A Breast Cancer Tumor's Immune Signature Could Predict Response to Neoadjuvant Therapy

“In a study reported in the Journal of Clinical Oncology, Denkert et al found that increased tumor-infiltrating lymphocytes and the presence of lymphocyte-predominant breast cancer were associated with increased rates of pathologic complete response in patients receiving neoadjuvant anthracycline-taxane treatment with or without carboplatin. Higher rates were observed with carboplatin, with treatment interactions being significant among all patients and among those with HER2-positive disease but not among those with triple-negative disease. mRNA profiles for immune-related genes also distinguished pathologic complete response rates.

“The study involved 580 tumors from patients in the GeparSixto trial, which assessed the effects on pathologic complete response rates of adding carboplatin to neoadjuvant anthracycline plus taxane treatment. The current analysis assessed the effects on pathologic complete response of tumor-infiltrating lymphocyte levels, the presence of lymphocyte–predominant disease, and levels of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) and immunosuppressive genes (IDO1, PD-1, PD-L1, CTLA4, FOXP3).”


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.”


OncoGenex and Sarah Cannon Announce Completion of Patient Enrollment in the Spruce™ Clinical Trial Evaluating Apatorsen in Combination with Carboplatin and Pemetrexed in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer

“OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) and Sarah Cannon announced today that patient enrollment has been completed in the Spruce™ clinical trial, an investigator-sponsored, randomized, placebo-controlled Phase 2 trial evaluating apatorsen in combination with carboplatin and pemetrexed in patients with previously untreated, advanced, non-squamous, non-small cell lung cancer (NSCLC). Spruce is sponsored and led by Sarah Cannon Research Institute (SCRI), the research arm of Sarah Cannon, Hospital Corporation of America’s (HCA) global cancer enterprise, and is being conducted at 16 sites across the United States.

“In the Spruce trial, approximately 155 patients were randomized to receive either apatorsen or placebo in combination with carboplatin and pemetrexed therapy. The primary objective of the trial is progression-free survival (PFS), with additional analyses to evaluate overall survival, tumor response rates, safety, tolerability and the effect of therapy on heat shock protein 27 (Hsp27) levels.

” ‘Despite advances in targeted therapies to treat lung cancer, the majority of patients lack specific biomarkers and chemotherapy remains a mainstay of treatment for these patients,’ stated David Spigel MD, Director of the Lung Cancer Research Program at Sarah Cannon Research Institute and trial study chair. ‘The Spruce trial will enable us to better understand the role of apatorsen in treating NSCLC and its potential to delay or prevent treatment resistance and improve survival outcomes for these patients who urgently need more effective treatment options.’ “


Motesanib Fails in a Phase III Trial for NSCLC

The gist: New research results have dashed hopes that a drug called motesanib (AMG 706) might be an effective treatment for Asian people with stage IV, non-squamous non-small cell lung cancer (NSCLC). In 2011, the drug failed testing in patients, but data showed there might be some benefit for certain Asian patients. Testing continued in a group of patients from Japan, South Korea, Taiwan, and Hong Kong. However, the new results show that motesanib does not improve standard treatment with the drugs paclitaxel and carboplatin.


Adding Higher Dose Radiation or Cetuximab Doesn't Benefit Stage III NSCLC Patients Receiving Chemoradiation

The gist: An attempt to improve treatment for stage III non-small cell lung cancer (NSCLC) patients failed when it was tested in a clinical trial. People with stage III NSCLC are normally treated with radiation and chemotherapy. Researchers wondered if giving higher-dose radiation or adding the drug cetuximab (Erbitux) would improve the standard treatment. However, when tested in patients, neither approach worked better than the standard approach.

“As reported in The Lancet Oncology by Bradley and colleagues, the phase III Radiation Therapy Oncology Group 0617 trial showed no survival benefit of high- vs standard-dose radiotherapy or for addition of cetuximab (Erbitux) to concurrent paclitaxel-carboplatin chemoradiation in patients with inoperable stage IIIA or IIIB non–small cell lung cancer (NSCLC).

