Will Pass

In patients with seropositive rheumatoid arthritis, seroconversion within the first year of treatment is not associated with long-term sustained drug-free remission (SDFR), according to results of a randomized, treat-to-target study of patients with early RA.

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“The clinical significance of seroconversion in RA and especially its relationship with long-term SDFR, an approximation of disease ‘cure’ of RA, is a topic of major interest,” wrote Emma C. de Moel, of the department of rheumatology at Leiden (Netherlands) University Medical Center, and her coauthors.

“Previous studies found no association of seroconversion with remission or radiographic damage,” the investigators wrote in Annals of the Rheumatic Diseases. “We here investigated the association between seroconversion and ... SDFR and found no association.”

The study involved 381 patients with early RA (less than 2 years) from the IMPROVED trial who were treated with methotrexate and high-dose prednisone. At baseline and 12 months, 14 RA-associated autoantibodies were measured by ELISA, including anti-CCP2 and rheumatoid factor. Patients were monitored for long-term SDFR, defined as remission lasting longer than 1 year, beginning at any time, and persisting until the maximum follow-up of 5 years.

An association between seroconversion and SDFR was not found. At 12 months, 6 of 170 patients (3.5%) had seroconverted all autoantibodies to negative, and 2 of these 6 patients achieved SDFR, compared with 19 of 164 seropositive patients (11.6%) who achieved SDFR without seroconversion (P = .11). Additionally, neither the proportion of autoantibodies converted to negative nor relative decreases in autoantibody levels were associated with SDFR.

“It appears that seroconversion (as measured by current standards) does not identify a group of patients in ... true immunological remission, and is not superior to signals of low inflammatory load (e.g. by DAS 6) for predicting successful drug tapering,” the investigators concluded. “Future studies are needed to identify whether other immunological parameters such as the numbers or phenotype of circulating autoreactive B or T cells might be a better reflection of disease persistence and markers for immunological remission.”

The study was funded by ZonMw (the Netherlands Organization for Health Research and Development)-consortium Molecular Diagnostics in RA (MODIRA).

SOURCE: de Moel EC et al. Ann Rheum Dis. 2018 Jul 25. doi: 10.1136/annrheumdis-2018-213823.

In patients with seropositive rheumatoid arthritis, seroconversion within the first year of treatment is not associated with long-term sustained drug-free remission (SDFR), according to results of a randomized, treat-to-target study of patients with early RA.

Suze777/Thinkstock

“The clinical significance of seroconversion in RA and especially its relationship with long-term SDFR, an approximation of disease ‘cure’ of RA, is a topic of major interest,” wrote Emma C. de Moel, of the department of rheumatology at Leiden (Netherlands) University Medical Center, and her coauthors.

“Previous studies found no association of seroconversion with remission or radiographic damage,” the investigators wrote in Annals of the Rheumatic Diseases. “We here investigated the association between seroconversion and ... SDFR and found no association.”

The study involved 381 patients with early RA (less than 2 years) from the IMPROVED trial who were treated with methotrexate and high-dose prednisone. At baseline and 12 months, 14 RA-associated autoantibodies were measured by ELISA, including anti-CCP2 and rheumatoid factor. Patients were monitored for long-term SDFR, defined as remission lasting longer than 1 year, beginning at any time, and persisting until the maximum follow-up of 5 years.

An association between seroconversion and SDFR was not found. At 12 months, 6 of 170 patients (3.5%) had seroconverted all autoantibodies to negative, and 2 of these 6 patients achieved SDFR, compared with 19 of 164 seropositive patients (11.6%) who achieved SDFR without seroconversion (P = .11). Additionally, neither the proportion of autoantibodies converted to negative nor relative decreases in autoantibody levels were associated with SDFR.

“It appears that seroconversion (as measured by current standards) does not identify a group of patients in ... true immunological remission, and is not superior to signals of low inflammatory load (e.g. by DAS 6) for predicting successful drug tapering,” the investigators concluded. “Future studies are needed to identify whether other immunological parameters such as the numbers or phenotype of circulating autoreactive B or T cells might be a better reflection of disease persistence and markers for immunological remission.”

