- In October 2016, atezumab was approved for second-line treatment of metastatic NSCLC in the United States, making it the first and so far the only anti-PD-L1 immunologic drug approved by the FDA for the treatment of metastatic NSCLC.
- Fresh from the IMpower131 study at the 2018 American Society of Clinical Oncology Annual Meeting: first-line combination chemotherapy (carboplatin + albumin-bound paclitaxel) with atezumab reduced the risk of cancer progression and death better than chemotherapy alone.
Among the many treatments for lung cancer, immunotherapy, a “latecomer”, has been a strong performer.
Atezolizumab (known as Tecentriq) is one of these rising “stars”. It is a PD-L1 antibody, known as programmed death-Ligand -1 (PD-L1), which competes with PD-1 to bind PD-L1 on the surface of tumor cells, thus blocking the binding of PD-L1 to PD-1 and restoring anti-tumor activity by relieving tumor suppression of immune cells.
Studies have confirmed that atezumab can not only treat advanced or metastatic non-small cell lung cancer (NSCLC) alone, but also in combination with other drugs, even in single-agent first-line therapy, and has demonstrated efficacy.
Crossover to secure second-line treatment
In October 2016, atezumab was approved in the United States for second-line treatment of metastatic NSCLC, making it the first and so far the only anti-PD-L1 immune drug approved by the US Food and Drug Administration (FDA) for the treatment of metastatic NSCLC.
The American Society of Clinical Oncology noted in the 2017 edition of the Stage IV NSCLC Guidelines that atezumab is indicated in stage IV NSCLC that has received first-line chemotherapy, has not received immunotherapy, has no contraindications to immunotherapy, and has positive PD-L1 expression (no less than 1%).
The National Comprehensive Cancer Network (NCCN) recommends atezumab for follow-up after first-line therapy for patients with PD-L1-expressing positive NSCLC in its 2018 update of the NSCLC guidelines.
The above recommendations from the authoritative guidelines are based primarily on the results of two studies, POPLAR and OAK.
The POPLAR study showed that in previously treated patients with advanced or metastatic NSCLC, atezumab prolonged median survival by 2.9 months and reduced the risk of death by 27% compared with docetaxel, a definitive chemotherapy agent, and that atezumab alone had fewer adverse effects than docetaxel.
The OAK study further solidified the results of the POPLAR study. Compared with docetaxel, atezumab was not only effective in those with positive PD-L1 expression, but also in those with low or no PD-L1 expression, extending survival by 3.7 months and reducing the risk of death by 25%; there was a significant benefit in patients with both nonsquamous and squamous cancers.
Going high, into first-line therapy
Atezumab also performed well in stage IV nonsquamous NSCLC, and the IMpower150 study showed that first-line combination chemotherapy (bevacizumab + carboplatin + paclitaxel) resulted in a significant benefit, with a median overall survival of 19.2 months and a 22% reduction in the risk of death, independent of PD-L1 expression, EGFR/ALK mutation, and liver metastasis, and other factors.
For patients with stage IV squamous NSCLC, there is also good news. At the 2018 American Society of Clinical Oncology Annual Meeting, the results of the IMpower131 study were fresh: first-line combination chemotherapy with atezumab (carboplatin + albumin-bound paclitaxel) reduced the risk of cancer progression and death better than chemotherapy alone. In addition, at month 12 of treatment, 24.7% of patients in the combination group did not experience disease progression, much more than the 12.0% in the chemotherapy alone group.
The BIRCH study of patients with locally progressive or metastatic NSCLC without CNS involvement and no history of chemotherapy showed good and durable clinical outcomes with atezumab monotherapy over the 2-year study period until the end of 2017, regardless of EGFR and KRAS gene mutations.
The future looks bright.
The future is promising, and more studies are underway
In addition to the studies mentioned above, a series of clinical trials of atezumab in NSCLC are ongoing. There is also a study (IMpower133) starting to explore the therapeutic effects of atezumab in small cell lung cancer (SCLC).
| Table 1 Ongoing clinical trials related to Atezolizumab lung cancer | ||
| Trial name | Patient Conditions | Comparative protocol |
| IMpower110 | Stage IV NACLC (squamous or non-squamous) |
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| IMpower111 | Stage IV NSCLC (squamous carcinoma) |
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| IMpower130 | Stage IV NSCLC (non-squamous) |
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| IMpower131 | Stage IV NSCLC (squamous carcinoma) |
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| IMpower132 | Stage IV NSCLC (non-squamous) on initial treatment |
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| IMpower133 | Untreated ES-SCLC |
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| IMpower150 | Stage IV NSCLC (non-squamous) |
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| IMpower210 | Locally advanced or metastatic NSCLC |
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Summary
Now that atezumab is officially approved and guideline-recommended as second-line therapy for patients with advanced NSCLC, it has the power to be a first-line therapy in combination with chemotherapy, and is expected to be another “light” on the road to life for patients with advanced lung cancer. “