The ASCO Daily News aims to bring you the most scientific coverage from the 2017 Annual Meeting. Here are some bite-sized articles from Sunday's ASCO Daily News coverage.
Poster Discussion Session (Abstract 9509)
First Author: Jason Alan Chesney, MD, PhD
In an open-label phase II trial, ipilimumab (I) in combination with talimogene laherparepvec (T), an HSV–1 based oncolytic virus designed to replicate and express GM-CSF specifically in tumor cells, led to improved ORR compared with I alone among patients with unresected stage IIIB-IV melanoma. This is the first study to examine the safety and efficacy of combining an oncolytic virus with a checkpoint inhibitor.
198 patients were randomly assigned either to receive intratumor injections of T along with four IV infusions of I (T+I; 98 patients) or I infusions alone (100 patients). The patients had tumors that showed no evidence of immunosuppression. They were followed until injectable tumors disappeared or there was disease progression or intolerance. The median time of follow-up was 68 and 58 weeks for the T+I and I alone groups, respectively.
The study met the primary endpoint, which was ORR based on immune-related response criteria. Among patients in the T+I group, the ORR was 38.8% compared with 18.0% among patients who only received I (odds ratio = 2.9; p = 0.002).
The secondary endpoints were duration of response, disease control rate (DCR), PFS, OS, and safety. In the T+I group, 89% of patients remain in response compared with 83% of patients in the I alone group. The DCR and PFS in the T+I and I alone arms were, respectively, 58.2% vs. 42.0% and 53.1% vs. 51.0%. OS is unknown. Among a subset of 190 patients (95 in each arm), the most common adverse events in the T+I and I alone arms were fatigue (59% vs. 42%), chills (53% vs. 3%), and diarrhea (42% vs. 35%).
Poster Session (Abstract 9550)
First Author: Abraham C.F. Leung, MD
Researchers used a modified 3 + 3 design for SD-101 that involved a dose escalation of 1, 2, 4, and 8 mg injected in a single tumor lesion once weekly for 4 weeks and then once every 3 weeks for seven doses in combination with 200 mg of intravenous pembrolizumab every 3 weeks. Investigators assessed tumor responses with RECIST version 1.1.
Approximately one-third (36%) of patients had received three or more prior lines of therapy; nine were anti–PD-1 naive, and 13 were anti–PD-1 experienced. At a median follow-up time of 97 days (maximum, 382 days), there was no dose-limiting toxicity.
Serious treatment-related AEs occurred in 59.1% of patients; myalgia and injection-site pain were the most common (13.6% each). Immune-related AEs occurred in two patients: a grade 2 pneumonitis on day 23 resulted in drug withdrawal, and a grade 3 hypophysitis occurred 85 days after the last treatment. There were no deaths.
Patients who were PD-1 inhibitor naive demonstrated response at the injected and noninjected lesions at all doses, with an ORR of 66.7%. Patients who were PD-1 inhibitor experienced demonstrated a response at the 8-mg dose, with one patient (7.7%) experiencing a partial response, and five patients (38.5%) demonstrating stable disease.
The investigators concluded that the combination of SD-101 and pembrolizumab was well-tolerated and has potential activity in both PD-1 inhibitor–naive and–experienced patients with metastatic melanoma.
Poster Session (Abstract 1039)
First Author: Richard S. Finn, MD
A subanalysis of the PALOMA-2 phase III study that compared palbociclib plus letrozole to placebo plus letrozole in women with ER-positive, HER2-negative advanced breast cancer found no significant differences in efficacy or adverse events (AEs) between subgroups.
666 postmenopausal women were randomly assigned in a 2-to-1 manner to receive oral palbociclib (125 mg daily; 3 weeks on, 1 week off) plus letrozole (2.5 mg daily) or placebo plus letrozole. Key endpoints were investigator-assessed PFS and safety.
As reported in 2016,1 the combination treatment nearly doubled the PFS compared with placebo plus letrozole (24.8 vs. 14.5 months; hazard ratio for disease progression or death was 0.58, 95% CI [0.46, 0.72]; p < 0.001). The most common grade 3 or 4 hematologic AEs in the combination arm compared with the placebo arm were neutropenia (66.4% vs. 1.4%), leukopenia (24.8% vs. 0%), thrombocytopenia (1.6% vs. 0%), and anemia (5.4% vs. 1.8%).
The subanalysis evaluated AEs across all subgroups, which included visceral compared with nonvisceral disease, prior hormone treatment, metastasis location, prior chemotherapy, ECOG performance status, and disease-free interval (> 12 vs. < 12 months). The median PFS improved in all subgroups treated with the combination compared with those treated with placebo plus letrozole, with no significant differences in AEs.
The authors concluded that palbociclib plus letrozole should be considered a first-line treatment for all patients with ER-positive, HER2-negative advanced breast cancer.
Patient and Survivor Care
Poster Discussion Session (Abstract LBA10012)
First Author: Mohammad Issam Abu Zaid, MBBS
According to the results of a multicenter center study, testicular cancer survivors (TCS) who experience hypogonadism (HG) following first-line, platinum-based chemotherapy are more likely to experience adverse health outcomes (AHO) including dyslipidemia and erectile dysfunction (ED).
The study included 491 TCS in North America younger than age 55 at diagnosis and between 19 and 68 when they were evaluated. The men had only received first-line chemotherapy after 1990. They were assessed for HG based on serum testosterone < 3.0 ng/mL or the use of testosterone replacement therapy, and answered questionnaires about 16 AHO and health behaviors.
Of the 38.5% of men in the study who had HG, only 35.0% reported having no or only one AHO, compared with 49.0% of the men who did not have HG. The men who had HG were more likely than the unaffected men to take medications for dyslipidemia (20% vs. 6%; p < 0.001), hypertension (19% vs. 11%; p = 0.01), erectile dysfunction (20% vs. 12%; p = 0.02), diabetes (6% vs. 3%; p = 0.07), anxiety/depression (15% vs. 10%; p = 0.06), and to report having peripheral neuropathy (31% vs. 23%; p = 0.04).
HG was more likely among TCS who were older (OR = 1.4 per 10-year increase; p = 0.007) and had BMI > 25 kg/m2 (OR = 2.2; p = 0.003), but less likely among those who engaged in vigorous physical activity (OR = 0.6; p = 0.06). Although the study supported previous research suggesting two SNPs in the sex-hormone-binding globulin locus are genetic risk factors for HG, it was not powered to confirm these associations.