The study was funded by ZonMw (the Netherlands Organization for Health Research and Development)-consortium Molecular Diagnostics in RA (MODIRA).

SOURCE: de Moel EC et al. Ann Rheum Dis. 2018 Jul 25. doi: 10.1136/annrheumdis-2018-213823.

In patients with seropositive rheumatoid arthritis, seroconversion within the first year of treatment is not associated with long-term sustained drug-free remission (SDFR), according to results of a randomized, treat-to-target study of patients with early RA.

Suze777/Thinkstock

“The clinical significance of seroconversion in RA and especially its relationship with long-term SDFR, an approximation of disease ‘cure’ of RA, is a topic of major interest,” wrote Emma C. de Moel, of the department of rheumatology at Leiden (Netherlands) University Medical Center, and her coauthors.

“Previous studies found no association of seroconversion with remission or radiographic damage,” the investigators wrote in Annals of the Rheumatic Diseases. “We here investigated the association between seroconversion and ... SDFR and found no association.”

The study involved 381 patients with early RA (less than 2 years) from the IMPROVED trial who were treated with methotrexate and high-dose prednisone. At baseline and 12 months, 14 RA-associated autoantibodies were measured by ELISA, including anti-CCP2 and rheumatoid factor. Patients were monitored for long-term SDFR, defined as remission lasting longer than 1 year, beginning at any time, and persisting until the maximum follow-up of 5 years.

An association between seroconversion and SDFR was not found. At 12 months, 6 of 170 patients (3.5%) had seroconverted all autoantibodies to negative, and 2 of these 6 patients achieved SDFR, compared with 19 of 164 seropositive patients (11.6%) who achieved SDFR without seroconversion (P = .11). Additionally, neither the proportion of autoantibodies converted to negative nor relative decreases in autoantibody levels were associated with SDFR.

“It appears that seroconversion (as measured by current standards) does not identify a group of patients in ... true immunological remission, and is not superior to signals of low inflammatory load (e.g. by DAS 6) for predicting successful drug tapering,” the investigators concluded. “Future studies are needed to identify whether other immunological parameters such as the numbers or phenotype of circulating autoreactive B or T cells might be a better reflection of disease persistence and markers for immunological remission.”

The study was funded by ZonMw (the Netherlands Organization for Health Research and Development)-consortium Molecular Diagnostics in RA (MODIRA).

SOURCE: de Moel EC et al. Ann Rheum Dis. 2018 Jul 25. doi: 10.1136/annrheumdis-2018-213823.

In the third-line setting, avelumab is safer than chemotherapy for patients with metastatic gastric cancer, according to a recent study.

Although no primary or secondary endpoints were met, avelumab demonstrated similar antitumor activity compared with chemotherapy, reported Yung-Jue Bang, MD, PhD, of Seoul National University College of Medicine, South Korea, and his coauthors.

“There currently are no internationally recognized treatment guidelines for patients with advanced gastric cancer/gastroesophageal junction cancer [GC/GEJC] in whom two prior lines of therapy have failed,” the investigators wrote in Annals of Oncology.

The phase 3, randomized JAVELIN Gastric 300 trial compared avelumab, an anti–programmed death ligand 1 (PD-L1) monoclonal antibody, with physician’s choice of chemotherapy in 371 patients with metastatic GC/GEJC who had received two previous lines of systemic therapy. A total of 185 patients received avelumab and 186 patients received chemotherapy. Of those in the chemotherapy group, 120 (64.5%) were given irinotecan, 50 (29.0%) were given paclitaxel, and 3 (1.6%) received best supportive care only. The primary endpoint was overall survival, and secondary endpoints were objective response rate and progression-free survival. Safety and tolerability were also evaluated.

