1. Fuerst, Mark L.

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CHICAGO-Patients with advanced squamous non-small cell lung cancer (NSCLC) benefit more from initial treatment with the PD-L1 inhibitor atezolizumab plus chemotherapy than from chemotherapy alone, according to a new study.

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Squamous NSCLC is difficult to treat and there have been limited new treatment options over the past several decades. Approximately 25-30 percent of patients with NSCLC have tumors that can be classified as squamous. First-line standard of care for patients with advanced squamous NSCLC includes platinum-based chemotherapy regimens. Less than 15 percent of people with advanced squamous NSCLC survive a year after diagnosis, and less than 2 percent survive 5 years.


"Patients treated with first-line carboplatin plus nab-paclitaxel have a median progression-free survival (PFS) of 5.6 months and median overall survival (OS) of 10.7 months with an objective response rate (ORR) of 41 percent," said lead author Robert M. Jotte, MD, PhD, Medical Director and Co-Chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver. He presented the results of the study at a press briefing at the 2018 ASCO Annual Meeting (Abstract LBA9000).


"Our findings may provide a new potential treatment option for this type of cancer. We used to think that chemotherapy just knocked down the patient's immune system and that it would be irrational to combine it with immunotherapy; but growing research, including this study, shows that chemotherapy can help trigger the immune response to the tumor, helping the immunotherapy treatment work better," said Jotte, who noted that recent studies have found a benefit of combining immunotherapy with chemotherapy in non-squamous lung cancer.


The IMpower131 trial enrolled 1,021 patients with stage IV squamous NSCLC. Tumors were tested for PD-L1 expression, but patients were included in the trial regardless of tumor PD-L1 expression level. Patients with EGFR or ALK gene changes in the tumor received targeted treatments before starting therapy.


The 1,021 participants were randomly assigned to one of three treatment groups. Jotte presented data on outcomes for only two of the groups: atezolizumab plus chemotherapy with carboplatin and nab-paclitaxel (343 patients) and chemotherapy with carboplatin and nab-paclitaxel (340 patients). Outcome data are not yet available for the third treatment group, which received atezolizumab plus chemotherapy with carboplatin and paclitaxel.


Key Findings

Overall, the results show 29 percent of patients, regardless of PD-L1 expression, had a reduced risk of disease worsening or death, compared with those who received chemotherapy alone.


Importantly, there was "a doubling of the 12-month landmark PFS rate for patients treated with atezolizumab plus chemotherapy (24.7%) versus chemotherapy alone (12%)," Jotte noted.


The PFS benefit with atezolizumab plus chemotherapy was observed across all PD-L1 subgroups, including those with PD-L1-negative tumors and liver metastases, he said. Similarly, "an increase in confirmed ORR and duration of response in atezolizumab plus chemotherapy versus chemotherapy was observed across all PD-L1 subgroups."


OS data are not yet mature. At this interim analysis, a statistically significant median OS benefit was not observed for atezolizumab plus chemotherapy (14 months) as compared to chemotherapy alone (13.9 months). Jotte said follow-up will continue with another analysis of the data expected later this year.


The rate of severe side effects was higher with the combined immunotherapy-chemotherapy treatment (68%) than with chemotherapy alone (57%). Jotte said the safety profile was manageable, and the safety risks were consistent with those known for the individual therapies. The most common side effects of atezolizumab included skin rash, colitis, and low thyroid hormone.


This is the first phase III trial of an immunotherapy-based combined modality treatment to show a significant improvement in PFS in advanced squamous NSCLC. Although the difference between treatment groups is modest, a statistically significant improvement shows that patients with advanced squamous lung cancer can benefit with the addition of immunotherapy to standard treatment.


More research is needed to determine which patients benefit the most from the addition of immunotherapy. The researchers plan to explore tumor PD-L1 expression and other molecular markers, including tumor mutational burden.


In conclusion, Jotte stated: "IMpower131 data show that patients with advanced squamous NSCLC benefit more from initial treatment with atezolizumab plus chemotherapy than from chemotherapy alone. Some 29 percent of patients had a reduced risk of their disease worsening or death with the combination versus chemotherapy alone. Cancer had not worsened in 24.7 percent of patients receiving atezolizumab plus chemotherapy, compared with 12 percent of those receiving chemotherapy alone. This PFS benefit was observed across all-comers (all PD-L1 expressing subgroups) and was enriched in subgroups with higher PD-L1 expression."


ASCO Expert David L. Graham, MD, Physician Administrator at Levine Cancer Institute in Charlotte, N.C., commented: "This is one more example of how immunotherapy is making steady gains against a number of cancers. Immunotherapy has been shown to be effective in other types of lung cancer, and now we're seeing encouraging improvements in advanced squamous lung cancer, which historically has been very difficult to treat.


"I hope this translates to an OS benefit. If it does, we will have a new standard of care for squamous NSCLC."


Mark L. Fuerst is a contributing writer.