Atezolizumab–platinum-based chemotherapy NSCLC regimens advance to phase III trials
medwireNews: Results from a phase Ib study indicate that atezolizumab could be feasible in combination with one of three different platinum-doublet regimens for patients with stage IIIb–IV non-small-cell lung cancer (NSCLC) without actionable genetic mutations.
The programmed cell death ligand 1 (PD-L1) inhibitor was given at a dose of 15 mg/kg every 3 weeks in combination with 4–6 cycles of carboplatin plus paclitaxel (arm C, n=25) or carboplatin plus nab-paclitaxel (arm E, n=26), or given alongside 4–6 cycles of carboplatin plus pemetrexed, with maintenance pemetrexed also permitted (arm D, n=25).
As reported at the 2017 annual meeting of the American Society of Clinical Oncology, held in Chicago, Illinois, USA, the most common grade 3–4 treatment-related toxicity in the three groups was neutropenia, affecting 36% of patients in arms C and D and 42% of those in arm E. Anemia was the second most common event, occurring in 16%, 16%, and 31% of patients, respectively.
Talking to medwireNews, lead author Stephen Liu, from Georgetown University in Washington DC, USA, said that all three combinations were “fairly well tolerated” and within the expected range of toxicities for platinum-based chemotherapy.
Two patients in arm D and one patient in each of arms C and E discontinued atezolizumab following treatment-emergent adverse events linked to the PD-L1 inhibitor. In all, seven patients in arm C and 10 patients in both arm D and arm E experienced any-grade AEs leading to treatment withdrawal.
Grade 5 pneumonia and pneumonitis were reported in one patient in arm C, although the pneumonitis occurred around 60 days after discontinuing atezolizumab and within 2 days of beginning crizotinib. One patient in arm D experienced grade 5 systemic candida infection, while another patient in arm E developed grade 5 autoimmune hepatitis more than 30 days after finishing treatment.
Median RECIST-defined progression-free survival in arms C, D and E were 7.1, 8.4, and 5.7 months, respectively, with corresponding median overall survival (OS) of 12.9, 18.9, and 17.0 months.
A complete RECIST response was reported for four (15%) patients in arm E and one (4%) patient in arm D, but none were reported in arm C. Partial responses occurred in 36% of arm C, 64% of arm D, and 31% of arm E. The disease control rates in arms C, D and E were 84%, 76%, and 73%, respectively, while the 12-month OS rates were 52%, 68%, and 69%.
In all, 41% of the patients had tumor or immune PD-L1 expression at baseline but there was no correlation between expression and OS.
Liu explained that as patients were not randomly assigned to treatment, the safety and survival results of the three trial arms cannot be directly compared. But he called the findings “very favorable” when compared with historical data for chemotherapy alone in this population, noting that the five complete responses achieved were “very compelling.”
He concluded that “without any major concerns, all three arms have moved onto randomised phase III studies,” with initial results from these IMpower130, IMpower131, IMpower132, and IMpower150 trials expected within a year.
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