Adding Atezolizumab to Chemotherapy Shows Promise in NSCLC

“The anti–PD-L1 agent atezolizumab (MPDL3280A) was recently investigated for safety and efficacy in combination with platinum-based doublet chemotherapy in treatment-naïve patients with advanced non–small cell lung cancer (NSCLC). Results from the phase Ib study were presented at the 2015 ASCO Annual Meeting.

“The multiple-arm study looked at MPDL3280A with a different chemotherapy backbone in each arm: carboplatin plus paclitaxel (Arm C; n = 8) carboplatin plus pemetrexed (Arm D; n = 14) or carboplatin plus nab-paclitaxel (Arm E; n = 15).

“Across all arms, the overall response rate (ORR) was 67% (48%-82%), with 60% ORR (19%-92%) in Arm C (3 partial responses [PRs]), 75% (45%-93%) in Arm D (9 PRs), and 62% (33%-83%) in Arm E (6 PRs, 2 complete responses).

“Regarding the safety profile, the researchers concluded that the combination regimens were well tolerated. The most frequent all-grade adverse events included those commonly associated with chemotherapy, such as nausea (Arms C and D, 50%; Arm E, 73%), fatigue (Arm C, 38%; Arm D, 36%; Arm E, 73%) and constipation (Arm C, 25%; Arm D, 71%; Arm E, 27%).

“OncLive spoke with Stephen Liu, MD, lead author on the study and assistant professor, Division of Hematology and Oncology, Georgetown University, to better understand the results and purpose of the uniquely designed trial, and how oncologists may need to rethink trial design when investigating similar novel agents.”


AstraZeneca Presents Positive Data on AZD9291 in First-Line EGFR Mutated Lung Cancer at ASCO 2015

“AstraZeneca today announced preliminary efficacy and safety data for AZD9291 in the first-line treatment of epidermal growth factor receptor mutation positive (EGFRm) advanced non-small cell lung cancer (NSCLC). Data showed that 81% (95% confidence interval (CI) 68% to 89%) of patients on a once daily dose of AZD9291 were progression free at 9 months; overall response rate was 73% (95% CI 60% to 84%). The longest duration of response was ongoing at 13.8 months at the time of data cutoff.1

“The data from the first-line expansion cohorts of the AURA Phase I study were presented at the annual meeting of the American Society of Clinical Oncology in Chicago. The first-line cohorts included 60 patients with EGFRm advanced NSCLC who received AZD9291 80mg or 160mg once daily. The data are not fully mature with an approximate 11 month median follow up in the 80mg cohort, and an approximate 8.5 month median follow up in the 160mg cohort. The most common adverse events in both cohorts included rash (grade 3:0% at 80mg)(grade 3:3% at 160mg) and diarrhea (grade 3:0% at 80mg)(grade 3:7% at 160mg).1

“ ‘These preliminary data demonstrate the potential of AZD9291 in treatment-naive advanced NSCLC patients with EGFR mutation. These promising results with AZD9291 will be studied further by the ongoing Phase III FLAURA trial2 in the first-line setting,’ said Professor Suresh S. Ramalingam, Chief of Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA, who presented the AURA first-line data and is lead principal investigator for the FLAURA study.”


Docetaxel Improves Survival for Men with Hormone-Naive Prostate Cancer

“The addition of docetaxel to standard therapy clinically and significantly improved survival for men with locally advanced or metastatic hormone-naive prostate cancer, according to findings from the STAMPEDE trial.

“However, the addition of zoledronic acid to standard therapy was not associated with improved survival, results showed.

“ ‘We hope our findings will encourage doctors to offer docetaxel to men newly diagnosed with metastatic prostate cancer, if they are healthy enough for chemotherapy,’ Nicholas David James, MD, PhD, director of the cancer research unit at the University of Warwick and consultant in clinical oncology at Queen Elizabeth Hospital in the United Kingdom, said in a press release. ‘Men with locally advanced, nonmetastatic prostate cancer may also consider docetaxel as part of upfront therapy, as it clearly delays relapse.

“ ‘It’s also clear that zoledronic acid does not benefit these patients and should not be offered as an upfront treatment for advanced prostate cancer,’ James said.”


Treatment with Fulvestrant Improved Survival Over Anastrozole in Untreated, Advanced, HR+ Breast Cancer

The gist: A clinical trial with volunteer patients found that a drug called fulvestrant outperformed the drug anastrozole for women with advanced, hormone receptor-positive breast cancer. None of the women had received any other treatment for their cancer. “Patients assigned fulvestrant survived a median of 54.1 months compared with 48.4 months for anastrozole.”

“Fulvestrant 500 mg significantly improved overall survival compared with anastrozole, among women with treatment-naive, advanced, hormone receptor-positive breast cancer, according to data from the phase II FIRST trial presented at the 2014 San Antonio Breast Cancer Symposium (SABCS).

“ ‘This is now the second randomized controlled trial where fulvestrant 500 mg has shown a time-to-progression and survival advantage over the control arm,” said study presenter John Robertson, MD, professor of surgery, University of Nottingham, Royal Derby Hospital, United Kingdom.

“The phase III CONFIRM study found fulvestrant 500 mg to have a survival advantage over anastrozole in the second-line setting.

“According to Robertson, fulvestrant was originally developed in a 250 mg dosage. However, early trials of fulvestrant 250 mg in the first and second line showed only equivalence to anastrozole and similarity to tamoxifen. However, when it was decided to double the dose, and the CONFIRM study showed a survival advantage for fulvestrant 500 mg, the researchers decided to also look at outcomes with the higher dose in the first-line setting.”