“Patients with a type of lung cancer called non-squamous non-small cell lung cancer (non-SQ NSCLC) have limited treatment options and a dismal prognosis once their disease has advanced and initial treatment with platinum-based chemotherapy has failed. Second-line treatment is usually with another chemotherapy drug, such as docetaxel or pemetrexed.
“Recent results have shown that the drug, nivolumab, improves survival for these patients and now updated results from the CheckMate 057 phase III clinical trial, to be reported at the 2015 European Cancer Congress today (Monday) with simultaneous publication of the study results in the New England Journal of Medicine, show that nivolumab continues to show an overall survival benefit compared to docetaxel. Among patients randomised to receive nivolumab, significantly more were alive at 12 months compared to those treated with docetaxel – 51% versus 39% respectively – and a difference in survival remains at 18 months – 39% for nivolumab versus 23% for docetaxel.
“This improvement in survival was observed for all patients included in the trial, but nivolumab was more effective in patients whose tumours expressed a protein called programmed death ligand 1 (PD-L1), which plays a role in the immune system’s ability to recognise and attack tumours and has been correlated with response to immune checkpoint inhibitors such as nivolumab.”
These days, it seems that I write mostly about immune checkpoint blockade drugs, or some other new immunotherapy treatment for cancer. This post is no different—it covers PD-L1, a protein that is at the center of clinical decisions for selecting patients who are likely to benefit from treatment with an anti-PD-1 or anti-PD-L1 drug. Continue reading…
“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that in the large pivotal Phase II study, BIRCH, the investigational cancer immunotherapy atezolizumab (MPDL3280A; anti-PDL1) met its primary endpoint and shrank tumours (objective response rate; ORR) in people with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease expressed PD-L1 (Programmed Death Ligand-1). The study showed the amount of PD-L1 expressed by a person’s cancer correlated with their response to the medicine. Adverse events were consistent with what has been previously observed for atezolizumab.
“ ‘We are encouraged by the number of people who responded to atezolizumab and maintained their response during the study, which is particularly meaningful for people who had received several prior treatments,’ said Sandra Horning, M.D., Chief Medical Officer and head of Global Product Development. ‘We plan to present results at an upcoming medical meeting and will discuss these data as well as results from our other lung cancer studies with health authorities to bring this medicine to patients as quickly as possible.’ “
“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.”