Combining the old and the new – Can combination therapy improve cancer treatment?

This study looked at combining therapies designed to stimulate the immune system with chemotherapy to treat patients with advanced lung cancer. The authors concluded that a combination of immune checkpoint inhibitors and chemotherapy is effective and tolerable at treating these patients.

Many tumor cells have proteins (PD-L1 and CTLA4) which stop the immune system from killing them. New therapies are available that block either PD-L1 or CTLA4, which allows the immune system to kill the cancer cells. These drugs are called immune checkpoint inhibitors. Anti-PD-L1 therapies include atezolizumab (Tecentriq), pembrolizumab (Keytruda) and nivolumab (Opdivo). Anti-CTLA4 therapies include ipilimumab (Yervoy).

Anti-PD-L1 treatments have been shown to be effective at treating patients with advanced lung cancer. It is possible that combining anti-PD-L1 drugs with an anti-CTLA4 drug or chemotherapy could improve outcomes for patients with advanced lung cancer.

This study aimed to determine the effectiveness and safety of combining immune checkpoint inhibitors with chemotherapy to treat patients with advanced lung cancer.  

The authors combined the data from 12 studies including 1514 patients. The 1-year overall survival rate (OS, survival rate one year after treatment), the 6-month progression free survival rate (PFS, rate of disease progression 6 months after treatment), the disease control rate (DCR, percentage of patients who responded to treatment) and overall response rate (ORR, percentage of patients with a reduction in tumor size) were determined.

9 of the studies examined patients with non-small-cell lung cancer (NSCLC). Treatment with a combination of immune checkpoint inhibitors and chemotherapy resulted in an average of 47% ORR, 81% DCR, 50.2% PFS and 56.4% OS. There was a 16% improvement in PFS in patients treated with combination therapy compared to chemotherapy alone.

3 studies included patients with small-cell lung cancer (SCLC). Treating these patients with a combination of immune checkpoint inhibitors and chemotherapy resulted in an average of 30.7% PFS and 36.9% OS. There was a 14% improvement in PFS in patients treated with combination therapy compared to chemotherapy alone. Specifically, combining anti-CTLA4 therapy and chemotherapy resulted in an average ORR of 65.4% and DCR of 87.6%.

Combining anti-PD-L1 and anti-CTLA4 treatments resulted in an average 29.6% ORR and 48.7% DCR for patients with NSCLC.

For patients treated with chemotherapy alone, the average PFS was 49.2%, DCR was 88.3% and ORR was 41.3%.

The most common side effects of combination therapy were decreased appetite, nausea, fatigue, hair loss, anemia (low iron) and neutropenia (low immune cell count).

The authors concluded that a combination therapy of immune checkpoint inhibitors and chemotherapy is effective and tolerable at treating patients with advanced lung cancer.