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Checkpoint inhibitors and platinum as first line treatment for NSCLC

Combinations of immune checkpoint inhibitors and chemotherapy show promising results. Leena Gandhi will present the findings of the KEYNOTE 189 randomized, double-blind, placebo controlled phase 3 study.

Lung cancer is the leading cause for worldwide cancer mortality, with non small cell lung cancer (NSCLC) accounting for 80 to 85% of the cases. Platinum based chemotherapy is the long standing first line treatment regimen in patients with advanced NSCLC. The recent introduction and promising results of immune checkpoint inhibitors are challenging this treatment algorithm.

Immune checkpoint inhibitors as first line of treatment

Although overexpression of PD-L1 is an indicator of treatment success, new phase III studies show that all patients regardless of PD-1/PD-L1 status might profit from immune checkpoint inhibition. PD-1 and PD-L1 inhibitors will become the standard of care for the first line treatment of NSCLC patients. Together with radiation therapy the findings on combinations of immune checkpoint inhibition and chemotherapies will make it crucial to rethink treatment algorithms.

Pembrolizumab and nivolumab: promising results from phase I/II

The rationale behind combinations of chemotherapy and immune checkpoint inhibitors is the hypothesised immunological effect of chemotherapeutic agents. The signalling mechanisms triggered by chemotherapies is currently unknown.

In phase I/II pembrolizumab with carboplatin and paclitaxel, carboplatin, paclitaxel and bevacizumab, or carboplatin and pemetrexed showed no significant adverse effects, the objective response rate was 52%. The combination of carboplatin-pemetrexed-pembrolizumab in this phase proved most promising with an objective response rate of 70%. These results were independent of PD-L1 expression.

Similar to this treatment regimen nivolumab was combined with platinum based chemotherapy in patients with squamous histology. The results show low frequencies of progressive disease, higher ORR and longer stable disease.

Results to be expected at AACR

In phase III, the KEYNOTE 189 study explores a regimen of carboplatin or cisplatin and pemetrexed, and carboplatin-paclitaxel or nab-paclitaxel, with or without pembrolizumab in patients with nonsquamous and squamous NSCLC, respectively. Results are to presented at the AACR.

Session Link

Reference

Lazzari et al Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer? Ther Adv Med Oncol 2018, Vol. 10: 1­–12 https://doi.org/10.1177/1758835918762094

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