The Journal of Community and Supportive Oncology

Drug therapy of chronic myeloid leukemia (CML) used to be simple. Or rather, it was narrow and not very effective. For a long time all we had was interferon alpha (IFN-alpha) and hydoxyurea, which failed to protect most patients from progression to the blastic phase. As a result, allotransplant, although associated with high mortality, was the treatment of choice for all eligible patients. Then imatinib came along and replaced a simple but poor choice with a simple but good choice for drug therapy. Now, 12 years later, the drug therapy space for CML is populated by 5 different tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) and omacetaxine (previously known as homoharringtonine) in addition to IFN-alpha and hydoxyurea. Navigating this space is a challenge, especially for hematologists and oncologists who don’t have the privilege of specializing. The drug at issue is bosutinib, which has been approved for treating adults “with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph) CML with resistance or intolerance to prior therapy,” but it has not received approval for frontline therapy. A combined phase 1/2 study demonstrated a 41% cumulative rate of complete cytogenetic response (CCyR) in patients with chronic phase CML with resistance to or intolerance of imatinib who were treated with bosutinib; progressionfree and overall survival at 2 years were 79% and 92%, respectively, with better results for patients with intolerance compared with patients with resistance. The results are quite comparable with those of nilotinib or dasatinib in the same setting.1-3 In contrast, only 24% of patients on bosutinib achieved CCyR if they had prior exposure to dasatinib or nilotinib in addition to imatinib, which is also similar to the results with dasatinib or nilotinib in the third line,4 although follow-up is shorter. Only 2 BCRABL1 kinase mutations confer resistance to bosutinib: the multiresistant T315I mutations and V299L.5

Drug therapy of chronic myeloid leukemia (CML) used to be simple. Or rather, it was narrow and not very effective. For a long time all we had was interferon alpha (IFN-alpha) and hydoxyurea, which failed to protect most patients from progression to the blastic phase. As a result, allotransplant, although associated with high mortality, was the treatment of choice for all eligible patients. Then imatinib came along and replaced a simple but poor choice with a simple but good choice for drug therapy. Now, 12 years later, the drug therapy space for CML is populated by 5 different tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) and omacetaxine (previously known as homoharringtonine) in addition to IFN-alpha and hydoxyurea. Navigating this space is a challenge, especially for hematologists and oncologists who don’t have the privilege of specializing. The drug at issue is bosutinib, which has been approved for treating adults “with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph) CML with resistance or intolerance to prior therapy,” but it has not received approval for frontline therapy. A combined phase 1/2 study demonstrated a 41% cumulative rate of complete cytogenetic response (CCyR) in patients with chronic phase CML with resistance to or intolerance of imatinib who were treated with bosutinib; progressionfree and overall survival at 2 years were 79% and 92%, respectively, with better results for patients with intolerance compared with patients with resistance. The results are quite comparable with those of nilotinib or dasatinib in the same setting.1-3 In contrast, only 24% of patients on bosutinib achieved CCyR if they had prior exposure to dasatinib or nilotinib in addition to imatinib, which is also similar to the results with dasatinib or nilotinib in the third line,4 although follow-up is shorter. Only 2 BCRABL1 kinase mutations confer resistance to bosutinib: the multiresistant T315I mutations and V299L.5

Drug therapy of chronic myeloid leukemia (CML) used to be simple. Or rather, it was narrow and not very effective. For a long time all we had was interferon alpha (IFN-alpha) and hydoxyurea, which failed to protect most patients from progression to the blastic phase. As a result, allotransplant, although associated with high mortality, was the treatment of choice for all eligible patients. Then imatinib came along and replaced a simple but poor choice with a simple but good choice for drug therapy. Now, 12 years later, the drug therapy space for CML is populated by 5 different tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) and omacetaxine (previously known as homoharringtonine) in addition to IFN-alpha and hydoxyurea. Navigating this space is a challenge, especially for hematologists and oncologists who don’t have the privilege of specializing. The drug at issue is bosutinib, which has been approved for treating adults “with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph) CML with resistance or intolerance to prior therapy,” but it has not received approval for frontline therapy. A combined phase 1/2 study demonstrated a 41% cumulative rate of complete cytogenetic response (CCyR) in patients with chronic phase CML with resistance to or intolerance of imatinib who were treated with bosutinib; progressionfree and overall survival at 2 years were 79% and 92%, respectively, with better results for patients with intolerance compared with patients with resistance. The results are quite comparable with those of nilotinib or dasatinib in the same setting.1-3 In contrast, only 24% of patients on bosutinib achieved CCyR if they had prior exposure to dasatinib or nilotinib in addition to imatinib, which is also similar to the results with dasatinib or nilotinib in the third line,4 although follow-up is shorter. Only 2 BCRABL1 kinase mutations confer resistance to bosutinib: the multiresistant T315I mutations and V299L.5

