“In a randomized phase II KEYNOTE-002 trial reported in The Lancet Oncology, Ribas et al found that treatment with the anti–PD-1 antibody pembrolizumab (Keytruda) prolonged progression-free survival vs investigator-choice chemotherapy in patients with advanced melanoma progressing on ipilimumab (Yervoy) and, if BRAF V600 mutant–positive, a BRAF or MEK inhibitor.
“The open-label trial included 540 patients from 12 countries with progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF V600 mutant–positive, previous treatment with a BRAF or MEK inhibitor or both. Patients were randomly assigned 1:1:1 between November 2012 and November 2013 to receive pembrolizumab 2 mg/kg (n = 180) or 10 mg/kg (n = 181) every 3 weeks or investigator-choice chemotherapy (n = 179, including 42 to paclitaxel plus carboplatin, 28 to paclitaxel, 13 to carboplatin, 45 to dacarbazine, and 43 to temozolomide)…
“The investigators concluded: ‘These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumab-refractory melanoma.’ “
“In the phase III BOLERO-1 trial, reported in The Lancet Oncology, Hurvitz et al found that the addition of the mTOR inhibitor everolimus (Afinitor) to trastuzumab (Herceptin)-paclitaxel did not significantly increase progression-free survival among patients with HER2-positive advanced breast cancer. A 7-month prolongation in progression-free survival was observed with everolimus among patients with hormone receptor–negative disease.”
“Statin use has been associated with improved outcome in prostate cancer. In a study reported in JAMA Oncology, Harshman et al found that statin use at the time of initiation of androgen-deprivation therapy was associated with prolonged time to progression during androgen-deprivation therapy in men with hormone-sensitive prostate cancer. The potential mechanism of this effect may be statin competitive inhibition of dehydroepiandrosterone sulfate (DHEAS) uptake.
“Androgen-deprivation therapy for biochemical or metastatic recurrence or new metastatic disease between January 1996 and November 2013 showed that 283 men (31%) were taking statins at the start of androgen-deprivation therapy. After a median follow-up of 5.8 years, 644 patients (70%) had disease progression while receiving androgen-deprivation therapy, with a median time to progression during androgen-deprivation therapy of 20.3 months. Median time to progression was 27.5 months (95% confidence interval [CI] = 21.1–37.7 months) in statin users vs 17.4 months (95% CI = 14.9–21.1 months) in nonusers (P < .001).”
“In the care of patients with metastatic breast cancer, the next new thing is the same old thing: paclitaxel (multiple brands).
“Results of the CALGB 40502/NCCTG N063H (Alliance) trial, first reported at the American Society of Clinical Oncology annual meeting in 2012 and published online June 8 in the Journal of Clinical Oncology, show that patients with advanced breast cancer had better median progression-free survival (PFS) with once-weekly paclitaxel than with ixabepilone (Ixempra, Bristol-Myers Squibb Company), a newer agent.
“In the third arm of the trial, paclitaxel was equivalent in its effect on PFS to its newer, more water-soluble cousin, nanoparticle alubimun-bound paclitaxel (nab-paclitaxel), and plain old paclitaxel was less toxic than either of its comparators.”
“The ALK and RET inhibitor alectinib yielded good response rates and was very well tolerated in a phase II trial of patients with advanced, ALK-positive non–small-cell lung cancer (NSCLC; abstract 8008). Results were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2, in Chicago.
“Crizotinib is currently the standard-of-care for advanced, treatment-naive ALK-positive NSCLC. ‘However, the median progression-free survival (PFS) for these patients on crizotinib is under 12 months,’ said Sai-Hong Ignatius Ou, MD, PhD, of the UC Irvine Medical Center in California. ‘This is in part due to development of ALK mutations that are resistant to crizotinib.’
“Alectinib is a next-generation inhibitor that is highly selective for ALK and RET; as an ALK inhibitor, Ou said, it is approximately five times as potent as crizotinib. It can inhibit the majority of clinically relevant acquired ALK mutations.”
“An immunotherapy combination for untreated melanoma reduced the risk of death or progression by more than half as compared with a drug currently used as a standard of care, a large randomized trial showed.
“Patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) had a median progression-free survival (PFS) of 11.5 months compared with 2.9 months for ipilimumab alone and 6.9 months with nivolumab monotherapy. Median PFS with the combination and with nivolumab alone increased to 14 months — more than four times greater than the PFS of patients who received only ipilimumab — among patients whose tumors tested positive for programmed death receptor ligand 1 (PD-L1), the target of nivolumab.
“The PFS improvement came at a price of increased toxicity, as grade 3/4 adverse events occurred twice as often with the combination as with ipilimumab monotherapy, but even patients who discontinued treatment because of side effects did better with the combination, as reported here at the American Society of Clinical Oncology meeting.”
“Assigning men in biological relapse after radical prostatectomy to combined salvage treatment with hormone therapy and radiation therapy significantly delayed disease progression compared with radiation therapy alone, according to the results of the GETUG-AFU 16 phase III trial (abstract 5006).
“ ‘Salvage radiotherapy combined with limited androgen deprivation therapy improves the 5-year progression-free survival rate compared to radiotherapy alone,’ said study presenter Christian Carrie, MD, of the department of radiation oncology at the University of Lyon-Centre Leon Berard. ‘There is no significant difference in overall survival, but the follow-up is still too short.’
“Between October 2006 and March 2010, 743 patients were enrolled in GETUG-AFU 16 and randomly assigned to radiation therapy alone (n = 374) or radiation plus hormone therapy with goserelin 10.8 mg for 6 months (n = 369). The primary endpoint of the trial was progression-free survival.”
“Immunomedics, Inc., (IMMU) today announced that among 49 patients with metastatic triple-negative breast cancer (TNBC) evaluated for response to treatments with sacituzumab govitecan in a mid-stage clinical study, 31%, or 15 patients, showed a reduction in tumor size of 30% or more. They include 2 patients with complete response. Response assessments were based on the rules set by the Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Adding the 22 patients with responses between less than 30% tumor shrinkage and less than 20% tumor increase, the disease control rate was 76%.
“Sacituzumab govitecan also produced significant duration of response in these responding patients. Measured as the time it takes from the beginning of sacituzumab govitecan treatments to when the cancer progresses, the median progression-free survival (PFS) for the 48 patients who received the optimal doses of 8 or 10 mg/kg was 6.0 months. Importantly, 63% of patients (22 of 35) had a time-to-progression longer than their last therapy, notwithstanding disease progression has not yet happened in 56% of patients at the time of analysis.
“These results were presented at the 2015 Annual Meeting of the American Society of Clinical Oncology by Dr. Aditya Bardia of Massachusetts General Hospital Cancer Center in Boston, MA, and a faculty member at Harvard Medical School, who commented, ‘Given that a majority of the patients enrolled into this study had failed 4 or more prior cancer therapies, some as many as 11, we are quite encouraged with sacituzumab govitecan in this late-stage setting in an aggressive disease that is difficult to treat.’ “
“Exelixis, Inc. EXEL, +9.21% today announced positive results from a phase 2 clinical study evaluating cabozantinib as a treatment for EGFR wild-type non-small cell lung cancer (NSCLC). The trial, Study E1512, is a randomized phase 2 trial by the ECOG-ACRIN Cancer Research Group of cabozantinib and erlotinib, alone or in combination, as second- or third-line therapy in patients with metastatic EGFR wild-type NSCLC. Exelixis previously announced positive top-line results from this trial in November 2014. Data from the trial will be presented today during an oral presentation (Abstract #8003) at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO), which is being held this week in Chicago, Illinois. Study chair Joel Neal, M.D., Ph.D., of ECOG-ACRIN’s Thoracic Cancer Committee and an Assistant Professor of Medicine (Oncology) at Stanford University/Stanford Cancer Institute will present the results.
“Study E1512 met its primary endpoint, demonstrating significant increases in progression-free survival (PFS) for cabozantinib and the combination of cabozantinib plus erlotinib when individually compared to the erlotinib arm. The median PFS for the combination of cabozantinib and erlotinib was 4.7 months versus 1.9 months for erlotinib alone, a more than two-fold increase that corresponds to a 65% reduction in the risk of disease worsening (hazard ratio [HR]=0.35, 80% CI 0.23-0.52, p=0.0005). The median PFS for cabozantinib monotherapy was 4.2 months versus 1.9 months for erlotinib alone, a more than doubling that corresponds to a 62% reduction in the risk of disease worsening (HR=0.38, 80% CI 0.27-0.55, p=0.0004).”