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FDA fast-tracks CX-01 for newly diagnosed AML
The Food and Drug Administration has granted fast-track designation to CX-01 as a treatment for patients older than 60 years receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).
CX-01 also has orphan drug designation from the FDA.
CX-01 is a polysaccharide derived from heparin thought to enhance chemotherapy by disrupting leukemia cell adhesion in bone marrow. Cantex Pharmaceuticals is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.
This study builds upon results of a pilot study, which were published in Blood Advances (Blood Adv. 2018 Feb 27;2[4]:381-9). The pilot study enrolled 12 adults with newly diagnosed AML who received CX-01 as a continuous infusion for 7 days, along with standard induction chemotherapy (cytarabine and idarubicin).
A total of 11 patients achieved morphological complete remission after one cycle of induction. This included two patients who did not complete induction. All patients received subsequent therapy – consolidation, salvage, or transplant – on or off study.
At a median follow-up of 24 months, eight patients were still alive. Two patients died of transplant-related complications, one died of infectious complications, and one died of cerebral hemorrhage. The median disease-free survival was 14.8 months, and the median overall survival was not reached.
There were five serious adverse events in five patients; most were considered unrelated to CX-01, but a case of grade 4 sepsis was possibly related.
The FDA’s fast-track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
The Food and Drug Administration has granted fast-track designation to CX-01 as a treatment for patients older than 60 years receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).
CX-01 also has orphan drug designation from the FDA.
CX-01 is a polysaccharide derived from heparin thought to enhance chemotherapy by disrupting leukemia cell adhesion in bone marrow. Cantex Pharmaceuticals is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.
This study builds upon results of a pilot study, which were published in Blood Advances (Blood Adv. 2018 Feb 27;2[4]:381-9). The pilot study enrolled 12 adults with newly diagnosed AML who received CX-01 as a continuous infusion for 7 days, along with standard induction chemotherapy (cytarabine and idarubicin).
A total of 11 patients achieved morphological complete remission after one cycle of induction. This included two patients who did not complete induction. All patients received subsequent therapy – consolidation, salvage, or transplant – on or off study.
At a median follow-up of 24 months, eight patients were still alive. Two patients died of transplant-related complications, one died of infectious complications, and one died of cerebral hemorrhage. The median disease-free survival was 14.8 months, and the median overall survival was not reached.
There were five serious adverse events in five patients; most were considered unrelated to CX-01, but a case of grade 4 sepsis was possibly related.
The FDA’s fast-track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
The Food and Drug Administration has granted fast-track designation to CX-01 as a treatment for patients older than 60 years receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).
CX-01 also has orphan drug designation from the FDA.
CX-01 is a polysaccharide derived from heparin thought to enhance chemotherapy by disrupting leukemia cell adhesion in bone marrow. Cantex Pharmaceuticals is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.
This study builds upon results of a pilot study, which were published in Blood Advances (Blood Adv. 2018 Feb 27;2[4]:381-9). The pilot study enrolled 12 adults with newly diagnosed AML who received CX-01 as a continuous infusion for 7 days, along with standard induction chemotherapy (cytarabine and idarubicin).
A total of 11 patients achieved morphological complete remission after one cycle of induction. This included two patients who did not complete induction. All patients received subsequent therapy – consolidation, salvage, or transplant – on or off study.
At a median follow-up of 24 months, eight patients were still alive. Two patients died of transplant-related complications, one died of infectious complications, and one died of cerebral hemorrhage. The median disease-free survival was 14.8 months, and the median overall survival was not reached.
There were five serious adverse events in five patients; most were considered unrelated to CX-01, but a case of grade 4 sepsis was possibly related.
The FDA’s fast-track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
PLK1 inhibitor receives orphan designation for AML
The European Commission has granted orphan drug designation to onvansertib for the treatment of acute myeloid leukemia (AML).
Onvansertib (formerly PCM-075) is an oral adenosine triphosphate competitive inhibitor of the serine/threonine Polo-like kinase 1 (PLK1) enzyme, which is overexpressed in hematologic and solid tumor malignancies.
Trovagene, Inc., the company developing onvansertib, said the drug has a 24-hour half-life with reversible, on-target hematologic activity.
These factors, combined with an improved dose/scheduling protocol, could mean onvansertib will improve upon long-term outcomes observed in previous studies with a PLK inhibitor in AML.
This includes a phase 2 study in which AML patients who received a PLK inhibitor plus low-dose cytarabine (LDAC) had a higher response rate than patients who received LDAC alone—31% and 13.3%, respectively.
Trovagene said preclinical studies have shown that onvansertib synergizes with more than 10 drugs used to treat hematologic and solid tumor malignancies. This includes FLT3 and HDAC inhibitors, taxanes, and cytotoxins.
Trovagene is now conducting a phase 1b/2 trial of onvansertib in combination with standard care (LDAC or decitabine) in patients with AML (NCT03303339).
The company has already completed a phase 1 dose-escalation study of onvansertib in patients with advanced metastatic solid tumor malignancies. Results from this study were published in Investigational New Drugs.
About orphan designation
Orphan drug designation in Europe is available to companies developing products intended to treat a life-threatening or chronically debilitating condition that affects fewer than 5 in 10,000 people in the European Union (EU).
The designation allows for financial and regulatory incentives that include 10 years of marketing exclusivity in the EU after product approval, eligibility for conditional marketing authorization, protocol assistance from the European Medicines Agency at reduced fees during the product development phase, and direct access to centralized marketing authorization in the EU.
The European Commission has granted orphan drug designation to onvansertib for the treatment of acute myeloid leukemia (AML).
Onvansertib (formerly PCM-075) is an oral adenosine triphosphate competitive inhibitor of the serine/threonine Polo-like kinase 1 (PLK1) enzyme, which is overexpressed in hematologic and solid tumor malignancies.
Trovagene, Inc., the company developing onvansertib, said the drug has a 24-hour half-life with reversible, on-target hematologic activity.
These factors, combined with an improved dose/scheduling protocol, could mean onvansertib will improve upon long-term outcomes observed in previous studies with a PLK inhibitor in AML.
This includes a phase 2 study in which AML patients who received a PLK inhibitor plus low-dose cytarabine (LDAC) had a higher response rate than patients who received LDAC alone—31% and 13.3%, respectively.
Trovagene said preclinical studies have shown that onvansertib synergizes with more than 10 drugs used to treat hematologic and solid tumor malignancies. This includes FLT3 and HDAC inhibitors, taxanes, and cytotoxins.
Trovagene is now conducting a phase 1b/2 trial of onvansertib in combination with standard care (LDAC or decitabine) in patients with AML (NCT03303339).
The company has already completed a phase 1 dose-escalation study of onvansertib in patients with advanced metastatic solid tumor malignancies. Results from this study were published in Investigational New Drugs.
About orphan designation
Orphan drug designation in Europe is available to companies developing products intended to treat a life-threatening or chronically debilitating condition that affects fewer than 5 in 10,000 people in the European Union (EU).
The designation allows for financial and regulatory incentives that include 10 years of marketing exclusivity in the EU after product approval, eligibility for conditional marketing authorization, protocol assistance from the European Medicines Agency at reduced fees during the product development phase, and direct access to centralized marketing authorization in the EU.
The European Commission has granted orphan drug designation to onvansertib for the treatment of acute myeloid leukemia (AML).
Onvansertib (formerly PCM-075) is an oral adenosine triphosphate competitive inhibitor of the serine/threonine Polo-like kinase 1 (PLK1) enzyme, which is overexpressed in hematologic and solid tumor malignancies.
Trovagene, Inc., the company developing onvansertib, said the drug has a 24-hour half-life with reversible, on-target hematologic activity.
These factors, combined with an improved dose/scheduling protocol, could mean onvansertib will improve upon long-term outcomes observed in previous studies with a PLK inhibitor in AML.
This includes a phase 2 study in which AML patients who received a PLK inhibitor plus low-dose cytarabine (LDAC) had a higher response rate than patients who received LDAC alone—31% and 13.3%, respectively.
Trovagene said preclinical studies have shown that onvansertib synergizes with more than 10 drugs used to treat hematologic and solid tumor malignancies. This includes FLT3 and HDAC inhibitors, taxanes, and cytotoxins.