I have just returned from the Oncology Practice Summit, the annual conference for practice-based oncologists and midlevels, which was hosted by COMMUNITY ONCOLOGY and its sister publications, THE JOURNAL OF SUPPORTIVE ONCOLOGY (JSO) and THE ONCOLOGY REPORT, in Las Vegas. During my flight to the conference, I noticed that there was a certain buzz among the passengers, which I naturally assumed was about our oncology meeting. But as I looked around, I realized that not only was I the only passenger who was wearing a tie, I was also the only one who had knocked back less than one drink. The frenzy was about the first weekend of the NCAA’s March Madness, and the pervasive enthusiasm among the passengers revolved around the wellknown “science” of bracketology, in which basketball enthusiasts take all 64 teams in the tournament and try to predict which team will win each match as the teams work their way down to the Final Four and ultimately, to the winner. President Obama had already said that his pick was Indiana (we know now how that turned out — sorry Indiana), but the amateur handicappers on the plane were still sifting through the teams’ records and the coaches’ and individual players’ strengths and weakness to bet (upon their arrival in Las Vegas) on which team would ultimately prevail. Once in Las Vegas, we managed to have our conference despite the March Madness mayhem, and in the course of the meeting, the term bracketology took on an oncology-tinged relevance for me. Bear with me.

I have just returned from the Oncology Practice Summit, the annual conference for practice-based oncologists and midlevels, which was hosted by COMMUNITY ONCOLOGY and its sister publications, THE JOURNAL OF SUPPORTIVE ONCOLOGY (JSO) and THE ONCOLOGY REPORT, in Las Vegas. During my flight to the conference, I noticed that there was a certain buzz among the passengers, which I naturally assumed was about our oncology meeting. But as I looked around, I realized that not only was I the only passenger who was wearing a tie, I was also the only one who had knocked back less than one drink. The frenzy was about the first weekend of the NCAA’s March Madness, and the pervasive enthusiasm among the passengers revolved around the wellknown “science” of bracketology, in which basketball enthusiasts take all 64 teams in the tournament and try to predict which team will win each match as the teams work their way down to the Final Four and ultimately, to the winner. President Obama had already said that his pick was Indiana (we know now how that turned out — sorry Indiana), but the amateur handicappers on the plane were still sifting through the teams’ records and the coaches’ and individual players’ strengths and weakness to bet (upon their arrival in Las Vegas) on which team would ultimately prevail. Once in Las Vegas, we managed to have our conference despite the March Madness mayhem, and in the course of the meeting, the term bracketology took on an oncology-tinged relevance for me. Bear with me.

I have just returned from the Oncology Practice Summit, the annual conference for practice-based oncologists and midlevels, which was hosted by COMMUNITY ONCOLOGY and its sister publications, THE JOURNAL OF SUPPORTIVE ONCOLOGY (JSO) and THE ONCOLOGY REPORT, in Las Vegas. During my flight to the conference, I noticed that there was a certain buzz among the passengers, which I naturally assumed was about our oncology meeting. But as I looked around, I realized that not only was I the only passenger who was wearing a tie, I was also the only one who had knocked back less than one drink. The frenzy was about the first weekend of the NCAA’s March Madness, and the pervasive enthusiasm among the passengers revolved around the wellknown “science” of bracketology, in which basketball enthusiasts take all 64 teams in the tournament and try to predict which team will win each match as the teams work their way down to the Final Four and ultimately, to the winner. President Obama had already said that his pick was Indiana (we know now how that turned out — sorry Indiana), but the amateur handicappers on the plane were still sifting through the teams’ records and the coaches’ and individual players’ strengths and weakness to bet (upon their arrival in Las Vegas) on which team would ultimately prevail. Once in Las Vegas, we managed to have our conference despite the March Madness mayhem, and in the course of the meeting, the term bracketology took on an oncology-tinged relevance for me. Bear with me.

Lung cancer is the leading cause of cancer-related mortality among men and women in the United States. Non–small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Most patients with NSCLC present with advanced disease and median overall survival in this incurable setting remain dismal. Accumulating evidence suggests that both histology and molecular signature have prognostic and predictive value for NSCLC. Recent advances in the molecular characterization of NSCLC tumors have made individualized treatment approaches feasible. Personalized chemotherapy and targeted biological therapy based on a tumor’s individual biologic and molecular profile can optimize efficacy while minimizing toxicity. Molecular testing for activating mutations in the epidermal growth factor receptor (EGFR) domain and EML4-ALK translocation are routinely used to guide therapeutic decisions. Several new treatments that irreversibly target EGFR family members are in development for patients with NSCLC. Novel EML4-ALK inhibitors such as LDK378 are promising agents with encouraging early efficacy data. KRAS mutations are the most common mutation in adenocarcinomas. Although no agents for this subset of NSCLC have been approved, there are several agents in clinical development, including selumetinib, an MEK inhibitor, that seem promising. A growing body of evidence suggests that NSCLC is subject to immune surveillance. Immunotherapeutic interventions, including vaccine therapy and antigen-independent immunomodulatory strategies, may improve outcomes in NSCLC. In this review, we summarize recent advances in non–small-cell lung cancer, with an emphasis on investigational strategies for individualized treatment.