“In the open-label 2×2 factorial trial, patients from the United States and Canada were randomly assigned 1:1:1:1 between November 2007 and November 2011 to receive 60 Gy radiotherapy (n = 166), 74 Gy radiotherapy (n = 121), 60 Gy radiotherapy and cetuximab (n = 147), or 74 Gy radiotherapy and cetuximab (n = 110) with all patients receiving concurrent once-weekly chemotherapy with paclitaxel at 45 mg/m2 and carboplatin at area under the curve (AUC) 2. Two weeks after chemoradiation, patients received two cycles of consolidation paclitaxel at 200 mg/m2 and carboplatin at AUC 6 separated by 3 weeks. Radiation was given in 2-Gy daily fractions with either intensity-modulated or three-dimensional conformal radiation therapy. Cetuximab was given at 400 mg/m2 on day 1 followed by 250 mg/m2 weekly continued through consolidation therapy. The primary endpoint was overall survival.

“Patients had a median age of 64 years, and most were male (55%–64%), white (82%–89%), had Zubrod performance status of 0 (55%–59%), were current smokers (43%–51%), received three-dimensional conformal radiotherapy (47%–54%), underwent positron-emission tomography (PET) staging (89%–91%), had squamous histology (42%–47%), and had stage IIIA disease (63%–66%).”


Linifanib With Chemotherapy Delays Disease Worsening in Advanced Non-Squamous NSCLC

The gist: People with advanced non-squamous non-small cell lung cancer (NSCLC) might do better if a drug called linifanib is added to chemo treatment with the drugs carboplatin and paclitaxel. In a clinical trial with volunteer patients, people who took all three drugs went for several weeks longer without their disease worsening than patients who took only carboplatin and paclitaxel.

“The addition of linifanib to a carboplatin and paclitaxel regimen offered significantly improved progression-free survival (PFS) over placebo in a randomized phase II trial of patients with advanced non-squamous non–small-cell lung cancer (NSCLC).

“Previous work has shown that adding inhibitors of VEGF to standard chemotherapy can improve survival outcomes in advanced NSCLC. Linifanib (Abbott Laboratories) is a tyrosine kinase inhibitor with activity against VEGF and PDGF receptors. “Single-agent activity of linifanib in phase I and II clinical studies in patients with advanced NSCLC encouraged further evaluation of linifanib as a component of therapy for these patients,” wrote study authors led by Suresh S. Ramalingam, MD, of Winship Cancer Institute of Emory University in Atlanta…

“ ‘Although additional studies of linifanib in NSCLC are not currently planned, further evaluation of linifanib in patients with the identified biomarker signature is warranted,’ the authors concluded. ‘These findings are also of potential significance for other antiangiogenic agents presently under development for NSCLC.’ ”


Two Treatments Yield Similar Survival Rates in Stage III NSCLC

The gist: A recent study showed similar survival rates for two different drug combinations for stage III non-small cell lung cancer (NSCLC). The study compared  EP (treatment with the drugs etoposide and cisplatin) with CP (carboplatin plus paclitaxel). Both drug combinations were given along with radiation therapy. The study showed that EP might cause worse side effects, but the researchers say that more research will be needed to determine whether either EP or CP is better for treating stage III NSCLC.

“An analysis of Veterans Health Administration patients showed that etoposide/cisplatin (EP) and carboplatin/paclitaxel (CP) yielded similar overall survival along with radiotherapy in patients with stage III non–small-cell lung cancer (NSCLC), but EP was associated with increased morbidity. Prospective studies are still needed to determine the optimal treatment in these patients.

“ ‘There is considerable concern that CP, although better tolerated than EP, may be inferior in terms of disease control,’ wrote study authors led by Rafael Santana-Davila, MD, of the University of Washington in Seattle. To better understand the differences between the regimens, researchers looked into outcomes of patients in the VA Central Cancer Registry.

“The study included a total of 1,842 patients treated with concurrent radiotherapy and either EP or CP between 2001 and 2010. EP was used in 27% of the full cohort…

“Though the similar survival and increased morbidity with EP suggest CP may be the preferred treatment, Santana-Davila said in an email that “the study is not able to provide a firm recommendation. It has many limitations, and although we tried to adjust for confounders with several techniques, it is still a retrospective study.”

“Those limitations include a lack of data on dose or duration of therapy, and there were treatment differences such as an increased rate of consolidation chemotherapy with CP patients. The reliance on coded administrative data to identify toxicities is also less reliable than methods used in clinical trials.

“ ‘The only way we could provide firm recommendations would be with a phase III randomized trial,’ Santana-Davila said. In the meantime, the authors concluded that these results may simply help guide treatment decisions in stage III NSCLC patients.”