“Merck’s abstract $MRK on its big study of Keytruda (pembrolizumab) combined with chemo hit early at ESMO, attracting considerable attention for the impressive progression-free survival data the pharma giant posted as a frontline therapy for non-small cell lung cancer.
“The scoop: The median PFS hit 19 months for the combo arm compared to 8.9 months for chemo alone. The 18-month overall survival rate was 70% with pembro + chemo and 56% with chemo. That was an easy winner at the FDA and the new mark to beat in the hottest competition in drug development.”
“Adding the IDO inhibitor indoximod to pembrolizumab (Keytruda) led to an overall response rate (ORR) of 61% in patients with advanced melanoma, according to updated phase II data scheduled to be presented at the Third International Cancer Immunotherapy Conference in Frankfurt/Mainz, Germany.
“The updated data include a higher complete response (CR) rate of 20% compared with the 12% CR rate previously reported at the 2017 AACR Annual Meeting.1 The median progression-free survival (PFS) with the combination was 12.9 months, with a 1-year PFS rate of 56%.”
“Immunotherapy is a promising approach in the treatment of metastatic melanoma, an aggressive and deadly form of skin cancer; but for most patients, immunotherapy drugs so far have failed to live up to their promise and provide little or no benefit. In a phase 1b clinical trial with 21 patients, researchers tested the safety and efficacy of combining the immunotherapy drug pembrolizumab with an oncolytic virus called T-VEC. The results suggest that this combination treatment, which had a 62% response rate, may work better than using either therapy on its own. The study appears September 7 in the journal Cell.”
“Pembrolizumab (Keytruda) induced an overall response rate (ORR) of 33% in patients with extensive-stage small cell lung cancer (SCLC), according to findings from the open-label, phase Ib KEYNOTE-028 trial published in the Journal of Clinical Oncology.
“One patient (4.2%) experienced a complete response, 7 (29.2%) had partial responses, and 1 (4.2%) had stable disease for less than 6 months. Thirteen patients (54.2%) experienced disease progression as the best overall response.”
“The combination of the programmed death receptor 1 (PD-1) inhibitor nivolumab at a reduced dose (1 mg/kg) with the cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor ipilimumab at standard dose (3 mg/kg) for four doses followed by standard-dose nivolumab alone is a standard of care for patients with advanced, previously untreated melanoma. This is based on results from the phase III CheckMate-067 trial that confirmed combination therapy is significantly more effective than single-agent nivolumab or ipilimumab. However, improvement in efficacy is associated with increased treatment-related grade 3/4 adverse events and treatment discontinuation in nearly 40% of patients.”
“Improvements in OS, but not PFS, indicate that maintenance treatment with pembrolizumab may benefit a subset of patients with small cell lung cancer, and biomarkers are needed to identify individuals in whom pembrolizumab may be effective, according to findings presented at the ASCO Annual Meeting.
” ‘The standard of care for these patients – 4 to 6 cycles of platinum plus etoposide – has not changed in the United States in the last 30 years,’ Shirish Gadgeel, MD, of the Karmanos Cancer Institute in Detroit, said during a presentation. ‘Despite a high response rate with this therapy, overall outcomes for these patients are quite poor. There is a need to identify other agents that can provide benefit in these patients.’ ”
There are many hopes that combining immune checkpoint inhibitor drugs, or combining them with drugs of other types (immunotherapy, targeted therapy, or chemotherapy) is the future of treatment for many kinds of cancer. Literally hundreds of clinical trials are actively exploring these combinations, and melanoma is the cancer for which trials of this type abound. Last month, the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago featured just a few presentations in this area, apparently because it is too early to report results from the many ongoing trials with drug combinations. Continue reading…
“In patients with heavily pretreated metastatic triple-negative breast cancer (TNBC), pembrolizumab (Keytruda) showed durable antitumor activity, according to findings from cohort A of the phase II KEYNOTE-086 trial presented at the 2017 ASCO Annual Meeting.
“The overall response rate (ORR) was 4.7% (95% CI, 2.3-9.2) with single-agent pembrolizumab, including a complete response (CR) rate of 0.6% and a partial response (PR) rate of 4.1%. The stable disease (SD) rate was 20.6%. The median duration of response was 6.3 months (range, 1.2+ to 10.3+).”
“At the 2017 ASCO Annual Meeting, results were presented from the phase II I-SPY 2 trial investigating pembrolizumab (Keytruda) in combination with standard therapy (paclitaxel followed by doxorubicin and cyclophosphamide) as a neoadjuvant treatment for patients with locally advanced triple-negative breast cancer or hormone receptor–positive/HER2-negative breast cancer (Abstract 506).
“Findings showed that the addition of pembrolizumab increased the estimated pathologic complete response rate nearly threefold in patients with triple-negative breast cancer (60% vs 20%) and in patients with hormone receptor–positive/HER2-negative breast cancer (34% vs 13%) compared to standard therapy. Overall, based on Bayesian predictive probability of success in a confirmatory phase III trial, pembrolizumab has graduated from the I-SPY 2 TRIAL for all signatures in which it was tested (triple-negative breast cancer, all HER2-negative, and hormone receptor–positive/HER2-negative).”