Opdivo Improves Overall Survival, Objective Response Rate in Head and Neck Cancer

Treatment with single-agent Opdivo (nivolumab) improved overall survival (OS) and objective response rates (ORR) compared with investigator's choice of therapy for patients with recurrent or metastatic head and neck squamous cell carcinoma (SCCHN), according data from the phase 3 CheckMate-141 study presented at the 2016 annual meeting of the American Society of Clinical Oncology (ASCO), a gathering of over 30,000 oncology professionals in Chicago.

Across the full study, the median OS was 7.5 months compared with 5.1 months with investigator's choice. The median progression-free survival (PFS) was two months with Opdivo versus 2.3 months with investigator's choice. The objective response rate (ORR) was 13.3 percent with Opdivo and 5.8 percent for investigator's choice.

Further analysis revealed distinct populations of patients who responded better to Opdivo monotherapy, specifically those with PD-L1-positive and HPV-positive SCCHN. In these groups, the reduction in the risk of death with Opdivo was near 50 percent versus investigator's choice of therapy.

"Opdivo is a new standard-of-care option for patients with recurrent or metastatic head and neck squamous cell carcinoma after platinum-based therapy," said lead investigator Robert Ferris, from the University of Pittsburgh Medical Center Cancer Center. "Opdivo is the first agent to demonstrate a significant improvement in survival in patients with head and neck squamous cell carcinoma who progress after platinum-based therapy in a global, phase 3 comparative trial."

In the trial, 361 patients with cancer of the oral cavity, pharynx or larynx were randomized. A total of 240 patients received Opdivo and 121 were given investigator's choice of Erbitux (cetuximab), methotrexate or docetaxel.

The median age of patients in the trial was 60 years, and 31.3 percent were 65 years of age or older. The majority of patients were Caucasian males and had an ECOG Performance Status of one. Most patients received two or more prior systemic therapies and over 90 percent had received prior radiation therapy. HPV status was known for 49.3 percent of patients and PD-L1 expression was available for 72 percent of enrolled patients.

The primary endpoint was OS, with secondary outcome measures focused on response rates and progression-free survival (PFS). The study was initiated in May 2014 and was not scheduled to complete until October 2016; however, it was stopped early after an independent monitoring panel determined the primary endpoint was met with the anti—PD-1 agent versus the investigator's choice of therapy.

The one-year OS rates were 36 percent with Opdivo compared with 16.6 percent for investigator’s choice. Similar improvements in survival were seen across demographic subgroups. The six-year PFS rates were 19.7 percent for Opdivo and 9.9 percent for investigator's choice of therapy.

The ORR in the Opdivo arm consisted of six complete responses and the stable disease (SD) rate was 22.9 percent. In the investigator's choice arm, one patient had a complete response and the SD rate was 35.5 percent. "Opdivo doubled the one-year survival rate, from 36 percent with Opdivo to 17 percent for investigator's choice of therapy," said Ferris. "Opdivo demonstrated a survival benefit in the overall study population, regardless of PD-L1 expression or p16 status."

Those with PD-L1 expression on one percent or greater of cells experienced a median OS of 8.7 months with Opdivo compared with 4.6 months in the control arm. Those who tested negative for PD-L1 had a median OS of 5.7 months with Opdivo versus 5.8 months in the control arm.

In those with PD-L1 expression on five percent or greater cells, the median OS was 8.8 versus 4.6 months for Opdivo and investigator's choice, respectively. For those with 10 percent or greater expression, median OS was and 8.7 versus 5.2 months, for Opdivo and the control, respectively.

"Magnitude of OS benefit of Opdivo versus investigator's choice was greater in patients expressing PD-L1, and increasing PD-L1 expression did not result in further benefit," said Ferris.

For those with one percent or greater PD-L1 expression, the median PFS was 2.1 months with Opdivo versus two months for investigator's choice. For the five percent or greater expression group, the median PFS with Opdivo was 3.2 months compared with two months in the comparator arm. In the 10 percent or greater expression group, median PFS was 2.1 versus 2.1 months, for Opdivo and the control, respectively.

In patients with tumors that expressed PD-L1 on one percent or greater of cells, the ORR was 17 percent with Opdivo compared with 1.6 percent with investigator's choice. In those with five percent or greater and 10 percent or greater expression, the ORRs were 22.2 percent versus 2.3 percent and 27.9 percent versus 2.9 percent, for Opdivo and the control arm, respectively. In the PD-L1-negative group, the ORR was 12.3 percent with Opdivo and 10.5 percent with investigator's choice of therapy.

HPV status also played a role in the responses experienced by patients treated with Opdivo. In the HPV-positive group, the median OS was 9.1 months with Opdivo compared with 4.4 months with investigator's choice. In the HPV-negative arm, the median OS with Opdivo was 7.5 versus 5.8 months.

Those with PD-L1 expression one percent or greater and HPV-positive SCCHN had a median OS of 8.8 months with Opdivo and 3.9 months in the control arm. In those with one percent or greater PD-L1 expression and HPV-negative disease, the median OS was 8.8 versus 5.6 months, for Opdivo and control, respectively.

For those with PD-L1-negative and HPV-positive disease, the median OS was 10 versus 6.4 months. In those with PD-L1-negative/HPV-negative SCCHN, the median OS was 7.1 months with Opdivo and 7.4 months with investigator's choice of therapy.

AEs were significantly less with Opdivo versus investigator's choice. Overall, grade 3/4 events were experienced by 13.1 percent of patients treated with Opdivo versus 35.1 percent for investigator’s choice. All-grade AEs were experienced by 58.9 percent of patients treated with Opdivo compared with 77.5 percent with investigator's choice. The most common grade 3/4 AEs with Opdivo were fatigue, anemia and asthenia. For investigator's choice, the most common grade 3/4 AEs were anemia, alopecia, fatigue, diarrhea, asthenia and mucosal inflammation.