Trovagene is now conducting a phase 1b/2 trial of onvansertib in combination with standard care (LDAC or decitabine) in patients with AML (NCT03303339).
The company has already completed a phase 1 dose-escalation study of onvansertib in patients with advanced metastatic solid tumor malignancies. Results from this study were published in Investigational New Drugs.
About orphan designation
Orphan drug designation in Europe is available to companies developing products intended to treat a life-threatening or chronically debilitating condition that affects fewer than 5 in 10,000 people in the European Union (EU).
The designation allows for financial and regulatory incentives that include 10 years of marketing exclusivity in the EU after product approval, eligibility for conditional marketing authorization, protocol assistance from the European Medicines Agency at reduced fees during the product development phase, and direct access to centralized marketing authorization in the EU.
EC approves product for high-risk AML
The European Commission (EC) has approved CPX-351 (Vyxeos), a liposomal formulation that delivers a fixed ratio of daunorubicin and cytarabine (44 mg/100 mg).
CPX-351 is approved to treat adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.
The approval extends to all European Union member states as well as Iceland, Norway, and Liechtenstein.
The EC’s approval is supported by data from 5 studies, including a phase 3 trial.
Data from the phase 3 trial were published in the Journal of Clinical Oncology in July.
The trial enrolled 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
Patients received CPX-351 (n=153) or cytarabine and daunorubicin (7+3; n=156).
The overall remission rate—the rate of complete response (CR) plus CR with incomplete count recovery—was 47.7% in the CPX-351 arm and 33.3% in the 7+3 arm (P=0.016). The CR rate was 37.3% and 25.6%, respectively (P=0.040).
About 30% of patients went on to allogeneic hematopoietic stem cell transplant—34% in the CPX-351 arm and 25% in the 7+3 arm (P=0.098).
The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm (P=0.003). The median event-free survival was 2.53 months and 1.31 months, respectively (P=0.021).
Adverse events (AEs) that led to treatment discontinuation in the CPX-351 arm were cardiac failure (n=1), cardiomyopathy (n=1), and acute renal failure (n=1). AEs that led to treatment discontinuation in the 7+3 arm were decreased ejection fraction in 2 patients.
The most common grade 3 to 5 AEs (in the CPX-351 and 7+3 arms, respectively) were infection-related events (83.7% and 86.1%), febrile neutropenia (68.0% and 70.9%), pneumonia (19.6% and 14.6%), hypoxia (13.1% and 15.2%), and bleeding events (11.8% and 8.6%).
Ultimately, 69.3% of patients in the CPX-351 arm and 84.8% of those in the 7+3 arm died.
Deaths (in the CPX-351 and 7+3 cohorts, respectively) were due to progressive disease (n=65 and 67), AEs (n=15 and 19), cancer-related organ failure in the absence of progressive disease (n=0 and 5), and unknown/other causes (n=26 and 37).
The European Commission (EC) has approved CPX-351 (Vyxeos), a liposomal formulation that delivers a fixed ratio of daunorubicin and cytarabine (44 mg/100 mg).
CPX-351 is approved to treat adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.
The approval extends to all European Union member states as well as Iceland, Norway, and Liechtenstein.
The EC’s approval is supported by data from 5 studies, including a phase 3 trial.
Data from the phase 3 trial were published in the Journal of Clinical Oncology in July.
The trial enrolled 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
Patients received CPX-351 (n=153) or cytarabine and daunorubicin (7+3; n=156).
The overall remission rate—the rate of complete response (CR) plus CR with incomplete count recovery—was 47.7% in the CPX-351 arm and 33.3% in the 7+3 arm (P=0.016). The CR rate was 37.3% and 25.6%, respectively (P=0.040).
About 30% of patients went on to allogeneic hematopoietic stem cell transplant—34% in the CPX-351 arm and 25% in the 7+3 arm (P=0.098).
The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm (P=0.003). The median event-free survival was 2.53 months and 1.31 months, respectively (P=0.021).
Adverse events (AEs) that led to treatment discontinuation in the CPX-351 arm were cardiac failure (n=1), cardiomyopathy (n=1), and acute renal failure (n=1). AEs that led to treatment discontinuation in the 7+3 arm were decreased ejection fraction in 2 patients.
The most common grade 3 to 5 AEs (in the CPX-351 and 7+3 arms, respectively) were infection-related events (83.7% and 86.1%), febrile neutropenia (68.0% and 70.9%), pneumonia (19.6% and 14.6%), hypoxia (13.1% and 15.2%), and bleeding events (11.8% and 8.6%).
Ultimately, 69.3% of patients in the CPX-351 arm and 84.8% of those in the 7+3 arm died.
Deaths (in the CPX-351 and 7+3 cohorts, respectively) were due to progressive disease (n=65 and 67), AEs (n=15 and 19), cancer-related organ failure in the absence of progressive disease (n=0 and 5), and unknown/other causes (n=26 and 37).
The European Commission (EC) has approved CPX-351 (Vyxeos), a liposomal formulation that delivers a fixed ratio of daunorubicin and cytarabine (44 mg/100 mg).
CPX-351 is approved to treat adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.
The approval extends to all European Union member states as well as Iceland, Norway, and Liechtenstein.
The EC’s approval is supported by data from 5 studies, including a phase 3 trial.
Data from the phase 3 trial were published in the Journal of Clinical Oncology in July.
The trial enrolled 309 patients, ages 60 to 75, with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes.
Patients received CPX-351 (n=153) or cytarabine and daunorubicin (7+3; n=156).
The overall remission rate—the rate of complete response (CR) plus CR with incomplete count recovery—was 47.7% in the CPX-351 arm and 33.3% in the 7+3 arm (P=0.016). The CR rate was 37.3% and 25.6%, respectively (P=0.040).
About 30% of patients went on to allogeneic hematopoietic stem cell transplant—34% in the CPX-351 arm and 25% in the 7+3 arm (P=0.098).
The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm (P=0.003). The median event-free survival was 2.53 months and 1.31 months, respectively (P=0.021).
Adverse events (AEs) that led to treatment discontinuation in the CPX-351 arm were cardiac failure (n=1), cardiomyopathy (n=1), and acute renal failure (n=1). AEs that led to treatment discontinuation in the 7+3 arm were decreased ejection fraction in 2 patients.
The most common grade 3 to 5 AEs (in the CPX-351 and 7+3 arms, respectively) were infection-related events (83.7% and 86.1%), febrile neutropenia (68.0% and 70.9%), pneumonia (19.6% and 14.6%), hypoxia (13.1% and 15.2%), and bleeding events (11.8% and 8.6%).
Ultimately, 69.3% of patients in the CPX-351 arm and 84.8% of those in the 7+3 arm died.
Deaths (in the CPX-351 and 7+3 cohorts, respectively) were due to progressive disease (n=65 and 67), AEs (n=15 and 19), cancer-related organ failure in the absence of progressive disease (n=0 and 5), and unknown/other causes (n=26 and 37).
FDA grants fast track designation to CX-01 for AML
The US Food and Drug Administration (FDA) has granted fast track designation to CX-01 as a treatment for patients older than 60 receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).
CX-01 also has orphan drug designation from the FDA.
CX-01 is a polysaccharide derived from heparin that is thought to enhance chemotherapy by disrupting the adhesion of leukemia cells in the bone marrow.
CX-01 inhibits the activity of HMGB1, disrupts the CXCL12/CXCR4 axis, and neutralizes the activity of platelet factor 4. HMGB1 has been implicated in autophagy, a mechanism by which cells withstand the effects of chemotherapy.
The CXCL12/CXCR4 axis is thought to be involved in protecting leukemia cells from chemotherapy. And platelet factor 4 inhibits bone marrow recovery after chemotherapy.
CX-01 research
Cantex Pharmaceuticals, Inc., is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.
This study builds upon results of a pilot study, which were published in Blood Advances in February.
The study enrolled 12 adults with newly diagnosed AML. Patients had good-risk (n=3), intermediate-risk (n=5), and poor-risk (n=4) disease.
They received CX-01 as a 7-day continuous infusion, along with standard induction chemotherapy (cytarabine and idarubicin).
