Treatment for metastatic pancreatic cancer has seen progress in recent years, but outcomes remain poor and treatment advances that can prolong patients’ lives, even for a few months, are eagerly awaited. Two papers published today in the scientific journal Nature Medicine report that a new combination of two drugs that are FDA-approved for other conditions may significantly delay progression of pancreatic cancer in cells and in mice. Furthermore, the first patient treated with this combination experienced a prolonged response that lasted almost 6 months.
In light of these promising results, Cancer Commons is partnering with xCures to track the experiences of patients who choose to try this new combination therapy. Continue reading…
“Bristol-Myers Squibb Company (NYSE: BMY) today announced initial results from the pivotal Phase 3 study, CheckMate -227, evaluating the Opdivo (nivolumab) 3 mg/kg pluslow-dose Yervoy (ipilimumab, 1 mg/kg) combination in first-line advanced non-small cell lung cancer (NSCLC) patients with high tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb). In the study, the combination demonstrated a superior benefit for the co-primary endpoint of progression-free survival (PFS) versus chemotherapy (HR 0.58; 97.5% CI: 0.41 to 0.81; p=0.0002). The PFS benefit was observed regardless of PD-L1 expression levels and in both squamous and non-squamous tumor histology. Additionally, based on an early descriptive analysis, encouraging overall survival was observed with the combination versus chemotherapy in patients with high TMB ≥10 mut/Mb (HR 0.79; 95% CI: 0.56 to 1.10).”
“Patients with advanced or metastatic melanoma have been able to live longer cancer-free lives because of several new therapies approved over the last decade, such as BRAF and MEK inhibitors. However, despite the success of these targeted agents, most patients eventually develop drug resistance and their cancer regrows. A team of researchers at Moffitt Cancer Center have been working to learn more about how melanoma becomes resistant to BRAF inhibitors in order to develop new treatment strategies. They tested whether a drug targeting heat shock protein 90 (HSP90) combined with the BRAF inhibitor vemurafenib could be a safe and potentially effective strategy to treat patients with melanoma. Their study was published online ahead of print in Clinical Cancer Research.”
“As immunotherapies continue to make up a larger share of new cancer drugs, researchers are looking for the most effective ways to use these cutting edge treatments in combination with each or with other pre-existing options. New studies from the Abramson Cancer Center of the University of Pennsylvania are providing fresh clues on potentially effective combinations with CAR T therapy in brain cancer as well as a novel therapeutic target in head and neck cancer, and also providing greater understanding of the mechanisms of resistance in pancreatic cancer. All three studies will be presented as late breaking abstracts at the American Association for Cancer Research Annual Meeting in Chicago.”
“Although modern immunotherapy has yet to have a breakthrough in prostate cancer to the degree it has had in lung cancer or urothelial carcinoma, combinations with anti–PD-1/PD-L1 agents are beginning to show promise for these patients in clinical trials.
“Currently ongoing is a phase II trial of durvalumab (Imfinzi) in combination with the PARP inhibitor olaparib (Lynparza) in patients with metastatic castration-resistant prostate cancer (mCRPC; NCT02484404). Investigators note that previous data have suggested that 25% to 30% of sporadic mCRPC has DNA-repair pathway defects. Results thus far have demonstrated that the synergy of durvalumab and olaparib proves that the combination may be a viable option for patients with mCRPC who are heavily pretreated. The trial is still accruing.”
“Updated results of the phase Ib/II ENHANCE1/KEYNOTE-150 study presented at the 2017 San Antonio Breast Cancer Symposium found that the combination of pembrolizumab (Keytruda) and eribulin (Halaven) was associated with a 26.4% objective response rate (ORR) for patients with metastatic triple-negative breast cancer (TNBC).
“In the open-label study, the ORR with the combination for untreated patients with metastatic TNBC (n = 65) was 29.2% (95% CI, 18.6%-41.8%). In a cohort of patients pretreated with 1 to 2 therapies (n = 41), the ORR was 22.0% (95% CI, 10.6%-37.6%). Across all treatment arms, there were 3 complete responses to the combination (2.8%).”
“A new combination therapy for the first line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC) improves progression-free survival (PFS), according to results of the phase III IMpower150 trial presented at the ESMO Immuno Oncology Congress 2017.
” ‘This is the first phase III trial to report on the combination of chemotherapy, antiangiogenic treatment and immunotherapy as first line treatment for advanced non-squamous NSCLC,’ said lead author Professor Martin Reck, chief oncology physician, Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. ‘The trial met its co-primary endpoint of PFS and the preliminary results of the co-primary endpoint of overall survival (OS), although immature, look encouraging.’ ”
“Combination regimens—particularly with checkpoint inhibitors and chemotherapy—are showing promise for the treatment of patients with squamous non–small cell lung cancer (NSCLC).
“Beyond the May 2017 FDA approval of pembrolizumab (Keytruda) plus carboplatin/pemetrexed for nonsquamous patients regardless of PD-L1 status, researchers are turning their focus to immunotherapy combinations in squamous patients in ongoing clinical trials. For example, the randomized, open-label, phase III IMpower131 study is evaluating the safety and efficacy of atezolizumab (Tecentriq) in combination with carboplatin/paclitaxel or carboplatin/nab-paclitaxel (Abraxane) versus carboplatin/nab-paclitaxel in chemotherapy-naïve patients with stage IV squamous NSCLC (NCT02367794). The trial, which has a primary endpoint of progression-free survival, is expected to enroll 1021 patients.”
“Neoadjuvant treatment with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) demonstrated almost a tripling in objective response rate (ORR) compared with the PD-1 inhibitor alone but at the cost of significant added grade 3 adverse events (AEs) for patients with high-risk resectable melanoma, according to a small study presented at the 2017 SITC Annual Meeting.
“In the combination arm (n = 11), the ORR was 73% and 50% of patients achieved a pathological complete response (pCR). With nivolumab alone (n = 12), the ORR was 25% and the pCR rate was 25%. Unfortunately, these gains in response were accompanied by 73% of patients in the combination arm having a grade 3 AE compared with just 8% in the single-agent arm. This high level of toxicity led the researchers to close the study early, according to Sangeetha M. Reddy, MD, MSci. Reddy worked on this trial with co-investigators Rodabe Amaria, MD, and Jennifer Wargo, MD.”