Report Prepared Matt Stenger, MS

The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. Two recent phase 1 studies of anti-PD-1 antibodies indicate that these agents exhibit considerable antitumor activity alone or in combination with ipilimumab in patients with advanced melanoma.

*Click on the links to the left for PDFs of the full article and related Commentary.

The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. Two recent phase 1 studies of anti-PD-1 antibodies indicate that these agents exhibit considerable antitumor activity alone or in combination with ipilimumab in patients with advanced melanoma.

*Click on the links to the left for PDFs of the full article and related Commentary.

The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. Two recent phase 1 studies of anti-PD-1 antibodies indicate that these agents exhibit considerable antitumor activity alone or in combination with ipilimumab in patients with advanced melanoma.

*Click on the links to the left for PDFs of the full article and related Commentary.

Bruton’s tyrosine kinase (BTK) is a critical component of B-cell–receptor signaling that mediates interactions with the tumor microenvironment and promotes survival and proliferation of chronic lymphocytic leukemia (CLL) cells. Ibrutinib is a first-in-class oral covalent inhibitor of BTK designed for the treatment of B-cell cancers. In a phase 1b/2 study reported by Byrd and colleagues, ibrutinib treatment was found to produce high rates of durable responses in patients with relapsed or refractory CLL or small lymphocytic lymphoma.¹

 
*Click on the links to the left for PDFs of the full article and related Commentary.

Bruton’s tyrosine kinase (BTK) is a critical component of B-cell–receptor signaling that mediates interactions with the tumor microenvironment and promotes survival and proliferation of chronic lymphocytic leukemia (CLL) cells. Ibrutinib is a first-in-class oral covalent inhibitor of BTK designed for the treatment of B-cell cancers. In a phase 1b/2 study reported by Byrd and colleagues, ibrutinib treatment was found to produce high rates of durable responses in patients with relapsed or refractory CLL or small lymphocytic lymphoma.¹

 
*Click on the links to the left for PDFs of the full article and related Commentary.

Bruton’s tyrosine kinase (BTK) is a critical component of B-cell–receptor signaling that mediates interactions with the tumor microenvironment and promotes survival and proliferation of chronic lymphocytic leukemia (CLL) cells. Ibrutinib is a first-in-class oral covalent inhibitor of BTK designed for the treatment of B-cell cancers. In a phase 1b/2 study reported by Byrd and colleagues, ibrutinib treatment was found to produce high rates of durable responses in patients with relapsed or refractory CLL or small lymphocytic lymphoma.¹

 
*Click on the links to the left for PDFs of the full article and related Commentary.

Recent studies have documented the ability of chimeric antigen receptor-modified autologous T cells targeting the CD19 antigen on B cells to induce rapid and deep remissions in adult and pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL).^1,2

*Click on the links to the left for PDFs of the full article and related Commentary.
 

Recent studies have documented the ability of chimeric antigen receptor-modified autologous T cells targeting the CD19 antigen on B cells to induce rapid and deep remissions in adult and pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL).^1,2

*Click on the links to the left for PDFs of the full article and related Commentary.
 

Recent studies have documented the ability of chimeric antigen receptor-modified autologous T cells targeting the CD19 antigen on B cells to induce rapid and deep remissions in adult and pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL).^1,2

*Click on the links to the left for PDFs of the full article and related Commentary.
 

Enzalutamide is an androgen receptor-signaling inhibitor that is reported to differ from conventional antiandrogen agents in that it inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment; exhibits increased affinity for the androgen receptor; and induces tumor reduction, rather than slowing growth, in preclinical models. The recently reported AFFIRM study showed that enzalutamide treatment after chemotherapy significantly prolonged overall survival (OS), radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and time to skeletal-related events (SREs) in men with castration-resistant prostate cancer. This trial formed the basis for the recent approval of enzalutamide for the treatment of patients with metastatic castrationresistant prostate cancer who have previously received docetaxel.

*Click on the links to the left for PDFs of the full article and related Commentary.  