Eleven patients (92%) achieved morphologic complete remission after one cycle of induction. This includes two patients who did not complete induction. All patients received subsequent therapy—consolidation, salvage, or transplant—on- or off-study.
At a median follow-up of 24 months, 8 patients were still alive. Two patients died of transplant-related complications, one died of infectious complications, and one died of cerebral hemorrhage.
The median disease-free survival was 14.8 months, and the median overall survival was not reached.
There were five serious adverse events (AEs) in five patients. Most of these AEs were considered unrelated to CX-01, but a case of grade 4 sepsis was considered possibly related to CX-01.
Transient, asymptomatic, low-grade elevations of liver transaminases observed during induction were considered possibly related to CX-01. There were also transient, asymptomatic, grade 3-4 liver transaminase elevations observed during consolidation that were considered possibly related to CX-01.
The researchers said the most frequent nonserious AEs were hematologic toxicities, infectious complications, and organ toxicity complications resulting from treatment and/or the underlying leukemia.
About fast track, orphan designations
The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.
Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted fast track designation to CX-01 as a treatment for patients older than 60 receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).
CX-01 also has orphan drug designation from the FDA.
CX-01 is a polysaccharide derived from heparin that is thought to enhance chemotherapy by disrupting the adhesion of leukemia cells in the bone marrow.
CX-01 inhibits the activity of HMGB1, disrupts the CXCL12/CXCR4 axis, and neutralizes the activity of platelet factor 4. HMGB1 has been implicated in autophagy, a mechanism by which cells withstand the effects of chemotherapy.
The CXCL12/CXCR4 axis is thought to be involved in protecting leukemia cells from chemotherapy. And platelet factor 4 inhibits bone marrow recovery after chemotherapy.
CX-01 research
Cantex Pharmaceuticals, Inc., is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.
This study builds upon results of a pilot study, which were published in Blood Advances in February.
The study enrolled 12 adults with newly diagnosed AML. Patients had good-risk (n=3), intermediate-risk (n=5), and poor-risk (n=4) disease.
They received CX-01 as a 7-day continuous infusion, along with standard induction chemotherapy (cytarabine and idarubicin).
Eleven patients (92%) achieved morphologic complete remission after one cycle of induction. This includes two patients who did not complete induction. All patients received subsequent therapy—consolidation, salvage, or transplant—on- or off-study.
At a median follow-up of 24 months, 8 patients were still alive. Two patients died of transplant-related complications, one died of infectious complications, and one died of cerebral hemorrhage.
The median disease-free survival was 14.8 months, and the median overall survival was not reached.
There were five serious adverse events (AEs) in five patients. Most of these AEs were considered unrelated to CX-01, but a case of grade 4 sepsis was considered possibly related to CX-01.
Transient, asymptomatic, low-grade elevations of liver transaminases observed during induction were considered possibly related to CX-01. There were also transient, asymptomatic, grade 3-4 liver transaminase elevations observed during consolidation that were considered possibly related to CX-01.
The researchers said the most frequent nonserious AEs were hematologic toxicities, infectious complications, and organ toxicity complications resulting from treatment and/or the underlying leukemia.
About fast track, orphan designations
The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.
Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted fast track designation to CX-01 as a treatment for patients older than 60 receiving induction therapy for newly diagnosed acute myeloid leukemia (AML).
CX-01 also has orphan drug designation from the FDA.
CX-01 is a polysaccharide derived from heparin that is thought to enhance chemotherapy by disrupting the adhesion of leukemia cells in the bone marrow.
CX-01 inhibits the activity of HMGB1, disrupts the CXCL12/CXCR4 axis, and neutralizes the activity of platelet factor 4. HMGB1 has been implicated in autophagy, a mechanism by which cells withstand the effects of chemotherapy.
The CXCL12/CXCR4 axis is thought to be involved in protecting leukemia cells from chemotherapy. And platelet factor 4 inhibits bone marrow recovery after chemotherapy.
CX-01 research
Cantex Pharmaceuticals, Inc., is conducting a randomized, phase 2b study to determine whether CX-01 can improve the efficacy of frontline chemotherapy in patients with AML.
This study builds upon results of a pilot study, which were published in Blood Advances in February.
The study enrolled 12 adults with newly diagnosed AML. Patients had good-risk (n=3), intermediate-risk (n=5), and poor-risk (n=4) disease.
They received CX-01 as a 7-day continuous infusion, along with standard induction chemotherapy (cytarabine and idarubicin).
Eleven patients (92%) achieved morphologic complete remission after one cycle of induction. This includes two patients who did not complete induction. All patients received subsequent therapy—consolidation, salvage, or transplant—on- or off-study.
At a median follow-up of 24 months, 8 patients were still alive. Two patients died of transplant-related complications, one died of infectious complications, and one died of cerebral hemorrhage.
The median disease-free survival was 14.8 months, and the median overall survival was not reached.
There were five serious adverse events (AEs) in five patients. Most of these AEs were considered unrelated to CX-01, but a case of grade 4 sepsis was considered possibly related to CX-01.
Transient, asymptomatic, low-grade elevations of liver transaminases observed during induction were considered possibly related to CX-01. There were also transient, asymptomatic, grade 3-4 liver transaminase elevations observed during consolidation that were considered possibly related to CX-01.
The researchers said the most frequent nonserious AEs were hematologic toxicities, infectious complications, and organ toxicity complications resulting from treatment and/or the underlying leukemia.
About fast track, orphan designations
The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.
Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
Regimen appears effective in elderly, unfit MDS/AML
A low-intensity regimen could be an effective treatment option for elderly or unfit patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), according to researchers.
The regimen—cladribine plus low-dose cytarabine alternating with decitabine—produced a response rate of 68%.
The median disease-free survival (DFS) was 10.8 months, and the median overall survival (OS) was 13.8 months.
The regimen was considered well tolerated, although all patients experienced myelosuppression, and three-quarters developed infections that may have been treatment-related.
Tapan M. Kadia, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in The Lancet Haematology.
This phase 2 trial enrolled 118 patients with previously untreated AML or high-risk MDS. Seventeen percent of patients had therapy-related AML, 25% had secondary AML (prior MDS or myeloproliferative neoplasm [MPN]), and 15% had treated secondary AML (received treatment for MDS/MPN).
Forty-one percent of patients had an adverse risk karyotype, and 27% had a complex karyotype. Patients had a range of mutations, but the most common were in RAS, TP53, DNMT3a, NPM1, and FLT3-ITD.
Most patients (n=116) were age 60 or older, with a median age of 69. However, there were 2 patients younger than age 60. Both had “extensive” exposure to anthracycline, and one had a prior myocardial infarction.
Treatment
Patients received cladribine plus low-dose cytarabine for two cycles, alternating with decitabine for two cycles, for up to 18 cycles (28 days each).
For cycle 1, patients received cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 5 and cytarabine at 20 mg (given subcutaneously) twice daily on days 1 to 10.
Patients who achieved remission went on to receive consolidation with cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 3 and cytarabine at 20 mg twice daily on days 1 to 10, alternating with decitabine at 20 mg/m² (intravenously) on days 1 to 5.
Efficacy
The objective response rate was 68%, the rate of complete response was 58%, and the rate of complete response with incomplete count recovery was 9%.
The median DFS was 10.8 months, and the median OS was 13.8 months. The 1-year OS rate was 64%, and the 2-year OS rate was 28%.
Outcomes were better in patients with a diploid karyotype than in those with adverse karyotypes or TP53 mutation. Among patients with a diploid karyotype (n=38), the response rate was 84%, and the median OS was 19.9 months.
Among patients with adverse karyotypes (n=48), the response rate was 50%, and the median OS was 10.5 months. In patients with TP53 mutation (n=20), the response rate was 40%, and the median OS was 8.9 months.
Of all responders (n=80), 23% went on to allogeneic stem cell transplant. There was no significant difference in OS between patients who received a transplant and those who did not. The median OS was 16.4 months and 15.9 months, respectively (P=0.18).
Safety
The researchers said this regimen was generally well tolerated, but all patients experienced myelosuppression.
The most common non-hematologic adverse events (AEs) considered at least possibly related to treatment included infection (n=88), elevated total bilirubin (n=26), rash (n=13), nausea (n=13), diarrhea (n=9), ALT/AST elevation (n=7), elevated creatinine (n=7), mucositis (n=7), and constipation (n=6).
