Onartuzumab plus erlotinib was associated with improved PFS and OS in the MET-positive population. These results combined with the worse outcomes observed in MET-negative patients treated with onartuzumab highlight the importance of diagnostic testing in drug development.

No abstract

No abstract

No abstract

Introduction Therapeutic antibodies to immune checkpoints show promising results. Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD-L1 receptor (programmed death 1). We investigated PD-L1 protein expression and messenger RNA (mRNA) levels in SCLC. Methods PD-L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28-8 PD-L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor-infiltrating immune cells (TIICs) obtained from a limited-disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive-disease SCLC was assessed for PD-L1 protein expression in tumor cells with Dako 28-8 antibody only. Results The overall prevalence of PD-L1 protein expression in tumor cells was 16.5%. In the limited-disease cohort, the prevalences of PD-L1 protein expression in tumor cells with SP142 and Dako 28-8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD-L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD-L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive-disease cohort demonstrated a 14.9% positivity of PD-L1 protein expression in tumor cells with Dako 28-8 antibody. Conclusions A subset of SCLCs is characterized by positive PD-L1 and/or mRNA expression in tumor cells. Higher PD-L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD-L1 in SCLC is lower than that published for NSCLC. The predictive role of PD-L1 expression in SCLC treatment remains to be established.

• Frontline brentuximab vedotin monotherapy provided a 92% ORR and was generally well tolerated in elderly HL patients.Outcomes in older patients with Hodgkin lymphoma (HL) tend to be poor following conventional chemotherapy regimens. Treatment-related toxicity is significant and comorbidities often limit therapeutic options. This phase 2, open-label study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, as frontline therapy in 27 HL patients aged ‡60 years. The objective response rate (ORR) was 92%, with 73% achieving complete remission. All patients achieved stable disease or better, and had decreased tumor volume following treatment. At the time of this analysis, the median duration of objective response for efficacy-evaluable patients (N 5 26) was 9.1 months (range, 2.8 to 20.91 months), median progression-free survival was 10.5 months (range, 2.61 to 22.31 months), and median overall survival had not been reached (range, 4.61 to 24.91 months). The observed adverse events (AEs) were generally consistent with the known safety profile of brentuximab vedotin. The most common AEs were peripheral sensory neuropathy (78%), fatigue (44%), and nausea (44%), and were £ grade 2 for most patients. The incidence of grade 3 peripheral neuropathy events was relatively high (30% overall), particularly among patients with the known risk factors of diabetes and/or hypothyroidism (46% vs 14% for those without). However, these risk factors were not associated with delayed time to resolution/improvement of peripheral neuropathy. Preliminary data showed no substantial age-related changes in brentuximab vedotin pharmacokinetics. Brentuximab vedotin monotherapy may provide a frontline treatment option for older patients who cannot tolerate conventional combination chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01716806. (Blood. 2015;126(26):2798-2804

No abstract

Trilaciclib is an intravenous CDK4/6 inhibitor administered prior to chemotherapy to preserve haematopoietic stem and progenitor cells and immune system function from chemotherapy‐induced damage (myelopreservation). The effects of administering trilaciclib prior to carboplatin, etoposide and atezolizumab (E/P/A) were evaluated in a randomised, double‐blind, placebo‐controlled Phase II study in patients with newly diagnosed extensive‐stage small cell lung cancer (ES‐SCLC) (NCT03041311). The primary endpoints were duration of severe neutropenia (SN; defined as absolute neutrophil count <0.5 × 109 cells per L) in Cycle 1 and occurrence of SN during the treatment period. Other endpoints were prespecified to assess the effects of trilaciclib on additional measures of myelopreservation, patient‐reported outcomes, antitumour efficacy and safety. Fifty‐two patients received trilaciclib prior to E/P/A and 53 patients received placebo. Compared to placebo, administration of trilaciclib resulted in statistically significant decreases in the mean duration of SN in Cycle 1 (0 vs 4 days; P < .0001) and occurrence of SN (1.9% vs 49.1%; P < .0001), with additional improvements in red blood cell and platelet measures and health‐related quality of life (HRQoL). Trilaciclib was well tolerated, with fewer grade ≥3 adverse events compared with placebo, primarily due to less high‐grade haematological toxicity. Antitumour efficacy outcomes were comparable. Administration of trilaciclib vs placebo generated more newly expanded peripheral T‐cell clones (P = .019), with significantly greater expansion among patients with an antitumour response to E/P/A (P = .002). Compared with placebo, trilaciclib administered prior to E/P/A improved patients' experience of receiving treatment for ES‐SCLC, as shown by reduced myelosuppression, and improved HRQoL and safety profiles.