Enzalutamide is an androgen receptor-signaling inhibitor that is reported to differ from conventional antiandrogen agents in that it inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment; exhibits increased affinity for the androgen receptor; and induces tumor reduction, rather than slowing growth, in preclinical models. The recently reported AFFIRM study showed that enzalutamide treatment after chemotherapy significantly prolonged overall survival (OS), radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and time to skeletal-related events (SREs) in men with castration-resistant prostate cancer. This trial formed the basis for the recent approval of enzalutamide for the treatment of patients with metastatic castrationresistant prostate cancer who have previously received docetaxel.

*Click on the links to the left for PDFs of the full article and related Commentary.  

Enzalutamide is an androgen receptor-signaling inhibitor that is reported to differ from conventional antiandrogen agents in that it inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment; exhibits increased affinity for the androgen receptor; and induces tumor reduction, rather than slowing growth, in preclinical models. The recently reported AFFIRM study showed that enzalutamide treatment after chemotherapy significantly prolonged overall survival (OS), radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and time to skeletal-related events (SREs) in men with castration-resistant prostate cancer. This trial formed the basis for the recent approval of enzalutamide for the treatment of patients with metastatic castrationresistant prostate cancer who have previously received docetaxel.

*Click on the links to the left for PDFs of the full article and related Commentary.  

Bosutinib was recently approved for the treatment of chronic phase (CP), accelerated phase (AP), or blast phase (BP) Philadelphia chromosomepositive (Ph+) chronic myeloid leukemia (CML) in adult patients with resistance or intolerance to prior therapy. The approval was based on findings in a combined phase 1/2 single-arm trial.1 The recently reported phase 3 BELA trial compared bosutinib and imatinib as first-line treatments in patients with CP CML and reported no difference in complete cytogenetic response (CCyR) rates at 1 year, but improved major molecular response (MMR) rate and time to response, as well as a distinct safety profile.2

*Click on the links to the left for PDFs of the full article and related Commentary.

Bosutinib was recently approved for the treatment of chronic phase (CP), accelerated phase (AP), or blast phase (BP) Philadelphia chromosomepositive (Ph+) chronic myeloid leukemia (CML) in adult patients with resistance or intolerance to prior therapy. The approval was based on findings in a combined phase 1/2 single-arm trial.1 The recently reported phase 3 BELA trial compared bosutinib and imatinib as first-line treatments in patients with CP CML and reported no difference in complete cytogenetic response (CCyR) rates at 1 year, but improved major molecular response (MMR) rate and time to response, as well as a distinct safety profile.2

*Click on the links to the left for PDFs of the full article and related Commentary.

Bosutinib was recently approved for the treatment of chronic phase (CP), accelerated phase (AP), or blast phase (BP) Philadelphia chromosomepositive (Ph+) chronic myeloid leukemia (CML) in adult patients with resistance or intolerance to prior therapy. The approval was based on findings in a combined phase 1/2 single-arm trial.1 The recently reported phase 3 BELA trial compared bosutinib and imatinib as first-line treatments in patients with CP CML and reported no difference in complete cytogenetic response (CCyR) rates at 1 year, but improved major molecular response (MMR) rate and time to response, as well as a distinct safety profile.2

*Click on the links to the left for PDFs of the full article and related Commentary.

Trastuzumab emtansine is an antibody drug conjugate composed of trastuzumab (T) linked to a highly potent cytotoxic derivative of maytansine (DM1) by a stable linker (a nonreducible thioether, SMCC).¹ DM1 binds to intracellular tubulin and prevents the assembly of microtubules, resulting in cell death. Trastuzumab targets the conjugate to the human epidermal growth factor receptor 2 (HER2) protein and the stable linker releases the cytotoxic agent only when the compound is internalized through receptor endocytosis. Trastuzumab emtansine (T-DM1) has been in found to be active in trastuzumab- and lapatinib-resistant disease, as well as in trastuzumab-naïve tumors...
 
*Click on the links to the left for PDFs of the full article and accompanying Commentary.