Overall, grade 3/4 non-hematologic AEs tended to occur in few patients. The exception was infections. There were 77 grade 3 infections, and two grade 4 infections.
There were 9 grade 5 infections but no other fatal AEs considered at least possibly related to treatment.
One patient (1%) died within the first 4 weeks of treatment, and 8 (7%) died within the first 8 weeks. None of these patients had responded.
“Our findings suggest that the combination of cladribine and low-dose cytarabine alternating with decitabine is a highly active and well tolerated regimen for older patients with AML,” the researchers wrote.
The team also called for a phase 3 trial comparing this regimen to hypomethylating agents.
This study was sponsored by MD Anderson and supported, in part, by the National Institutes of Health.
A low-intensity regimen could be an effective treatment option for elderly or unfit patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), according to researchers.
The regimen—cladribine plus low-dose cytarabine alternating with decitabine—produced a response rate of 68%.
The median disease-free survival (DFS) was 10.8 months, and the median overall survival (OS) was 13.8 months.
The regimen was considered well tolerated, although all patients experienced myelosuppression, and three-quarters developed infections that may have been treatment-related.
Tapan M. Kadia, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in The Lancet Haematology.
This phase 2 trial enrolled 118 patients with previously untreated AML or high-risk MDS. Seventeen percent of patients had therapy-related AML, 25% had secondary AML (prior MDS or myeloproliferative neoplasm [MPN]), and 15% had treated secondary AML (received treatment for MDS/MPN).
Forty-one percent of patients had an adverse risk karyotype, and 27% had a complex karyotype. Patients had a range of mutations, but the most common were in RAS, TP53, DNMT3a, NPM1, and FLT3-ITD.
Most patients (n=116) were age 60 or older, with a median age of 69. However, there were 2 patients younger than age 60. Both had “extensive” exposure to anthracycline, and one had a prior myocardial infarction.
Treatment
Patients received cladribine plus low-dose cytarabine for two cycles, alternating with decitabine for two cycles, for up to 18 cycles (28 days each).
For cycle 1, patients received cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 5 and cytarabine at 20 mg (given subcutaneously) twice daily on days 1 to 10.
Patients who achieved remission went on to receive consolidation with cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 3 and cytarabine at 20 mg twice daily on days 1 to 10, alternating with decitabine at 20 mg/m² (intravenously) on days 1 to 5.
Efficacy
The objective response rate was 68%, the rate of complete response was 58%, and the rate of complete response with incomplete count recovery was 9%.
The median DFS was 10.8 months, and the median OS was 13.8 months. The 1-year OS rate was 64%, and the 2-year OS rate was 28%.
Outcomes were better in patients with a diploid karyotype than in those with adverse karyotypes or TP53 mutation. Among patients with a diploid karyotype (n=38), the response rate was 84%, and the median OS was 19.9 months.
Among patients with adverse karyotypes (n=48), the response rate was 50%, and the median OS was 10.5 months. In patients with TP53 mutation (n=20), the response rate was 40%, and the median OS was 8.9 months.
Of all responders (n=80), 23% went on to allogeneic stem cell transplant. There was no significant difference in OS between patients who received a transplant and those who did not. The median OS was 16.4 months and 15.9 months, respectively (P=0.18).
Safety
The researchers said this regimen was generally well tolerated, but all patients experienced myelosuppression.
The most common non-hematologic adverse events (AEs) considered at least possibly related to treatment included infection (n=88), elevated total bilirubin (n=26), rash (n=13), nausea (n=13), diarrhea (n=9), ALT/AST elevation (n=7), elevated creatinine (n=7), mucositis (n=7), and constipation (n=6).
Overall, grade 3/4 non-hematologic AEs tended to occur in few patients. The exception was infections. There were 77 grade 3 infections, and two grade 4 infections.
There were 9 grade 5 infections but no other fatal AEs considered at least possibly related to treatment.
One patient (1%) died within the first 4 weeks of treatment, and 8 (7%) died within the first 8 weeks. None of these patients had responded.
“Our findings suggest that the combination of cladribine and low-dose cytarabine alternating with decitabine is a highly active and well tolerated regimen for older patients with AML,” the researchers wrote.
The team also called for a phase 3 trial comparing this regimen to hypomethylating agents.
This study was sponsored by MD Anderson and supported, in part, by the National Institutes of Health.
A low-intensity regimen could be an effective treatment option for elderly or unfit patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), according to researchers.
The regimen—cladribine plus low-dose cytarabine alternating with decitabine—produced a response rate of 68%.
The median disease-free survival (DFS) was 10.8 months, and the median overall survival (OS) was 13.8 months.
The regimen was considered well tolerated, although all patients experienced myelosuppression, and three-quarters developed infections that may have been treatment-related.
Tapan M. Kadia, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in The Lancet Haematology.
This phase 2 trial enrolled 118 patients with previously untreated AML or high-risk MDS. Seventeen percent of patients had therapy-related AML, 25% had secondary AML (prior MDS or myeloproliferative neoplasm [MPN]), and 15% had treated secondary AML (received treatment for MDS/MPN).
Forty-one percent of patients had an adverse risk karyotype, and 27% had a complex karyotype. Patients had a range of mutations, but the most common were in RAS, TP53, DNMT3a, NPM1, and FLT3-ITD.
Most patients (n=116) were age 60 or older, with a median age of 69. However, there were 2 patients younger than age 60. Both had “extensive” exposure to anthracycline, and one had a prior myocardial infarction.
Treatment
Patients received cladribine plus low-dose cytarabine for two cycles, alternating with decitabine for two cycles, for up to 18 cycles (28 days each).
For cycle 1, patients received cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 5 and cytarabine at 20 mg (given subcutaneously) twice daily on days 1 to 10.
Patients who achieved remission went on to receive consolidation with cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 3 and cytarabine at 20 mg twice daily on days 1 to 10, alternating with decitabine at 20 mg/m² (intravenously) on days 1 to 5.
Efficacy
The objective response rate was 68%, the rate of complete response was 58%, and the rate of complete response with incomplete count recovery was 9%.
The median DFS was 10.8 months, and the median OS was 13.8 months. The 1-year OS rate was 64%, and the 2-year OS rate was 28%.
Outcomes were better in patients with a diploid karyotype than in those with adverse karyotypes or TP53 mutation. Among patients with a diploid karyotype (n=38), the response rate was 84%, and the median OS was 19.9 months.
Among patients with adverse karyotypes (n=48), the response rate was 50%, and the median OS was 10.5 months. In patients with TP53 mutation (n=20), the response rate was 40%, and the median OS was 8.9 months.
Of all responders (n=80), 23% went on to allogeneic stem cell transplant. There was no significant difference in OS between patients who received a transplant and those who did not. The median OS was 16.4 months and 15.9 months, respectively (P=0.18).
Safety
The researchers said this regimen was generally well tolerated, but all patients experienced myelosuppression.
The most common non-hematologic adverse events (AEs) considered at least possibly related to treatment included infection (n=88), elevated total bilirubin (n=26), rash (n=13), nausea (n=13), diarrhea (n=9), ALT/AST elevation (n=7), elevated creatinine (n=7), mucositis (n=7), and constipation (n=6).
Overall, grade 3/4 non-hematologic AEs tended to occur in few patients. The exception was infections. There were 77 grade 3 infections, and two grade 4 infections.
There were 9 grade 5 infections but no other fatal AEs considered at least possibly related to treatment.
One patient (1%) died within the first 4 weeks of treatment, and 8 (7%) died within the first 8 weeks. None of these patients had responded.
“Our findings suggest that the combination of cladribine and low-dose cytarabine alternating with decitabine is a highly active and well tolerated regimen for older patients with AML,” the researchers wrote.
The team also called for a phase 3 trial comparing this regimen to hypomethylating agents.
This study was sponsored by MD Anderson and supported, in part, by the National Institutes of Health.
FDA grants orphan designation to DHODH inhibitor for AML
ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme. This second-generation DHODH inhibitor is being developed by Aslan Pharmaceuticals. The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML. Aslan expects to report interim data from this trial in the second half of 2018.
