“Researchers found that in patients with non–small-cell lung cancer (NSCLC) and a Tumor Proportion Score (TPS) ≥ 50, pembrolizumab plus chemotherapy failed to improve overall survival (OS) or progression-free survival (PFS) compared with pembrolizumab alone.
“Results from the study were presented in a poster presentation at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer, held September 23–26 in Toronto.”
“A phase I trial found promising activity and good tolerability with the combination of pembrolizumab and a stimulant of Toll-like receptor 9 (TLR9) known as SD-101 in patients with unresectable or metastatic melanoma, particularly in those who had not received prior anti–programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy.
“PD-1/PD-L1 inhibition has improved outcomes in metastatic melanoma, and studies have indicated that combination therapy can increase immune responses further. “Despite the improvement in response rates with combination immunotherapy, a large unmet need remains,” wrote study authors led by Antoni Ribas, MD, PhD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center.”
“The use of steroids at baseline was associated with inferior survival outcomes in patients with advanced non-small cell lung cancer who were starting either PD-1 or PD-L1 blockade therapy, according to retrospective data presented at ASCO Annual Meeting.
” ‘Treatment with PD-1 and PD-L1 inhibitors is now standard therapy for nearly all patients with advanced non-small cell lung cancer,’ Kathryn C. Arbour, MD, a fellow at Memorial Sloan Kettering Cancer Center, said during her presentation. ‘The potential impact of steroids in patients with PD-1 or PD-L1 blockade has been an open question. Steroids are frequently used as a supportive medication in cancer care and can provide rapid relief of numerous cancer-related symptoms, including dyspnea, anorexia, pain, fatigue and symptoms associated with brain metastases. However … [physicians] routinely recognize that there can be substantial toxicities associated with long-term steroid use.’ ”
“Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab (Keytruda) had a greater median survival than patients treated with standard chemotherapy, even if the former had low levels of PD-L1, researchers reported here.
“Depending on the percentage of PD-L1 expression in the tumor, survival was between 4 and 8 months longer for patients treated with immunotherapy alone versus those treated with chemotherapy, according to Gilberto Lopes, MD, MBA, of the Sylvester Comprehensive Cancer Center at the University of Miami, and colleagues.”
“Immunotherapies targeting PD-1 and PD-L1 have become standards-of-care across all lines of therapy for patients with metastatic non-small cell lung cancer (NSCLC) who do not have targetable driver mutations. Furthermore, the PD-L1 inhibitor durvalumab was recently approved as consolidation therapy after chemoradiation in locally advanced NSCLC. Based on the improved outcomes seen with these agents in advanced NSCLC, they are now being evaluated in early stage NSCLC where effective therapies are needed, as many patients (particularly those beyond stage IB) relapse after surgery, despite neoadjuvant/adjuvant chemotherapy.”
Immune checkpoint inhibitor drugs that target the proteins PD-1 and PD-L1 are by now well established in the treatment of non-small cell lung cancer (NSCLC). In 2015, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo), an anti-PD-1 drug, for treatment of patients with metastatic NSCLC who progressed or relapsed after platinum-based chemotherapy. Atezolizumab (Tecentriq), an anti-PD-L1 drug, was approved in 2016 for treatment of NSCLC patients in the same situation. In October 2016, the FDA approved Pembrolizumab (Keytruda), a competing anti-PD-1 antibody, as first-line treatment in metastatic NSCLC patients whose tumors have high expression levels of the PD-L1 protein.
With these approvals, the stage was set to move these drugs into combination treatments that may increase their efficacy. Not surprisingly, combinations with chemotherapy have now been explored, among other possibilities. Continue reading…
“Adding atezolizumab (Tecentriq) to chemotherapy and an angiogenesis inhibitor led to significant improvement in progression-free survival (PFS) for patients with untreated advanced nonsquamous non–small cell lung cancer (NSCLC), according to results from an ongoing trial presented at the 2018 AACR Annual Meeting.
“In the IMpower150 trial, patients who received the PD-L1 inhibitor along with bevacizumab (Avastin) and chemotherapy had a median PFS of 8.3 months compared with 6.8 months with bevacizumab and chemotherapy. The difference translated into a 38% reduction in the hazard for progression or death (HR, 0.62; 95% CI, 0.52-0.74; P <.0001).”
Drugs that activate the immune system to attack cancer in a process known as immune checkpoint blockade (ICB) are a focus of intense investigation. A number of them are already approved by the U.S. Food and Drug Administration (FDA) for various cancers; namely, the anti-CTLA4 antibody ipilimumab (Yervoy), two anti-PD-1 antibodies: pembrolizumab (Keytruda) and nivolumab (Opdivo), and three anti-PD-L1 drugs: atezolizumab (Tecentriq), avelumab (Bavencio) and durvalumab (Imfinzi). These ICB drugs have the potential to induce durable cancer regressions, but the majority of cancer patients just do not respond to them at all.
Biomarkers, signature molecules in the blood or other tissue, can sometimes be used to predict a patient’s response to a given treatment. But no reliable biomarkers exist for ICB, and this is a serious concern. Patients who may really benefit from ICB could be overlooked, and patients who are not likely to respond may receive useless (and very expensive) ICB treatment.
Most potential response predictors that have already been identified are not yet useful for one or all of the following reasons: they are not extensively validated, their significance is still uncertain and may differ from one cancer (or even one patient) to another, or they are technically challenging for routine use. These markers are addressed below. Continue reading…
“Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the pivotal Phase 3 KEYNOTE-042 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC, including nonsquamous or squamous histologies) met its primary endpoint of overall survival (OS). An interim analysis conducted by the independent Data Monitoring Committee (DMC) demonstrated that treatment with KEYTRUDA resulted in significantly longer OS than platinum-based chemotherapy (carboplatin plus paclitaxel or carboplatin plus pemetrexed) in patients with a PD-L1 tumor proportion score (TPS) of ≥1 percent. As part of a pre-specified analysis plan, OS was sequentially tested and was significantly improved in patients with a TPS of ≥50 percent, with a TPS of ≥20 percent and then in the entire study population with a TPS of ≥1 percent. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported monotherapy studies involving patients with advanced NSCLC.”