Immunotherapy Managed to Knock Out Chemotherapy in Lung Cancer Treatment!

ASCO 2018 featured an important study in advanced (stage 4) non-small cell lung cancer (NSCLC). In most patients, even with minimally positive PD-L1, the immunotherapy pembrolizumab (Keytruda) was superior to chemotherapy as first-line treatment.

Oncology professionals considered the results of this study a true milestone .

PD-L1 expression (expression level) of only 1% or higher was associated with approximately 20% better overall survival with pembrolizumab than with chemotherapy.

On 24 October 2016, the American Food and Drug Administration, FDA approved pembrolizumab immunotherapy for stage 4 non-small cell lung cancer as first-line treatment, pembrolizumab immunotherapy was approved, but only for patients with 50% or greater tumor PD-L1 expression.

As levels of PD-L1, a cell-surface protein that prevents the immune system from recognizing cancer cells as foreign, increase, the response to these PD-L1-inhibiting immunotherapies also increases. Patients with PD-L1 positivity of 20% or higher who received immunotherapy had 23% better overall survival than chemotherapy recipients; correspondingly, those with PD-L1 levels of 50% or higher had 31% better overall survival.

Furthermore, involving more than 1250 patients with advanced non-small cell lung cancer, this KEYNOTE-042 study, a clinical trial, showed that immunotherapy more than doubled the overall duration of treatment response, regardless of PD-L1 expression level.

Patients given pembrolizumab as first-line treatment also experienced fewer side effects than those treated with chemotherapy; indeed, grade-3 (serious) side effects were less than half as frequent. Since treatment side effects are also an important cause of lung cancer deaths, immunotherapies promise a double benefit through both fewer side effects and a significant tumor-shrinking effect.

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With the immunotherapy studies in lung cancer that attracted attention after 2016, we can now say for patients with non-small cell lung cancer that the era in which chemotherapy was the only choice for starting treatment has ended.

However, many studies in lung cancer have also shown that immunotherapies may be effective as second-line treatment regardless of PD-L1 level.

Study Details

The 1274 patients were randomly assigned to two groups in a 1-to-1 ratio. As initial treatment for these lung cancer patients, one group received pembrolizumab every 3 weeks at a dose of 200 mg, while the other received a choice of carboplatin plus paclitaxel or carboplatin plus pemetrexed .

One of the most important features of this study is that crossover , meaning switching to the other therapy, was not allowed for any patients in the treatment groups. This contrasts with lung cancer clinical trials testing the other immunotherapy drug nivolumab (Opdivo).

Study Results

PD-L1 expression in 599 patients was 50% or higher, and in 818 patients was 20% or higher. After a median follow-up of 12.8 months, 13.7% of patients were still receiving pembrolizumab and 4.9% maintenance chemotherapy.

The results showed significantly better overall survival with pembrolizumab than chemotherapy at all levels of PD-L1 expression.

At ASCO, we saw new studies combining chemotherapy and immunotherapies. In May 2018, NEJM published the KEYNOTE-189 study, whose results for pembrolizumab plus chemotherapy were even better than in this study. We believe combinations of immunotherapies with other immunotherapies may achieve better results in the coming years. "How suitable PD-L1 is as a biomarker " or "tumor mutation burden (TML) and whether it can be used together with other immune biomarkers such as this" remain important unanswered questions, and the introduction of immunotherapies into lung cancer treatment does not mean that all patients will be cured. Nevertheless, I consider this development an important milestone, because the era when chemotherapy was the only option for non-small cell lung cancer has ended.