Aslan has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers. The results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to Aslan, and the drug was considered well tolerated in the volunteers.
ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to the drug sponsor. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to two orders of magnitude stronger than first-generation DHODH inhibitors, such as leflunomide and teriflunomide, but it has less toxicity.
In addition, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.
ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme. This second-generation DHODH inhibitor is being developed by Aslan Pharmaceuticals. The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML. Aslan expects to report interim data from this trial in the second half of 2018.
Aslan has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers. The results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to Aslan, and the drug was considered well tolerated in the volunteers.
ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to the drug sponsor. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to two orders of magnitude stronger than first-generation DHODH inhibitors, such as leflunomide and teriflunomide, but it has less toxicity.
In addition, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.
ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme. This second-generation DHODH inhibitor is being developed by Aslan Pharmaceuticals. The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML. Aslan expects to report interim data from this trial in the second half of 2018.
Aslan has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers. The results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to Aslan, and the drug was considered well tolerated in the volunteers.
ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to the drug sponsor. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to two orders of magnitude stronger than first-generation DHODH inhibitors, such as leflunomide and teriflunomide, but it has less toxicity.
In addition, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.
Role of SES in childhood cancer survival disparities
Socioeconomic status (SES) may explain some racial/ethnic disparities in childhood cancer survival, according to new research.
The study showed that whites had a significant survival advantage over blacks and Hispanics for several childhood cancers.
SES significantly mediated the association between race/ethnicity and survival for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, and non-Hodgkin lymphoma (NHL).
Rebecca Kehm, PhD, of Columbia University in New York, New York, and her colleagues reported these findings in Cancer alongside a related editorial.
The researchers examined population-based cancer survival data from the Surveillance, Epidemiology, and End Results database.
The team collected information on 31,866 patients, ages 0 to 19, who were diagnosed with cancer between 2000 and 2011.
Survival differences by race/ethnicity
The researchers found that whites had a significant survival advantage over blacks for the cancers listed in the following table.
| Survival—black vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.43 | 1.15-1.77 | <0.01 |
| AML | 1.68 | 1.36-2.07 | <0.001 |
| Neuroblastoma | 1.38 | 1.08-1.75 | 0.01 |
| NHL | 1.53 | 1.14-2.07 | 0.01 |
| Hodgkin lymphoma | 1.66 | 1.06-2.60 | 0.03 |
| Astrocytoma | 1.95 | 1.57-2.43 | <0.001 |
| Non-astrocytoma CNS tumor | 1.53 | 1.25-1.88 | <0.001 |
| Non-rhabdomyosarcoma STS | 1.40 | 1.06-1.84 | 0.02 |
| Rhabdomyosarcoma | 1.44 | 1.10-1.88 | 0.01 |
In addition, whites had a significant survival advantage over Hispanics for the following cancers.
| Survival—Hispanic vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.63 | 1.43-1.86 | <0.001 |
| Neuroblastoma | 1.31 | 1.04-1.65 | 0.02 |
| NHL | 1.65 | 1.29-2.12 | <0.001 |
| Astrocytoma | 1.34 | 1.10-1.64 | <0.01 |
| Wilms tumor | 1.60 | 1.04-2.45 | 0.03 |
| Germ cell tumor | 1.63 | 1.19-2.24 | <0.01 |
Impact of SES
SES significantly mediated the association between race/ethnicity and survival for ALL, AML, neuroblastoma, and NHL but not for Hodgkin lymphoma or other cancers.
For black versus white patients, SES reduced the original association between race/ethnicity and survival by:
- 44% for ALL
- 28% for AML
- 49% for neuroblastoma
- 34% for NHL.
For Hispanics versus whites, SES reduced the original association between race/ethnicity and survival by:
- 31% for ALL
- 73% for AML
- 48% for neuroblastoma
- 28% for NHL.
“These findings provide insight for future intervention efforts aimed at closing the survival gap,” Dr Kehm said.
“For cancers in which socioeconomic status is a key factor in explaining racial and ethnic survival disparities, behavioral and supportive interventions that address social and economic barriers to effective care are warranted. However, for cancers in which survival is less influenced by socioeconomic status, more research is needed on underlying differences in tumor biology and drug processing.”
This research was supported by a grant from the National Institutes of Health, and the study’s authors made no disclosures.
Socioeconomic status (SES) may explain some racial/ethnic disparities in childhood cancer survival, according to new research.
The study showed that whites had a significant survival advantage over blacks and Hispanics for several childhood cancers.
SES significantly mediated the association between race/ethnicity and survival for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, and non-Hodgkin lymphoma (NHL).
Rebecca Kehm, PhD, of Columbia University in New York, New York, and her colleagues reported these findings in Cancer alongside a related editorial.
The researchers examined population-based cancer survival data from the Surveillance, Epidemiology, and End Results database.
The team collected information on 31,866 patients, ages 0 to 19, who were diagnosed with cancer between 2000 and 2011.
Survival differences by race/ethnicity
The researchers found that whites had a significant survival advantage over blacks for the cancers listed in the following table.
| Survival—black vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.43 | 1.15-1.77 | <0.01 |
| AML | 1.68 | 1.36-2.07 | <0.001 |
| Neuroblastoma | 1.38 | 1.08-1.75 | 0.01 |
| NHL | 1.53 | 1.14-2.07 | 0.01 |
| Hodgkin lymphoma | 1.66 | 1.06-2.60 | 0.03 |
| Astrocytoma | 1.95 | 1.57-2.43 | <0.001 |
| Non-astrocytoma CNS tumor | 1.53 | 1.25-1.88 | <0.001 |
| Non-rhabdomyosarcoma STS | 1.40 | 1.06-1.84 | 0.02 |
| Rhabdomyosarcoma | 1.44 | 1.10-1.88 | 0.01 |
In addition, whites had a significant survival advantage over Hispanics for the following cancers.
| Survival—Hispanic vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.63 | 1.43-1.86 | <0.001 |
| Neuroblastoma | 1.31 | 1.04-1.65 | 0.02 |
| NHL | 1.65 | 1.29-2.12 | <0.001 |
| Astrocytoma | 1.34 | 1.10-1.64 | <0.01 |
| Wilms tumor | 1.60 | 1.04-2.45 | 0.03 |
| Germ cell tumor | 1.63 | 1.19-2.24 | <0.01 |
Impact of SES
SES significantly mediated the association between race/ethnicity and survival for ALL, AML, neuroblastoma, and NHL but not for Hodgkin lymphoma or other cancers.
For black versus white patients, SES reduced the original association between race/ethnicity and survival by:
- 44% for ALL
- 28% for AML
- 49% for neuroblastoma
- 34% for NHL.
For Hispanics versus whites, SES reduced the original association between race/ethnicity and survival by:
- 31% for ALL
- 73% for AML
- 48% for neuroblastoma
- 28% for NHL.
“These findings provide insight for future intervention efforts aimed at closing the survival gap,” Dr Kehm said.
“For cancers in which socioeconomic status is a key factor in explaining racial and ethnic survival disparities, behavioral and supportive interventions that address social and economic barriers to effective care are warranted. However, for cancers in which survival is less influenced by socioeconomic status, more research is needed on underlying differences in tumor biology and drug processing.”
This research was supported by a grant from the National Institutes of Health, and the study’s authors made no disclosures.
Socioeconomic status (SES) may explain some racial/ethnic disparities in childhood cancer survival, according to new research.
The study showed that whites had a significant survival advantage over blacks and Hispanics for several childhood cancers.
SES significantly mediated the association between race/ethnicity and survival for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, and non-Hodgkin lymphoma (NHL).
Rebecca Kehm, PhD, of Columbia University in New York, New York, and her colleagues reported these findings in Cancer alongside a related editorial.
The researchers examined population-based cancer survival data from the Surveillance, Epidemiology, and End Results database.
The team collected information on 31,866 patients, ages 0 to 19, who were diagnosed with cancer between 2000 and 2011.
