFR mutations, including those who did not respond to targeted therapy with osimertinib, a targeted therapy against EGFR. Based on these results, this EGFR-and-cMet-targeting bispecific antibody is now being explored in a phase II trial.

Turning to head and neck cancer, Danny Rischin, M.D., of the Peter MacCallum Cancer Centre, discussed the combination of the PD-1 checkpoint immunotherapy pembrolizumab and chemotherapy as a first-line treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Danny Rischin, MD, of the Peter MacCallum Cancer Centre, discussed combination therapy at ASCO19.
Danny Rischin, MD, discussed combination therapy at ASCO19.

Compared to the standard-of-care for patients with head and neck cancer (the EXTREME regimen combining chemotherapy with the EGFR-targeting drug cetuximab), the immunotherapy-chemotherapy combination was associated with superior overall survival in a phase III trial (NCT02358031). At the three-year mark, 22.6% of patients who were treated with the combination were still alive, compared to only 10% of those who were treated with the EXTREME regimen.

The benefits of this combination were even more pronounced in patients whose tumors expressed PD-L1, especially patients with a Combined Positive Score of ≥ 20%, meaning at least 20 percent of their tumor cells expressed the PD-L1 molecule. In this group, the three-year overall survival rate was 33.2% (versus 8% for EXTREME), the progression-free survival rate at two years was 14.7% (versus 3.3% for EXTREME), and the duration of response was almost three months longer (7.1 months versus 4.2 months). Overall, Rischin said, “the data support pembrolizumab plus chemotherapy and pembrolizumab alone as new first-line standard-of-care therapies for recurrent or metastatic HNSCC.”

Renata Ferrarotto, MD, of the University of Texas MD Anderson Cancer Center, also focused on checkpoint immunotherapy in patients with a type of head and neck cancer known as oropharynx carcinoma. Ferrarotto discussed a phase I trial (NCT03144778) involving former CRI Clinical Team Leader Andrew G. Sikora, MD, PhD, of the Baylor College of Medicine, in which patients were treated with either the checkpoint immunotherapy combination of the PD-L1-blocking durvalumab and the CTLA-4-blocking tremelimumab or durvalumab alone prior to having their tumors surgically removed. In addition to evaluating the pre-surgical benefit of these immunotherapies, the study also sought to determine how levels of “killer” T cells within tumors affected outcomes as well as how the treatment altered those levels.

Renata Ferrarotto, MD, of the University of Texas MD Anderson Cancer Center, discusses checkpoint immunotherapy at ASCO19.
Renata Ferrarotto, MD, discusses checkpoint immunotherapy at ASCO19.

Overall, 43% of the patients treated with either both checkpoint immunotherapies or just PD-L1 checkpoint immunotherapy responded. The combination did not produce better response rates compared to PD-L1 immunotherapy alone. Furthermore, 32% of patients had major pathologic responses, meaning that less than 10% of their tumor mass remained viable. Ferrarotto also noted that the ratio of “killer” T cells in tumors after treatment compared to before treatment increased 3.6 fold in patients who had major pathologic responses, but not in patients who didn’t respond, indicating their role in patient responses.

Finally, Evan Hall, MD, M.Phil., of the Stanford University School of Medicine, discussed ways to lower costs associated with treatment with PD-1-targeting immunotherapies. He focused on pembrolizumab and nivolumab, which together saw $14 billion in sales in 2018, making them the second- and third-highest selling cancer drugs last year. The market for these drugs is significant. According to Hall, about 44% of all patients with advanced cancer in the United States are eligible to be treated with PD-1 checkpoint immunotherapy.

Evan Hall, MD, M.Phil., of the Stanford University School of Medicine, discussed ways to lower costs associated with treatment at ASCO19.
Evan Hall, MD, M.Phil., discussed ways to lower costs associated with treatment at ASCO19.

Due to current dosing strategies, however, much of these drugs are wasted each year, resulting in increased costs. Hall looked at how dose minimization strategies might be used to reduce this waste. In addition to fixed doses regardless of the individual patient, some doses are designed for patients based on how much they weigh. By going with the lower dose—whether it was based on the fixed dose or was weight-based—Hall explained how this could create significant cost savings.

Furthermore, Hall demonstrated how vial-sharing, in which leftover amounts of drug from one vial are used for subsequent patients rather than thrown out, could also lower costs. With pembrolizumab, which is only available in one, relatively large-sized vial in the U.S., this vial-sharing was shown to save more than $1 million per four-month period. These cost reductions were also more significant at the centers that treated higher numbers of patients, where the medicine could be administered more efficiently. Altogether, Hall suggested that these techniques could help save more than $1 billion per year globally.

There will be lots more exciting immunotherapy news coming out of ASCO19 in the days ahead. Be sure to follow our blog for these ASCO19 updates and remember to join our "Cancer Immunotherapy Insights from ASCO" Twitter chat (#CIMchat) on June 11, at 12pm ET, moderated by Sharon Begley, senior science writer at STAT.

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