Atezolizumab Plus Chemotherapy Improves PFS for Triple-Negative Breast Cancer

Excerpt:

“First-line atezolizumab plus nab-paclitaxel improved PFS compared with placebo among patients with metastatic or unresectable locally advanced triple-negative breast cancer, according to interim results from the IMpassion130 trial released by the manufacturer.

“Researchers observed prolonged PFS in both the intention-to-treat population and the PD-L1-positive population.”

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Atezolizumab Plus Carboplatin/Nab-Paclitaxel Improves OS in Frontline NSCLC

Excerpt:

“Adding atezolizumab (Tecentriq) to nab-paclitaxel (Abraxane) and carboplatin in the frontline setting significantly improved overall survival (OS) in patients with advanced non–small cell lung cancer (NSCLC), according to findings from the phase III IMpower130 study.

“Atezolizumab also improved progression-free survival (PFS), the coprimary endpoint of the IMpower130 study, according to Genentech (Roche), the manufacturer of the PD-L1 inhibitor. The company plans to share the study data at an upcoming oncology meeting.”

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Nab-Paclitaxel Shows Greatest Utility for TNBC

Excerpt:

“Treatment with nab-paclitaxel (Abraxane) showed promising improvements in overall survival (OS) and progression-free survival (PFS) compared with standard paclitaxel for patients with metastatic triple-negative breast cancer (TNBC), according to post-hoc findings from the CALGB 40502/NCCTG N063H trial presented at the 2017 San Antonio Breast Cancer Symposium (SABCS).

“For those with TNBC in the phase III trial (n = 201), the median OS with nab-paclitaxel was 21.0 months compared with 15.3 months with standard paclitaxel, representing a 26% reduction in the risk of death. Given the limitations of the post-hoc assessment, these findings were not powered for statistical significance, explained lead investigator Hope S. Rugo, MD. The hazard ratio for the comparison was 0.74 (95% CI, 0.51-1.07).”

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Expert Highlights Immunotherapy Progress in Squamous Cell Lung Cancer

Excerpt:

“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.”

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Nab-Paclitaxel Paired With Anti-PD-L1 Immunotherapies in TNBC Studies

Excerpt:

“Combination regimens that pair nab-paclitaxel (Abraxane) with PD-L1 checkpoint blockade immunotherapy agents are emerging as a robust area of investigation in triple-negative breast cancer (TNBC), bolstered by clinical trial results that establish the chemotherapeutic agent as an effective partner for other therapies.

“Although nab-paclitaxel has been combined in some studies with other chemotherapies, the focus is shifting to regimens that include immunotherapies as the efficacy of that approach continues to grow. Nab-paclitaxel, an albumin-bound form of paclitaxel, is indicated for patients with metastatic breast cancer after prior chemotherapy.”

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Putting Immune Checkpoint Blockade to the Test in Breast Cancer


About 10 months ago, we asked: Is There a Future for Immunotherapy in Breast Cancer? Now, we can answer this question with a qualified “yes.” The data show why:

Triple-negative breast cancer (TNBC)

TNBC has long been considered to be more amenable to immune system-based treatments than other types of breast cancer because it is more immunogenic; that is, relatively high levels of immune cells accumulate within or adjacent to TNBC tumors. These immune cells could be triggered to attack tumors if properly activated. TNBC tumors are also likely to have a higher mutational burden (number of genetic mutations). This is one of the predictors of sensitivity to a type of treatment called immune checkpoint blockade.  Drugs known as checkpoint inhibitors block the proteins PD-1 or PD-L1. In cancer, PD-L1 proteins on tumor cells bind to PD-1 proteins on immune T cells and inhibit their tumor-killing activity. Immune checkpoint drugs disable this interaction and enable activation of T cells. These drugs are actively being explored in TNBC in clinical trials.

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Atezolizumab/Nab-Paclitaxel Combo Shows High Response Rates in TNBC

“Upfront treatment with the PD-L1 inhibitor atezolizumab (MPDL3280A) plus nab-paclitaxel (Abraxane) showed a confirmed objective response rate (ORR) of 66.7% in patients with metastatic triple-negative breast cancer (TNBC), according to data presented at the 2015 San Antonio Breast Cancer Symposium.

“In the phase Ib study, atezolizumab plus nab-paclitaxel was explored across several lines of treatment regardless of PD-L1 status for patients with metastatic TNBC. In the second-line setting, the confirmed ORR was 25% and in the third-line and beyond the ORR was 28.6%. Across the full trial, the ORR was 41.7%.

“ ‘For the efficacy, we saw a very high response rate, which is extremely exciting and encouraging,’ said lead investigator Sylvia Adams, MD, associate professor of Medicine, NYU Perlmutter Cancer Center. ‘The combination was well-tolerated without additive toxicity. We saw only toxicity that was predictable for the single agents alone.’ “


ESMO Commentary: Preliminary Results from PERUSE Study Increase Treatment Options in HER-Positive Patients with Metastatic Breast Cancer

Preliminary safety results from the PERUSE study presented at the European Cancer Congress 2015 (ECC 2015) in Vienna, Austria, open the door for the taxanes nab-paclitaxel and paclitaxel to be used in HER2-positive patients with metastatic breast cancer.

“ ‘Therapy in HER2-positive metastatic breast cancer has been influenced by the CLEOPATRA trial, which led to the registration of pertuzumab and trastuzumab in the first line setting,’ said Professor Jens Huober, Head of the Breast Centre at the University of Ulm, Germany who has shared his views on new steps forward in the treatment of this subset of patients. ‘The CLEOPATRA trial used only docetaxel,’ he added.

“ ‘With PERUSE we now know that at least in terms of safety and tolerability we have good alternatives to docetaxel, namely nab-paclitaxel and paclitaxel, which for the majority of patients are probably less toxic,’ he said.”


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.”