Survival differences by race/ethnicity
The researchers found that whites had a significant survival advantage over blacks for the cancers listed in the following table.
| Survival—black vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.43 | 1.15-1.77 | <0.01 |
| AML | 1.68 | 1.36-2.07 | <0.001 |
| Neuroblastoma | 1.38 | 1.08-1.75 | 0.01 |
| NHL | 1.53 | 1.14-2.07 | 0.01 |
| Hodgkin lymphoma | 1.66 | 1.06-2.60 | 0.03 |
| Astrocytoma | 1.95 | 1.57-2.43 | <0.001 |
| Non-astrocytoma CNS tumor | 1.53 | 1.25-1.88 | <0.001 |
| Non-rhabdomyosarcoma STS | 1.40 | 1.06-1.84 | 0.02 |
| Rhabdomyosarcoma | 1.44 | 1.10-1.88 | 0.01 |
In addition, whites had a significant survival advantage over Hispanics for the following cancers.
| Survival—Hispanic vs white | |||
| Cancer | Mortality hazard ratio | 95% confidence interval | P value |
| ALL | 1.63 | 1.43-1.86 | <0.001 |
| Neuroblastoma | 1.31 | 1.04-1.65 | 0.02 |
| NHL | 1.65 | 1.29-2.12 | <0.001 |
| Astrocytoma | 1.34 | 1.10-1.64 | <0.01 |
| Wilms tumor | 1.60 | 1.04-2.45 | 0.03 |
| Germ cell tumor | 1.63 | 1.19-2.24 | <0.01 |
Impact of SES
SES significantly mediated the association between race/ethnicity and survival for ALL, AML, neuroblastoma, and NHL but not for Hodgkin lymphoma or other cancers.
For black versus white patients, SES reduced the original association between race/ethnicity and survival by:
- 44% for ALL
- 28% for AML
- 49% for neuroblastoma
- 34% for NHL.
For Hispanics versus whites, SES reduced the original association between race/ethnicity and survival by:
- 31% for ALL
- 73% for AML
- 48% for neuroblastoma
- 28% for NHL.
“These findings provide insight for future intervention efforts aimed at closing the survival gap,” Dr Kehm said.
“For cancers in which socioeconomic status is a key factor in explaining racial and ethnic survival disparities, behavioral and supportive interventions that address social and economic barriers to effective care are warranted. However, for cancers in which survival is less influenced by socioeconomic status, more research is needed on underlying differences in tumor biology and drug processing.”
This research was supported by a grant from the National Institutes of Health, and the study’s authors made no disclosures.
Inhibitor receives orphan designation for AML
The US Food and Drug Administration (FDA) has granted orphan drug designation to ASLAN003 as a treatment for acute myeloid leukemia (AML).
ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme.
This second-generation DHODH inhibitor is being developed by ASLAN Pharmaceuticals.
The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML.
The goals of this trial are to determine the optimum dose of ASLAN003 as monotherapy and assess the drug’s efficacy by overall complete remission rate. ASLAN expects to report interim data from this trial in the second half of this year.
ASLAN has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers.
Results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to ASLAN, and the drug was considered well tolerated in the volunteers.
ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to ASLAN. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to 2 orders of magnitude stronger than first-generation DHODH inhibitors such as leflunomide and teriflunomide.
ASLAN also said ASLAN003 should not confer the same toxicities as first-generation DHODH inhibitors and other novel AML therapies.
For example, leflunomide and teriflunomide, which may cause significant liver toxicity, take between 3 and 4 weeks to build to therapeutic levels and 2 years to be cleared completely after treatment is stopped.
ASLAN003, on the other hand, reaches full exposure in 24 hours and has a half-life of 18 hours.
Finally, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.
Because of this research, ASLAN believes ASLAN003 may be effective in patients who do not respond to all-trans retinoic acid.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ASLAN003 as a treatment for acute myeloid leukemia (AML).
ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme.
This second-generation DHODH inhibitor is being developed by ASLAN Pharmaceuticals.
The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML.
The goals of this trial are to determine the optimum dose of ASLAN003 as monotherapy and assess the drug’s efficacy by overall complete remission rate. ASLAN expects to report interim data from this trial in the second half of this year.
ASLAN has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers.
Results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to ASLAN, and the drug was considered well tolerated in the volunteers.
ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to ASLAN. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to 2 orders of magnitude stronger than first-generation DHODH inhibitors such as leflunomide and teriflunomide.
ASLAN also said ASLAN003 should not confer the same toxicities as first-generation DHODH inhibitors and other novel AML therapies.
For example, leflunomide and teriflunomide, which may cause significant liver toxicity, take between 3 and 4 weeks to build to therapeutic levels and 2 years to be cleared completely after treatment is stopped.
ASLAN003, on the other hand, reaches full exposure in 24 hours and has a half-life of 18 hours.
Finally, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.
Because of this research, ASLAN believes ASLAN003 may be effective in patients who do not respond to all-trans retinoic acid.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ASLAN003 as a treatment for acute myeloid leukemia (AML).
ASLAN003 is a small molecule inhibitor of the human dihydroorotate dehydrogenase (DHODH) enzyme.
This second-generation DHODH inhibitor is being developed by ASLAN Pharmaceuticals.
The company is currently conducting a phase 2 trial (NCT03451084) of ASLAN003 in patients with newly diagnosed or relapsed/refractory AML.
The goals of this trial are to determine the optimum dose of ASLAN003 as monotherapy and assess the drug’s efficacy by overall complete remission rate. ASLAN expects to report interim data from this trial in the second half of this year.
ASLAN has already completed a phase 1 trial (NCT01992367) of ASLAN003 in healthy volunteers.
Results suggested that ASLAN003 has an “excellent” pharmacokinetic profile, according to ASLAN, and the drug was considered well tolerated in the volunteers.
ASLAN003 has also demonstrated “potent” inhibition of DHODH, according to ASLAN. In fact, the company said the binding affinity of ASLAN003 to DHODH has proven to be up to 2 orders of magnitude stronger than first-generation DHODH inhibitors such as leflunomide and teriflunomide.
ASLAN also said ASLAN003 should not confer the same toxicities as first-generation DHODH inhibitors and other novel AML therapies.
For example, leflunomide and teriflunomide, which may cause significant liver toxicity, take between 3 and 4 weeks to build to therapeutic levels and 2 years to be cleared completely after treatment is stopped.
ASLAN003, on the other hand, reaches full exposure in 24 hours and has a half-life of 18 hours.
Finally, ASLAN003 has been shown to differentiate blast cells into granulocytes in AML cell lines that do not respond to all-trans retinoic acid. These results were published in Cell in 2016.
Because of this research, ASLAN believes ASLAN003 may be effective in patients who do not respond to all-trans retinoic acid.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
FDA puts partial hold on trial of vascular agent for AML, MDS
The Food and Drug Administration has placed a partial clinical hold on a phase 1b/2 study of OXi4503, a vascular disrupting agent.
In this trial (NCT02576301), researchers are evaluating OXi4503 alone and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The partial clinical hold applies to the 12.2 mg/m2 dose of OXi4503. The FDA is allowing the continued treatment and enrollment of patients using a dose of 9.76 mg/m2. Additional data on patients receiving OXi4503 at 9.76 mg/m2 must be evaluated before dosing at 12.2 mg/m2 can be resumed.
The partial clinical hold is a result of two potential dose-limiting toxicities (DLTs) observed at the 12.2-mg/m2 dose level: hypotension, which occurred shortly after initial treatment with OXi4503, and acute hypoxic respiratory failure, which occurred approximately 2 weeks after receiving OXi4503 and cytarabine.
Both events were deemed “possibly related” to OXi4503, and both patients recovered following treatment.
“Although it is disappointing that we are not currently continuing with the higher dose of OXi4503, we look forward to gathering more safety and efficacy data at the previous dose level, where we observed 2 complete remissions in the 4 patients that we treated,” William D. Schwieterman, MD, chief executive officer of Mateon Therapeutics Inc., the company developing OXi4503, said in a statement.
In preclinical research, OXi4503 demonstrated activity against AML, both when given alone and in combination with bevacizumab. These results were published in Blood in 2010.
In a phase 1 trial (NCT01085656), researchers evaluated OXi4503 in patients with relapsed or refractory AML or MDS. OXi4503 demonstrated preliminary evidence of disease response in heavily pretreated, refractory AML and advanced MDS.
The maximum tolerated dose of OXi4503 was not identified, but adverse events attributable to the drug included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.
Results from this study were presented at the 2013 annual meeting of the American Society of Hematology.
