Frontline Opdivo, Yervoy May Improve Survival in Non-Small Cell Lung Cancer

First-line treatment with Opdivo (nivolumab) plus low-dose Yervoy (ipilimumab) improved survival among patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, according to results from the CheckMate-227 trial reported at the European Society of Medical Oncology (ESMO) Congress 2019.

Moreover, these results could offer a chemotherapy-free first-line option for these patients, according to study author Dr. Solange Peters, from the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

“In my opinion these data are practice changing. CheckMate-227 is the first trial showing that the combination of nivolumab and ipilimumab prolongs survival as compared to chemotherapy in treatment-naïve patients with metastatic NSCLC,” Peters said in a press release issued by ESMO. “We already have several front-line treatment options for these patients, including chemotherapy combined with an anti-PD1 agent or an anti-PDL1 agent alone. And now we have a chemotherapy-sparing option of nivolumab plus ipilimumab.”

The global phase 3 CheckMate-227 study evaluated the first-line use of Opdivo in combination with Yervoy in im patients with stage 4 or recurrent NSCLC who had received no previous treatment.

In part one of the study, investigated different Opdivo-based regimens compared with chemotherapy in two different PD-L1 subgroups: 1,189 patients with PD-L1 expression of at least 1% and 550 patients with PD-L1 less than 1%. Patients with PD-L1 expression of at least 1% were treated with either Opdivo plus low-dose Yervoy, Opdivo alone or histology-based chemotherapy and those with PD-L1 less than 1% were treated with either Opdivo plus low-dose Yervoy, Opdivo plus chemotherapy or chemotherapy.

Patients treated with Opdivo plus Yervoy experienced significantly longer overall survival compared with those who were treated with chemotherapy.Moreover, patients with PD-L1 expression of 1% or more treated with Opdivo plus Yervoy had a median overall survival of 17.1 months, compared to 14.9 months in the chemotherapy group.

Patients with PD-L1less than 1% also showed an overall survival benefit, compared with chemotherapy.

In addition, progression-free survival (the time from treatment to disease progression), objective response rates (including complete and partial responses) and duration of response were all greater with the combination compared with chemotherapy.

Grade 3-4 treatment-related side effects across all patients occurred in 33% of those treated with the combination, 19% of those treated with Opdivo and 36% with chemotherapy.

“We used a low dose of ipilimumab (1 mg every six weeks) to make it tolerable,” Peters said. “Doing this led to a low rate of discontinuation and treatment-related toxicities or deaths. So, it’s a highly manageable treatment.”

Peters also noted that the next step will be to develop an algorithm to select the best front-line treatment for each patient. “We need to wait for a little more time to see which treatment really gives rise to improved long-term survival. The five-year survival from trials with these treatments will teach us if any of the options are better than others,” he said, adding that comparing toxicities across treatment arms will also be important. “We can then have an informed discussion with our patients.”