Pembrolizumab Immunotherapy Found Effective with Chemotherapy as Initial Treatment for Stage 4 Lung Cancer

In April 2018, New England Journal of Medicine published KEYNOTE-189 findings that appear set to overturn a cornerstone lung cancer treatment approach. Pembrolizumab immunotherapy was effective with chemotherapy as initial treatment for metastatic (stage 4) non-small cell lung cancer.

Currently, patients with metastatic and non-small cell lung cancer are first tested for eligibility for targeted therapy . Eligible patients receive targeted medicines; ineligible patients in our country receive first-line platinum chemotherapy combined with another effective chemotherapy. These treatments aim to improve quality of life and extend survival. Chemotherapy alone in metastatic lung cancer provides average survival of approximately 1 year. This may be shorter with aggressive disease unresponsive to chemotherapy and longer in responders.

In metastatic lung cancer, immunotherapiesproved effective after 2016 in patients unresponsive to first-line chemotherapy or progressing during it, receiving FDA approval. Many studies showed success with different immunotherapy structures acting through similar mechanisms, making them available second line.

Although not yet approved for lung cancer in our country, early-access programs allowed us to treat many metastatic patients and gain experience. The most important observed advantage was easier, more manageable tolerability than chemotherapy. Positive experiences motivated us to enroll many patients in ongoing international clinical trials to access these approaches.

In 2017, the published KEYNOTE-024 study examined PD-L1 levels of %50 or higher defined patients whose initial chemotherapy was compared with immunotherapy. Immunotherapy produced tumor response in %50 and superior disease control and survival. This was rapidly accepted, and pembrolizumab (Keytruda) received FDA approval to replace chemotherapy alone as first-line treatment for metastatic non-small cell lung cancer with PDL-1 levels ≥%50. However, PDL-1 ≥%50 patients represented fewer than 1/3 of the total.

After these positive developments, our shared question was, “Can immunotherapy and chemotherapy be combined first line in metastatic non-small cell lung cancer regardless of PD-L1 level?” as the next challenge.

KEYNOTE-189 answered this question, and favorable results regardless of PD-L1 levels led health news worldwide.

The study included metastatic nonsquamous non-small cell lung cancer patients totaling 614, randomized 2:1.

One group received platinum and pemetrexed chemotherapy, while the experimental arm received the same chemotherapy plus pembrolizumab (Keytruda) at a fixed 200 mg dose. Both groups received four combination cycles, then stopped platinum. After four cycles, standard treatment continued pemetrexed, while the experimental group continued pemetrexed and pembrolizumab.

Study Results

Response rates were %48 with immunotherapy versus %19 with chemotherapy. Median disease control was 8.8 months versus 4.9 with standard treatment. At approximately 10 months' median follow-up, %10 more patients in the immunotherapy arm were alive.

The immunotherapy-chemotherapy combination significantly surpassed standard chemotherapy in response, disease control duration and survival.

Commentary

New-generation immunotherapies introduced into oncology over the past 10 years have produced encouraging results in common cancers such as lung cancer, where chemotherapy outcomes were often unsatisfactory. We will follow long-term trial results, FDA approval and approval processes in our country.

We recommend newly diagnosed metastatic non-small cell lung cancer patients and families ask their doctors whether a suitable clinical trial is available in our country when discussing treatment plans.

Related Topics:

• 4 Tips for Quitting Smoking — Current Approaches
• Innovations in Lung Cancer Treatment — 2017 and 2018
• What Are Lung Cancer Metastasis Symptoms?
• Who Can Join Clinical Trials to Access New Medicines? What Is the Situation in Our Country?