In 2015, Mateon Therapeutics initiated the phase 1b/2 study of OXi4503 (NCT02576301) that is now on partial clinical hold.
The phase 1 portion of this study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent OXi4503 in patients with relapsed/refractory AML and MDS. It is also aimed at determining the safety, pharmacokinetics, and pharmacodynamics of OXi4503 plus intermediate-dose cytarabine.
The goal of the phase 2 portion is to assess the preliminary efficacy of OXi4503 and cytarabine in patients with AML and MDS.
The Food and Drug Administration has placed a partial clinical hold on a phase 1b/2 study of OXi4503, a vascular disrupting agent.
In this trial (NCT02576301), researchers are evaluating OXi4503 alone and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The partial clinical hold applies to the 12.2 mg/m2 dose of OXi4503. The FDA is allowing the continued treatment and enrollment of patients using a dose of 9.76 mg/m2. Additional data on patients receiving OXi4503 at 9.76 mg/m2 must be evaluated before dosing at 12.2 mg/m2 can be resumed.
The partial clinical hold is a result of two potential dose-limiting toxicities (DLTs) observed at the 12.2-mg/m2 dose level: hypotension, which occurred shortly after initial treatment with OXi4503, and acute hypoxic respiratory failure, which occurred approximately 2 weeks after receiving OXi4503 and cytarabine.
Both events were deemed “possibly related” to OXi4503, and both patients recovered following treatment.
“Although it is disappointing that we are not currently continuing with the higher dose of OXi4503, we look forward to gathering more safety and efficacy data at the previous dose level, where we observed 2 complete remissions in the 4 patients that we treated,” William D. Schwieterman, MD, chief executive officer of Mateon Therapeutics Inc., the company developing OXi4503, said in a statement.
In preclinical research, OXi4503 demonstrated activity against AML, both when given alone and in combination with bevacizumab. These results were published in Blood in 2010.
In a phase 1 trial (NCT01085656), researchers evaluated OXi4503 in patients with relapsed or refractory AML or MDS. OXi4503 demonstrated preliminary evidence of disease response in heavily pretreated, refractory AML and advanced MDS.
The maximum tolerated dose of OXi4503 was not identified, but adverse events attributable to the drug included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.
Results from this study were presented at the 2013 annual meeting of the American Society of Hematology.
In 2015, Mateon Therapeutics initiated the phase 1b/2 study of OXi4503 (NCT02576301) that is now on partial clinical hold.
The phase 1 portion of this study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent OXi4503 in patients with relapsed/refractory AML and MDS. It is also aimed at determining the safety, pharmacokinetics, and pharmacodynamics of OXi4503 plus intermediate-dose cytarabine.
The goal of the phase 2 portion is to assess the preliminary efficacy of OXi4503 and cytarabine in patients with AML and MDS.
The Food and Drug Administration has placed a partial clinical hold on a phase 1b/2 study of OXi4503, a vascular disrupting agent.
In this trial (NCT02576301), researchers are evaluating OXi4503 alone and in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
The partial clinical hold applies to the 12.2 mg/m2 dose of OXi4503. The FDA is allowing the continued treatment and enrollment of patients using a dose of 9.76 mg/m2. Additional data on patients receiving OXi4503 at 9.76 mg/m2 must be evaluated before dosing at 12.2 mg/m2 can be resumed.
The partial clinical hold is a result of two potential dose-limiting toxicities (DLTs) observed at the 12.2-mg/m2 dose level: hypotension, which occurred shortly after initial treatment with OXi4503, and acute hypoxic respiratory failure, which occurred approximately 2 weeks after receiving OXi4503 and cytarabine.
Both events were deemed “possibly related” to OXi4503, and both patients recovered following treatment.
“Although it is disappointing that we are not currently continuing with the higher dose of OXi4503, we look forward to gathering more safety and efficacy data at the previous dose level, where we observed 2 complete remissions in the 4 patients that we treated,” William D. Schwieterman, MD, chief executive officer of Mateon Therapeutics Inc., the company developing OXi4503, said in a statement.
In preclinical research, OXi4503 demonstrated activity against AML, both when given alone and in combination with bevacizumab. These results were published in Blood in 2010.
In a phase 1 trial (NCT01085656), researchers evaluated OXi4503 in patients with relapsed or refractory AML or MDS. OXi4503 demonstrated preliminary evidence of disease response in heavily pretreated, refractory AML and advanced MDS.
The maximum tolerated dose of OXi4503 was not identified, but adverse events attributable to the drug included hypertension, bone pain, fever, anemia, thrombocytopenia, and coagulopathies.
Results from this study were presented at the 2013 annual meeting of the American Society of Hematology.
In 2015, Mateon Therapeutics initiated the phase 1b/2 study of OXi4503 (NCT02576301) that is now on partial clinical hold.
The phase 1 portion of this study was designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent OXi4503 in patients with relapsed/refractory AML and MDS. It is also aimed at determining the safety, pharmacokinetics, and pharmacodynamics of OXi4503 plus intermediate-dose cytarabine.
The goal of the phase 2 portion is to assess the preliminary efficacy of OXi4503 and cytarabine in patients with AML and MDS.
Access to care drives disparity between urban, rural cancer patients
New research suggests that better access to quality care may reduce disparities in survival between cancer patients living in rural areas of the US and those living in urban areas.
The study showed that urban and rural cancer patients had similar survival outcomes when they were enrolled in clinical trials.
These results, published in JAMA Network Open, cast new light on decades of research showing that cancer patients living in rural areas don’t live as long as urban cancer patients.
“These findings were a surprise, since we thought we might find the same disparities others had found,” said study author Joseph Unger, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.
“But clinical trials are a key difference here. In trials, patients are uniformly assessed, treated, and followed under a strict, guideline-driven protocol. This suggests that giving people with cancer access to uniform treatment strategies could help resolve the disparities in outcomes that we see between rural and urban patients.”
Dr Unger and his colleagues studied data on 36,995 patients who were enrolled in 44 phase 3 or phase 2/3 SWOG trials from 1986 through 2012. All 50 states were represented.
Patients had 17 different cancer types, including acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM).
Using US Department of Agriculture population classifications known as Rural-Urban Continuum Codes, the researchers categorized the patients as either rural or urban and analyzed their outcomes.
A minority of patients (19.4%, n=7184) were from rural locations. They were significantly more likely than urban patients to be 65 or older (P<0.001) and significantly less likely to be black (vs all other races; P<0.001).
However, there was no significant between-group difference in sex (P=0.53), and all major US geographic regions (West, Midwest, South, and Northeast) were represented.
Results
The researchers limited their analysis of survival to the first 5 years after trial enrollment to emphasize outcomes related to cancer and its treatment. They looked at overall survival (OS) as well as cancer-specific survival.
The team found no meaningful difference in OS or cancer-specific survival between rural and urban patients for 16 of the 17 cancer types.
The exception was estrogen receptor-negative, progesterone receptor-negative breast cancer. Rural patients with this cancer didn’t live as long as their urban counterparts. The hazard ratio (HR) was 1.27 (95% CI, 1.06-1.51; P=0.008) for OS and 1.26 (95% CI, 1.04-1.52; P=0.02) for cancer-specific survival.
The researchers believe this finding could be attributed to a few factors, including timely access to follow-up chemotherapy after patients’ first round of cancer treatment.
Although there were no significant survival differences for patients with hematologic malignancies, rural patients had slightly better OS if they had advanced indolent NHL or AML but slightly worse OS if they had MM or advanced aggressive NHL. The HRs were as follows:
- Advanced indolent NHL—HR=0.91 (95% CI, 0.64-1.29; P=0.60)
- AML—HR=0.94 (95% CI, 0.83-1.06; P=0.29)
- MM—HR=1.05 (95% CI, 0.93-1.18, P=0.46)
- Advanced aggressive NHL—HR=1.05 (95% CI, 0.87-1.27; P=0.60).
Rural patients had slightly better cancer-specific survival if they had advanced indolent NHL but slightly worse cancer-specific survival if they had AML, MM, or advanced aggressive NHL. The HRs were as follows:
- Advanced indolent NHL—HR=0.98 (95% CI, 0.66-1.45; P=0.90)
- AML—HR=1.01 (95% CI, 0.86-1.20; P=0.87)
- MM—HR=1.04 (95% CI, 0.90-1.20; P=0.60)
- Advanced aggressive NHL—HR=1.08 (95% CI, 0.87-1.34; P=0.50).
