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.”


ABRAXANE® Approved by European Commission for First-Line Treatment of Patients with Non-Small Cell Lung Cancer

“Celgene International Sàrl, a wholly owned subsidiary of Celgene Corporation CELG, -0.88% today announced that the European Commission (EC) has approved ABRAXANE® (paclitaxel formulated as albumin-bound nanoparticles, or nab-paclitaxel) in combination with carboplatin for the first-line treatment of non-small cell lung cancer in adult patients who are not candidates for potentially curative surgery and/or radiation therapy.

“The ABRAXANE Marketing Authorisation has been updated across 28 member states in the European Union to include this new indication in non-small cell lung cancer (NSCLC), adding to the existing indications for the treatment of metastatic pancreatic and breast cancers.

“Lung cancer is the fourth most commonly diagnosed cancer in both men and women, however it is the leading cause of cancer-related mortality in Europe. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for 85 to 90% of all cases. The predominant cause of lung cancer is cigarette smoking, although environmental and occupational factors also can cause the cancer.

“The EC decision follows the positive CHMP opinion received on 23 January and is based on the results of a multicenter, randomized, open-label study including 1,052 chemotherapy-naive patients with Stage IIIb/IV non-small cell lung cancer. The study compared ABRAXANE in combination with carboplatin versus solvent-based paclitaxel in combination with carboplatin as first-line treatment in patients with advanced non-small cell lung cancer. The primary efficacy endpoint, overall response rate, was significantly higher for patients in the ABRAXANE/carboplatin arm at 33%, compared with patients in the control arm, at 25%. The most common adverse reactions (greater-than or equal to 20%) of ABRAXANE in combination with carboplatin for NSCLC were anaemia, neutropenia, thrombocytopenia, peripheral neuropathy, nausea, and fatigue.”


FDA Names New Drug Tarextumab "Orphan Drug" for Small Cell Lung Cancer

The gist: The U.S. Food and Drug Administration (FDA) has granted “orphan drug” designation to a new drug called tarextumab for small cell lung cancer (SCLC) and pancreatic cancer. The designation will make it easier for the drug maker to successfully develop tarextumab and get it to patients in the U.S. Tarextumab has shown promise in patients in a clinical trial. It is given to patients in combination with chemotherapy.

“The US Food and Drug Administration (FDA) has granted orphan drug designation to the OncoMed agent tarextumab for the treatment of pancreatic cancer and lung cancer. Tarextumab (formerly OMP-59R5) is a fully human monoclonal antibody targeting the Notch 2/3 receptors.

“ ‘We are excited to receive two separate orphan drug designations for tarextumab for the treatment of pancreatic and small-cell lung cancer,’ said Paul J. Hastings, OncoMed’s chairman and chief executive officer, in a statement.

“Earlier this month the drug company announced final phase 1b clinical and biomarker data from the ALPINE (Antibody Therapy in First-Line Pancreatic Cancer Investigating Anti-Notch Efficacy and Safety) study, which tested tarextumab in combination with gemcitabine plus nab-paclitaxel in pancreatic cancer.

“Of the 29 patients in the trial, 21 (73%) achieved either a partial response or stable disease with the combination therapy.”


Phase III Results Demonstrate Significant Pathological Complete Response for Nab-Paclitaxel in Neoadjuvant Breast Cancer–

The gist: The drug nab-paclitaxel (aka Abraxane) has shown promise for patients with early-stage, high-risk breast cancer. Nab-paclitaxel is an injectable version of the chemotherapy drug paclitaxel. In a clinical trial, tumors disappeared in 38% of the patients who took nab-paclitaxel, compared to 29% of patients who took conventional paclitaxel. Learn more about the treatment, and its side effects, here.

“The German Breast Group (GBG) said nab-paclitaxel (ABRAXANE®) demonstrated significant benefit for patients with early high risk breast cancer when compared to conventional solvent-based paclitaxel. The findings are from the GeparSepto clinical trial sponsored by GBG and conducted together with the German AGO-B study group involving over 1200 patients, which is the largest randomized Phase III study ever completed with nab-paclitaxel and the first one completed in high risk early breast cancer. The results were presented by the coordinating investigator Michael Untch, M.D., Berlin in General Session 2 on December 10th, at the 2014 San Antonio Breast Cancer Symposium.

“The study found a statistically significant and clinically meaningful 9% absolute improvement from 29% to 38% (p=<0.001) in the pCR (pathological complete response) rate, when neoadjuvant (preoperative) chemotherapy was started with nab-paclitaxel instead of conventional solvent-based paclitaxel followed by epirubicin/cyclophosphamide given all before surgery. Pathological complete response after neoadjuvant treatment for breast cancer is a surrogate marker for long-term efficacy.

“ ‘The phase III study provided a head-to-head comparison of weekly nab-paclitaxel with weekly conventional paclitaxel followed by epirubicin/cyclophosphamide in both arms before surgery. Our findings clearly demonstrate nab-paclitaxel is superior to paclitaxel in achieving pCRs in early high risk breast cancer,’ Prof. Dr. Michael Untch.”


NICE 'No' for Celgene's Abraxane in Pancreatic Cancer

The National Institute for Health and Care Excellence has published new recommendations rejecting the use of Celgene’s Abraxane (nab-paclitaxel) on the National Health Service to treat patients with advanced pancreatic cancer.

“According to the cost regulator, the drug, a novel formulation of the chemotherapy paclitaxel, is not as effective as standard therapy and is more expensive, and thereby fails to hit value-for-money criteria.

“NICE says that data provided by Celgene show that the chemo regimen FOLFIRINOX, a first-line option for patients with the disease, was actually more clinically effective than the Abraxane/gemcitabine combination. And while Abraxane/gemcitabine was more effective than gemcitabine alone, it resulted in more serious side effects.”