Four-Drug Combination Improves NSCLC Outcomes

A four-drug combination, including Tecentriq (atezolizumab), Avastin (bevacizumab), carboplatin and paclitaxel, delayed progression or death by 38 percent in patients with advanced non-squamous non—small cell lung cancer (NSCLC), compared to those who were treated with Avastin alone, according to findings from the phase 3 IMpower150 trial presented at the ESMO Immuno Oncology Congress.

In the study, the Tecentriq regimen demonstrated a median progression-free survival (PFS) of 8.3 months compared with 6.8 months with Avastin and chemotherapy alone. The 12-month PFS rate was 37 percent with the Tecentriq-containing regimen and 18 percent with the bevacizumab/chemotherapy regimen.

In a preliminary examination of overall survival (OS), there was a 22.5 percent reduction in the risk of death with the Tecentriq combination compared with Avastin and chemotherapy alone. After a minimum follow-up of 9.5 months, the median OS was 14.4 versus 19.2 months, in favor of the Tecentriq group. The next OS analysis will take place in the first half of 2018.

“This is the first phase 3 trial to report on the combination of chemotherapy, antiangiogenic treatment and immunotherapy as first line treatment for advanced non-squamous NSCLC,” said lead author Martin Reck, M.D., chief oncology physician, Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. “The trial met its co-primary endpoint of PFS and the preliminary results of the co-primary endpoint of overall survival, although immature, look encouraging.”

The IMpower150 study enrolled 1202 patients with stage 4 non-squamous NSCLC. Patients were randomized evenly to receive Tecentriq plus carboplatin and paclitaxel (arm A), Tecentriq with Avastin plus carboplatin and paclitaxel (arm B), or Avastin plus carboplatin and paclitaxel (arm C). Those with known EGFR or ALK alterations were excluded from the study. Patients were also tested for a tumor T-effector gene expression signature.

In the investigational arms, Tecentriq was administered at 1,200 mg intravenously every three weeks and Avastin was given at 15 mg/kg. In each arm, carboplatin and paclitaxel were given on day 1 of each cycle for four to six cycles. In arm A, maintenance therapy was given with Tecentriq alone and in arm B patients received maintenance therapy with the combination of Avastin and Tecentriq. In arm C, maintenance was given with Avastin alone.

The median age of patients in the trial was 63 years and 60 percent were previous smokers. Overall, most patients were male and the ECOG performance status was 0 for 39 percent of patients in arm B and for 43 percent in arm C. The minimum follow-up at the time of the analysis was 9.5 months. For the interim analysis, the study was only designed to compare arms B and C.

The objective response rate (ORR) in the Tecentriq arm was 64 percent compared with 48 percent in the bevacizumab/chemotherapy alone group. PD-L1 expression on immune and tumor cells did not appear to impact efficacy, as those testing negative for the marker still experienced an improvement in PFS with Tecentriq. However, there was a 50 percent reduction in the risk of progression or death with Tecentriq in those testing positive for PD-L1 on immune and tumor cells.

“There was a significant and clinically relevant improvement in progression-free survival favoring the addition of atezolizumab to bevacizumab and chemotherapy," said Reck. "The results show that there is a way to improve the efficacy of platinum-based chemotherapy in patients with advanced non-squamous NSCLC."

In the T-effector signature wild-type population, the addition of Tecentriq reduced the risk of progression or death by 49 percent. The median PFS was 11.3 months with the PD-L1 inhibitor versus 6.8 months with Avastin /chemotherapy alone. The ORR in this group was 69 percent with Tecentriq compared with 54 percent without the PD-L1 inhibitor. The 12-month PFS rate was 18 percent with bevacizumab/chemotherapy and 46 percent with the addition of Tecentriq.

Each of the agents showed similar toxicity profiles as in previous trials. Serious treatment-related adverse events were observed in 25.4 percent of patients treated with the Tecentriq regimen compared with 19.3 percent of those in the control arm. "There were no new safety signals or toxicity issues with this combination so it appears to be a feasible approach for this group of patients," Reck noted.

Preliminary findings were also presented for the comparison of arm A (Tecentriq plus chemotherapy without Avastin) with the control arm of Avastin plus chemotherapy (arm C). In this analysis, there was not a benefit seen in PFS for Tecentriq. Additionally, ORR was similar between the two groups (49 percent vs 48 percent). Data for this comparison continue to mature for OS.

“This Tecentriq study is the first positive phase 3 combination trial that showed a cancer immunotherapy reduced the risk of the disease getting worse when used as an initial treatment in a broad group of people with advanced non-squamous NSCLC,” Sandra Horning, M.D., chief medical officer and Head of Global Product Development at Roche, the company developing the drugs. “The IMpower150 study represents an important advance in lung cancer treatment, and we will submit these results to regulatory authorities around the world to potentially bring a new standard of care to people living with this disease as soon as possible.”

Tecentriq is currently approved as a treatment for patients with metastatic NSCLC following progression on a platinum-containing regimen. For lung cancer, Avastin is approved for patients with non-squamous NSCLC in combination with carboplatin and paclitaxel.

Several studies continue to assess Tecentriq as a treatment for patients with lung cancer as part of various combinations or as monotherapy. The PD-L1 inhibitor is being looked at with Abraxane (nab-paclitaxel) and in combinations with pemetrexed and other chemotherapy agents. The combination of Tecentriq and Avastin is being assessed in several solid tumors, with promising findings presented in renal cell carcinoma. Trial looking at this combination are currently ongoing.