The researchers said these findings suggest it is access to care, and not other characteristics, that drive the survival disparities typically observed between urban and rural cancer patients.
“If people diagnosed with cancer, regardless of where they live, receive similar care and have similar outcomes, then a reasonable inference is that the best way to improve outcomes for rural patients is to improve their access to quality care,” Dr Unger said.
This research was supported by the National Cancer Institute and the HOPE Foundation. The researchers reported financial relationships with various pharmaceutical companies.
New research suggests that better access to quality care may reduce disparities in survival between cancer patients living in rural areas of the US and those living in urban areas.
The study showed that urban and rural cancer patients had similar survival outcomes when they were enrolled in clinical trials.
These results, published in JAMA Network Open, cast new light on decades of research showing that cancer patients living in rural areas don’t live as long as urban cancer patients.
“These findings were a surprise, since we thought we might find the same disparities others had found,” said study author Joseph Unger, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.
“But clinical trials are a key difference here. In trials, patients are uniformly assessed, treated, and followed under a strict, guideline-driven protocol. This suggests that giving people with cancer access to uniform treatment strategies could help resolve the disparities in outcomes that we see between rural and urban patients.”
Dr Unger and his colleagues studied data on 36,995 patients who were enrolled in 44 phase 3 or phase 2/3 SWOG trials from 1986 through 2012. All 50 states were represented.
Patients had 17 different cancer types, including acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM).
Using US Department of Agriculture population classifications known as Rural-Urban Continuum Codes, the researchers categorized the patients as either rural or urban and analyzed their outcomes.
A minority of patients (19.4%, n=7184) were from rural locations. They were significantly more likely than urban patients to be 65 or older (P<0.001) and significantly less likely to be black (vs all other races; P<0.001).
However, there was no significant between-group difference in sex (P=0.53), and all major US geographic regions (West, Midwest, South, and Northeast) were represented.
Results
The researchers limited their analysis of survival to the first 5 years after trial enrollment to emphasize outcomes related to cancer and its treatment. They looked at overall survival (OS) as well as cancer-specific survival.
The team found no meaningful difference in OS or cancer-specific survival between rural and urban patients for 16 of the 17 cancer types.
The exception was estrogen receptor-negative, progesterone receptor-negative breast cancer. Rural patients with this cancer didn’t live as long as their urban counterparts. The hazard ratio (HR) was 1.27 (95% CI, 1.06-1.51; P=0.008) for OS and 1.26 (95% CI, 1.04-1.52; P=0.02) for cancer-specific survival.
The researchers believe this finding could be attributed to a few factors, including timely access to follow-up chemotherapy after patients’ first round of cancer treatment.
Although there were no significant survival differences for patients with hematologic malignancies, rural patients had slightly better OS if they had advanced indolent NHL or AML but slightly worse OS if they had MM or advanced aggressive NHL. The HRs were as follows:
- Advanced indolent NHL—HR=0.91 (95% CI, 0.64-1.29; P=0.60)
- AML—HR=0.94 (95% CI, 0.83-1.06; P=0.29)
- MM—HR=1.05 (95% CI, 0.93-1.18, P=0.46)
- Advanced aggressive NHL—HR=1.05 (95% CI, 0.87-1.27; P=0.60).
Rural patients had slightly better cancer-specific survival if they had advanced indolent NHL but slightly worse cancer-specific survival if they had AML, MM, or advanced aggressive NHL. The HRs were as follows:
- Advanced indolent NHL—HR=0.98 (95% CI, 0.66-1.45; P=0.90)
- AML—HR=1.01 (95% CI, 0.86-1.20; P=0.87)
- MM—HR=1.04 (95% CI, 0.90-1.20; P=0.60)
- Advanced aggressive NHL—HR=1.08 (95% CI, 0.87-1.34; P=0.50).
The researchers said these findings suggest it is access to care, and not other characteristics, that drive the survival disparities typically observed between urban and rural cancer patients.
“If people diagnosed with cancer, regardless of where they live, receive similar care and have similar outcomes, then a reasonable inference is that the best way to improve outcomes for rural patients is to improve their access to quality care,” Dr Unger said.
This research was supported by the National Cancer Institute and the HOPE Foundation. The researchers reported financial relationships with various pharmaceutical companies.
New research suggests that better access to quality care may reduce disparities in survival between cancer patients living in rural areas of the US and those living in urban areas.
The study showed that urban and rural cancer patients had similar survival outcomes when they were enrolled in clinical trials.
These results, published in JAMA Network Open, cast new light on decades of research showing that cancer patients living in rural areas don’t live as long as urban cancer patients.
“These findings were a surprise, since we thought we might find the same disparities others had found,” said study author Joseph Unger, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.
“But clinical trials are a key difference here. In trials, patients are uniformly assessed, treated, and followed under a strict, guideline-driven protocol. This suggests that giving people with cancer access to uniform treatment strategies could help resolve the disparities in outcomes that we see between rural and urban patients.”
Dr Unger and his colleagues studied data on 36,995 patients who were enrolled in 44 phase 3 or phase 2/3 SWOG trials from 1986 through 2012. All 50 states were represented.
Patients had 17 different cancer types, including acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM).
Using US Department of Agriculture population classifications known as Rural-Urban Continuum Codes, the researchers categorized the patients as either rural or urban and analyzed their outcomes.
A minority of patients (19.4%, n=7184) were from rural locations. They were significantly more likely than urban patients to be 65 or older (P<0.001) and significantly less likely to be black (vs all other races; P<0.001).
However, there was no significant between-group difference in sex (P=0.53), and all major US geographic regions (West, Midwest, South, and Northeast) were represented.
Results
The researchers limited their analysis of survival to the first 5 years after trial enrollment to emphasize outcomes related to cancer and its treatment. They looked at overall survival (OS) as well as cancer-specific survival.
The team found no meaningful difference in OS or cancer-specific survival between rural and urban patients for 16 of the 17 cancer types.
The exception was estrogen receptor-negative, progesterone receptor-negative breast cancer. Rural patients with this cancer didn’t live as long as their urban counterparts. The hazard ratio (HR) was 1.27 (95% CI, 1.06-1.51; P=0.008) for OS and 1.26 (95% CI, 1.04-1.52; P=0.02) for cancer-specific survival.
The researchers believe this finding could be attributed to a few factors, including timely access to follow-up chemotherapy after patients’ first round of cancer treatment.
Although there were no significant survival differences for patients with hematologic malignancies, rural patients had slightly better OS if they had advanced indolent NHL or AML but slightly worse OS if they had MM or advanced aggressive NHL. The HRs were as follows:
- Advanced indolent NHL—HR=0.91 (95% CI, 0.64-1.29; P=0.60)
- AML—HR=0.94 (95% CI, 0.83-1.06; P=0.29)
- MM—HR=1.05 (95% CI, 0.93-1.18, P=0.46)
- Advanced aggressive NHL—HR=1.05 (95% CI, 0.87-1.27; P=0.60).
Rural patients had slightly better cancer-specific survival if they had advanced indolent NHL but slightly worse cancer-specific survival if they had AML, MM, or advanced aggressive NHL. The HRs were as follows:
- Advanced indolent NHL—HR=0.98 (95% CI, 0.66-1.45; P=0.90)
- AML—HR=1.01 (95% CI, 0.86-1.20; P=0.87)
- MM—HR=1.04 (95% CI, 0.90-1.20; P=0.60)
- Advanced aggressive NHL—HR=1.08 (95% CI, 0.87-1.34; P=0.50).
The researchers said these findings suggest it is access to care, and not other characteristics, that drive the survival disparities typically observed between urban and rural cancer patients.
“If people diagnosed with cancer, regardless of where they live, receive similar care and have similar outcomes, then a reasonable inference is that the best way to improve outcomes for rural patients is to improve their access to quality care,” Dr Unger said.
This research was supported by the National Cancer Institute and the HOPE Foundation. The researchers reported financial relationships with various pharmaceutical companies.