Trastuzumab emtansine is an antibody drug conjugate composed of trastuzumab (T) linked to a highly potent cytotoxic derivative of maytansine (DM1) by a stable linker (a nonreducible thioether, SMCC).¹ DM1 binds to intracellular tubulin and prevents the assembly of microtubules, resulting in cell death. Trastuzumab targets the conjugate to the human epidermal growth factor receptor 2 (HER2) protein and the stable linker releases the cytotoxic agent only when the compound is internalized through receptor endocytosis. Trastuzumab emtansine (T-DM1) has been in found to be active in trastuzumab- and lapatinib-resistant disease, as well as in trastuzumab-naïve tumors...
 
*Click on the links to the left for PDFs of the full article and accompanying Commentary.

Trastuzumab emtansine is an antibody drug conjugate composed of trastuzumab (T) linked to a highly potent cytotoxic derivative of maytansine (DM1) by a stable linker (a nonreducible thioether, SMCC).¹ DM1 binds to intracellular tubulin and prevents the assembly of microtubules, resulting in cell death. Trastuzumab targets the conjugate to the human epidermal growth factor receptor 2 (HER2) protein and the stable linker releases the cytotoxic agent only when the compound is internalized through receptor endocytosis. Trastuzumab emtansine (T-DM1) has been in found to be active in trastuzumab- and lapatinib-resistant disease, as well as in trastuzumab-naïve tumors...
 
*Click on the links to the left for PDFs of the full article and accompanying Commentary.

Vismodegib is an oral small-molecule inhibitor of smoothened homologue protein (SMO), a component of the hedgehog signaling pathway that has been shown to have activity in advanced basal cell carcinoma (BCC). In early 2012, vismodegib was approved by the Food and Drug Administration for treatment of adult patients with metastatic BCC (mBCC) who are not candidates for radiation therapy and adult patients with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy1…

*Click on the links to the left of this introduction for a PDF of the full article and an accompanying Commentary.

Vismodegib is an oral small-molecule inhibitor of smoothened homologue protein (SMO), a component of the hedgehog signaling pathway that has been shown to have activity in advanced basal cell carcinoma (BCC). In early 2012, vismodegib was approved by the Food and Drug Administration for treatment of adult patients with metastatic BCC (mBCC) who are not candidates for radiation therapy and adult patients with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy1…

*Click on the links to the left of this introduction for a PDF of the full article and an accompanying Commentary.

Vismodegib is an oral small-molecule inhibitor of smoothened homologue protein (SMO), a component of the hedgehog signaling pathway that has been shown to have activity in advanced basal cell carcinoma (BCC). In early 2012, vismodegib was approved by the Food and Drug Administration for treatment of adult patients with metastatic BCC (mBCC) who are not candidates for radiation therapy and adult patients with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy1…

*Click on the links to the left of this introduction for a PDF of the full article and an accompanying Commentary.

The multikinase inhibitor regorafenib was recently approved for the treatment of patients with metastatic colorectal cancer (mCRC) who had been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF therapy, and, for patients with wild-type KRAS tumors, anti-EGFR therapy.¹ Regorafenib inhibits numerous membrane-bound and intracellular kinases involved in normal cell function and in oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment (including RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR- , PDGFR- , FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl kinases). The approval was based on findings in the international, phase 3 CORRECT trial²…

*Click on the links to the left of this introduction for a PDF of the full article and related Commentary.  

The multikinase inhibitor regorafenib was recently approved for the treatment of patients with metastatic colorectal cancer (mCRC) who had been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF therapy, and, for patients with wild-type KRAS tumors, anti-EGFR therapy.¹ Regorafenib inhibits numerous membrane-bound and intracellular kinases involved in normal cell function and in oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment (including RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR- , PDGFR- , FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl kinases). The approval was based on findings in the international, phase 3 CORRECT trial²…

*Click on the links to the left of this introduction for a PDF of the full article and related Commentary.  

The multikinase inhibitor regorafenib was recently approved for the treatment of patients with metastatic colorectal cancer (mCRC) who had been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF therapy, and, for patients with wild-type KRAS tumors, anti-EGFR therapy.¹ Regorafenib inhibits numerous membrane-bound and intracellular kinases involved in normal cell function and in oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment (including RET, VEGFR1, VEGFR2, VEGFR3, KIT, PDGFR- , PDGFR- , FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl kinases). The approval was based on findings in the international, phase 3 CORRECT trial²…

*Click on the links to the left of this introduction for a PDF of the full article and related Commentary.  