*Click on the link to the left for a PDF of the full article.

Lung cancer is the leading cause of cancer-related mortality among men and women in the United States. Non–small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Most patients with NSCLC present with advanced disease and median overall survival in this incurable setting remain dismal. Accumulating evidence suggests that both histology and molecular signature have prognostic and predictive value for NSCLC. Recent advances in the molecular characterization of NSCLC tumors have made individualized treatment approaches feasible. Personalized chemotherapy and targeted biological therapy based on a tumor’s individual biologic and molecular profile can optimize efficacy while minimizing toxicity. Molecular testing for activating mutations in the epidermal growth factor receptor (EGFR) domain and EML4-ALK translocation are routinely used to guide therapeutic decisions. Several new treatments that irreversibly target EGFR family members are in development for patients with NSCLC. Novel EML4-ALK inhibitors such as LDK378 are promising agents with encouraging early efficacy data. KRAS mutations are the most common mutation in adenocarcinomas. Although no agents for this subset of NSCLC have been approved, there are several agents in clinical development, including selumetinib, an MEK inhibitor, that seem promising. A growing body of evidence suggests that NSCLC is subject to immune surveillance. Immunotherapeutic interventions, including vaccine therapy and antigen-independent immunomodulatory strategies, may improve outcomes in NSCLC. In this review, we summarize recent advances in non–small-cell lung cancer, with an emphasis on investigational strategies for individualized treatment.

*Click on the link to the left for a PDF of the full article.

Lung cancer is the leading cause of cancer-related mortality among men and women in the United States. Non–small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Most patients with NSCLC present with advanced disease and median overall survival in this incurable setting remain dismal. Accumulating evidence suggests that both histology and molecular signature have prognostic and predictive value for NSCLC. Recent advances in the molecular characterization of NSCLC tumors have made individualized treatment approaches feasible. Personalized chemotherapy and targeted biological therapy based on a tumor’s individual biologic and molecular profile can optimize efficacy while minimizing toxicity. Molecular testing for activating mutations in the epidermal growth factor receptor (EGFR) domain and EML4-ALK translocation are routinely used to guide therapeutic decisions. Several new treatments that irreversibly target EGFR family members are in development for patients with NSCLC. Novel EML4-ALK inhibitors such as LDK378 are promising agents with encouraging early efficacy data. KRAS mutations are the most common mutation in adenocarcinomas. Although no agents for this subset of NSCLC have been approved, there are several agents in clinical development, including selumetinib, an MEK inhibitor, that seem promising. A growing body of evidence suggests that NSCLC is subject to immune surveillance. Immunotherapeutic interventions, including vaccine therapy and antigen-independent immunomodulatory strategies, may improve outcomes in NSCLC. In this review, we summarize recent advances in non–small-cell lung cancer, with an emphasis on investigational strategies for individualized treatment.

*Click on the link to the left for a PDF of the full article.

For the past 2 weeks I have been on call overnight and to put it lightly, it has been brutal. Fellow call, unlike resident call, can be taken from home, but some nights it seems almost as though it would be easier to just stay at the hospital. My pager typically starts going off at 5:01 pm and does not stop until sometime after midnight. Nightly, I have been averaging a record number of admissions, consults, outpatient calls, and enough inpatient issues to keep me awake stalking labs and vitals until the early morning, just in time to get the critical lab calls from nursing.

*Click on the link to the left of this introduction for a PDF of the full article.

For the past 2 weeks I have been on call overnight and to put it lightly, it has been brutal. Fellow call, unlike resident call, can be taken from home, but some nights it seems almost as though it would be easier to just stay at the hospital. My pager typically starts going off at 5:01 pm and does not stop until sometime after midnight. Nightly, I have been averaging a record number of admissions, consults, outpatient calls, and enough inpatient issues to keep me awake stalking labs and vitals until the early morning, just in time to get the critical lab calls from nursing.

*Click on the link to the left of this introduction for a PDF of the full article.

For the past 2 weeks I have been on call overnight and to put it lightly, it has been brutal. Fellow call, unlike resident call, can be taken from home, but some nights it seems almost as though it would be easier to just stay at the hospital. My pager typically starts going off at 5:01 pm and does not stop until sometime after midnight. Nightly, I have been averaging a record number of admissions, consults, outpatient calls, and enough inpatient issues to keep me awake stalking labs and vitals until the early morning, just in time to get the critical lab calls from nursing.

*Click on the link to the left of this introduction for a PDF of the full article.