“Jason J. Luke, MD, FACP, assistant professor of medicine, The University of Chicago, discusses the efficacy of PD-1/PD-L1 inhibitors in melanoma. The combination of these inhibitors, nivolumab and ipilimumab, was used to treat patients with previously untreated, unresectable or metastatic melanoma, in the Checkmate 069 study.
“Luke says PD-L1 is very complex and difficult when developing immunohistochemical assays. Since several pharmaceutical companies conduct different assays that test various things, a particular patient may be positive in one case, but not in another. For this reason, patients become very confused.
“Luke also mentions that there is no validated method across the board, so it is difficult to determine the next steps going forward.”
Of all cancer types, melanoma is the most investigated in terms of its potential to be treated through immune system-based approaches. More immunotherapy drugs are approved for melanoma than for any other type of cancer, and more are in development. Recent additions to the immunotherapy arsenal are the ‘anti-PD-1’ immune checkpoint blockade drugs pembrolizumab (Keytruda) and nivolumab (Opdivo). Continue reading…
“Rita Nanda, MD, assistant professor of Medicine, associate director, Breast Medical Oncology, The University of Chicago Medicine, discusses the efficacy of pembrolizumab and atezolizumab for the treatment of patients with metastatic triple-negative breast cancer (TNBC).
“Response rates seen with the two immunotherapy agents in two separate clinical trials in a heavily pretreated metastatic population was slightly under 20%, Nanda explains. This is significant due to how heavily pretreated these patients were, she adds.
“Furthermore, these responses were found to be durable and lasted up to 40 weeks. Both pembrolizumab and atezolizumab were shown to be well-tolerated. Patients experienced low-grade toxicities that were easily managed.”
The biggest news in melanoma treatment from the 2015 American Society of Clinical Oncology (ASCO) annual meeting was undoubtedly the report from a large, phase III, randomized clinical trial that compared a combination of two ‘checkpoint inhibitor’ drugs—nivolumab (Opdivo) and ipilimumab (Yervoy)—with the same drugs given alone.
In the CheckMate-067 trial, 945 previously untreated patients with unresectable stage III or IV melanoma were assigned to Opdivo alone, Opdivo plus Yervoy, or Yervoy alone. Continue reading…
“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.”
“Alexander Spira, MD, PhD, FACP, medical oncology, hematology, Virginia Cancer Specialists, discusses the POPLAR study for non-small cell lung cancer (NSCLC).
“The phase II study randomized patients with NSCLC to atezolizumab (MPDL3280A) or docetaxel in the second- or third-line setting. Patients who were administered the anti-PD-L1 agent were treated until practitioners determined there was no longer a benefit, Spira says. Patients in the docetaxel arm were treated until disease progression.
“At the interim analysis, which is not yet final, there was improved survival with atezolizumab. A correlation was also found between PD-L1 expression and efficacy of the drug. A phase III study is ongoing. Results from this study could also potentially identify a biomarker, Spira adds.”
“Drugmakers including Bristol-Myers Squibb Co and Merck & Co are testing which patients will most benefit from new cancer treatments based on a protein found in their tumors, but that guide, known as a biomarker, may be too unreliable, researchers and health experts said.
“Bristol’s Opdivo and Merck’s Keytruda are both therapies designed to block a protein known as Programmed Death receptor (PD-1) that tumors use to evade the body’s natural defenses. Competitors Roche Holding, AstraZeneca and Pfizer also have similar drugs in an earlier stage of development. The drugmakers are conducting clinical trials that test patient tumors for a related protein called PD-L1.
“The new drugs are mainly aimed at patients with so-called solid tumors suffering from diseases including lung cancer and liver cancer. Lung cancer, the most common type, claims 1.8 million new cases each year worldwide. Sales of drugs to block PD-1 could reach $33 billion a year by 2022, according to Morningstar.”
“Roche (SIX: RO, ROG; OTCQX: RHHBY) will present encouraging results from a Phase Ib study of the investigational cancer immunotherapy atezolizumab (MPDL3280A), in combination with a range of platinum-based chemotherapy combinations commonly used in the treatment of non-small cell lung cancer (NSCLC). The study showed that atezolizumab, a PD-L1 (programmed death ligand-1) inhibitor, shrank tumours (objective response rate; ORR) in 67 percent (20/30) of people with advanced NSCLC when combined with chemotherapy. The addition of atezolizumab to chemotherapy was well tolerated and no unexpected toxicities were reported. The most frequent adverse events (AEs) included those commonly associated with chemotherapy, such as nausea, fatigue and constipation. The data will be presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO).1
” ‘We are encouraged that a high proportion of people responded to combined treatment with atezolizumab (MPDL3280A) and chemotherapy in this early lung cancer study,’ said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. ‘This result indicates that combinations may provide a way to extend the benefits of atezolizumab to a wider range of people, including those with low levels of PD-L1 expression.’
“Roche currently has three ongoing Phase III studies of atezolizumab in combination with chemotherapy in previously untreated advanced NSCLC.”
“AstraZeneca AZN, -0.75% and MedImmune, AstraZeneca’s global biologics research and development arm, today presented encouraging results from their novel combination-focused immuno-oncology portfolio at the American Society of Clinical Oncology (ASCO) Annual Meeting 2015.
“Overall, data indicated clinical activity with manageable safety profiles for the anti-programmed cell death ligand 1 (PD-L1) monoclonal antibody MEDI4736, both as monotherapy and in combination with other immuno-oncology and small molecule therapies across different tumor types and tumor biology.
“MEDI4736 and tremelimumab combination shows clinical activity and tolerability in both PD-L1 positive and PD-L1 negative advanced non-small cell lung cancer (NSCLC) patients; dose confirmed for future studies
“Results from the combination study of MEDI4736 and tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) monoclonal antibody, in the treatment of advanced NSCLC, demonstrated clinical activity in heavily-pretreated patients with a manageable safety profile, establishing appropriate doses to move forward into Phase III combination trials.”