In July 2012, cetuximab was approved for use in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment of patients with KRAS mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer (mCRC) as determined by Food and Drug Administration-approved tests. A companion diagnostic, Therascreen KRAS RGQ PCR Kit for determining KRAS mutation status was approved concurrently with the cetuximab approval. The test is a real-time polymerase chain reaction assay that detects 7 mutations of the KRAS gene; tumors with none of these mutations are considered wild-type KRAS tumors.

*For PDFs of the full article and accompanying Commentary, click on the links to the left of this introduction.

In July 2012, cetuximab was approved for use in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment of patients with KRAS mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer (mCRC) as determined by Food and Drug Administration-approved tests. A companion diagnostic, Therascreen KRAS RGQ PCR Kit for determining KRAS mutation status was approved concurrently with the cetuximab approval. The test is a real-time polymerase chain reaction assay that detects 7 mutations of the KRAS gene; tumors with none of these mutations are considered wild-type KRAS tumors.

*For PDFs of the full article and accompanying Commentary, click on the links to the left of this introduction.

In July 2012, cetuximab was approved for use in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment of patients with KRAS mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer (mCRC) as determined by Food and Drug Administration-approved tests. A companion diagnostic, Therascreen KRAS RGQ PCR Kit for determining KRAS mutation status was approved concurrently with the cetuximab approval. The test is a real-time polymerase chain reaction assay that detects 7 mutations of the KRAS gene; tumors with none of these mutations are considered wild-type KRAS tumors.

*For PDFs of the full article and accompanying Commentary, click on the links to the left of this introduction.

In July 2012, carfilzomib was given accelerated approval by the Food and Drug Administration for the treatment of patients with multiple myeloma (MM) who have received at least 2 prior therapies including bortezomib and an immunomodulatory agent and have exhibited disease progression during or within 60 days of completing their last therapy. The approval was based on results of a single-arm, multicenter phase 2 trial of carfilzomib in patients with relapsed and refractory MM. As a condition of the accelerated approval, the manufacturer of the drug has to submit a final analysis of an ongoing phase 3 trial that compares carfilzomib plus lenalidomide plus low-dose dexamethasone with lenalidomide plus low-dose dexamethasone in patients with relapsed and refractory MM after 1 to 3 previous therapies. The primary end point of this trial is progression-free survival (PFS)...

*For a PDF of the full article and accompanying Commentaries, click on the links to the left of this introduction.

In July 2012, carfilzomib was given accelerated approval by the Food and Drug Administration for the treatment of patients with multiple myeloma (MM) who have received at least 2 prior therapies including bortezomib and an immunomodulatory agent and have exhibited disease progression during or within 60 days of completing their last therapy. The approval was based on results of a single-arm, multicenter phase 2 trial of carfilzomib in patients with relapsed and refractory MM. As a condition of the accelerated approval, the manufacturer of the drug has to submit a final analysis of an ongoing phase 3 trial that compares carfilzomib plus lenalidomide plus low-dose dexamethasone with lenalidomide plus low-dose dexamethasone in patients with relapsed and refractory MM after 1 to 3 previous therapies. The primary end point of this trial is progression-free survival (PFS)...

*For a PDF of the full article and accompanying Commentaries, click on the links to the left of this introduction.

In July 2012, carfilzomib was given accelerated approval by the Food and Drug Administration for the treatment of patients with multiple myeloma (MM) who have received at least 2 prior therapies including bortezomib and an immunomodulatory agent and have exhibited disease progression during or within 60 days of completing their last therapy. The approval was based on results of a single-arm, multicenter phase 2 trial of carfilzomib in patients with relapsed and refractory MM. As a condition of the accelerated approval, the manufacturer of the drug has to submit a final analysis of an ongoing phase 3 trial that compares carfilzomib plus lenalidomide plus low-dose dexamethasone with lenalidomide plus low-dose dexamethasone in patients with relapsed and refractory MM after 1 to 3 previous therapies. The primary end point of this trial is progression-free survival (PFS)...

*For a PDF of the full article and accompanying Commentaries, click on the links to the left of this introduction.