No abstract

Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-boundpaclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumabepaclitaxel in aTNBC. Patients and methods: Eligible patients [no prior systemic therapy or 12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m 2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression 1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P ¼ 0.20; median PFS 6.0 months with atezolizumabepaclitaxel versus 5.7 months with placeboepaclitaxel]. In the PD-L1-positive population, atezolizumabepaclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placeboepaclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumabepaclitaxel versus 28.3 months with placeboe paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov: NCT03125902.

ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.

GISTs with an identical KIT or PDGFRA mutation may have widely varying risks for recurrence. Most of the patients with PDGFRA mutations and those with KIT exon 11 duplication mutation or deletion of one codon have favorable RFS with surgery alone and are usually not candidates for adjuvant therapy.