Neither primary nor secondary endpoints were met, and no significant difference in efficacy was found between treatment arms. However, tolerability was notably better in the avelumab treatment group. Treatment-related adverse events occurred in 90 patients (48.9%) in the avelumab group, compared with 131 patients (74.0%) in the chemotherapy group. Grade 3 or higher treatment-related adverse events were also less common in the avelumab group (9.2% vs. 31.6%). In the avelumab treatment arm, 4 patients (2.2%) had grade 3 or higher immune-related adverse events (autoimmune hypothyroidism, autoimmune hepatitis, elevated AST, and colitis).

“These results demonstrate that avelumab is better tolerated than chemotherapy in patients with heavily pretreated GC/GEJC, supporting the potential of avelumab for combination or maintenance therapy, even in later stages of disease,” the investigators wrote. “Nevertheless, the optimal strategy for incorporating checkpoint inhibitors into the continuum of care for patients with advanced GC/GEJC is still unknown, and studies of alternative anti–PD-1/PD-L1 treatment strategies in earlier lines of therapy are warranted.”

The study was funded by Merck and Pfizer. Authors reported compensation from AstraZeneca, Eli Lilly, Novartis, and others.

SOURCE: Bang YJ et al. Ann Oncol. 2018 Jul 24. doi:10.1093/annonc/mdy264.

In the third-line setting, avelumab is safer than chemotherapy for patients with metastatic gastric cancer, according to a recent study.

Although no primary or secondary endpoints were met, avelumab demonstrated similar antitumor activity compared with chemotherapy, reported Yung-Jue Bang, MD, PhD, of Seoul National University College of Medicine, South Korea, and his coauthors.

“There currently are no internationally recognized treatment guidelines for patients with advanced gastric cancer/gastroesophageal junction cancer [GC/GEJC] in whom two prior lines of therapy have failed,” the investigators wrote in Annals of Oncology.

The phase 3, randomized JAVELIN Gastric 300 trial compared avelumab, an anti–programmed death ligand 1 (PD-L1) monoclonal antibody, with physician’s choice of chemotherapy in 371 patients with metastatic GC/GEJC who had received two previous lines of systemic therapy. A total of 185 patients received avelumab and 186 patients received chemotherapy. Of those in the chemotherapy group, 120 (64.5%) were given irinotecan, 50 (29.0%) were given paclitaxel, and 3 (1.6%) received best supportive care only. The primary endpoint was overall survival, and secondary endpoints were objective response rate and progression-free survival. Safety and tolerability were also evaluated.

Neither primary nor secondary endpoints were met, and no significant difference in efficacy was found between treatment arms. However, tolerability was notably better in the avelumab treatment group. Treatment-related adverse events occurred in 90 patients (48.9%) in the avelumab group, compared with 131 patients (74.0%) in the chemotherapy group. Grade 3 or higher treatment-related adverse events were also less common in the avelumab group (9.2% vs. 31.6%). In the avelumab treatment arm, 4 patients (2.2%) had grade 3 or higher immune-related adverse events (autoimmune hypothyroidism, autoimmune hepatitis, elevated AST, and colitis).

“These results demonstrate that avelumab is better tolerated than chemotherapy in patients with heavily pretreated GC/GEJC, supporting the potential of avelumab for combination or maintenance therapy, even in later stages of disease,” the investigators wrote. “Nevertheless, the optimal strategy for incorporating checkpoint inhibitors into the continuum of care for patients with advanced GC/GEJC is still unknown, and studies of alternative anti–PD-1/PD-L1 treatment strategies in earlier lines of therapy are warranted.”

The study was funded by Merck and Pfizer. Authors reported compensation from AstraZeneca, Eli Lilly, Novartis, and others.

SOURCE: Bang YJ et al. Ann Oncol. 2018 Jul 24. doi:10.1093/annonc/mdy264.

In the third-line setting, avelumab is safer than chemotherapy for patients with metastatic gastric cancer, according to a recent study.

Although no primary or secondary endpoints were met, avelumab demonstrated similar antitumor activity compared with chemotherapy, reported Yung-Jue Bang, MD, PhD, of Seoul National University College of Medicine, South Korea, and his coauthors.

“There currently are no internationally recognized treatment guidelines for patients with advanced gastric cancer/gastroesophageal junction cancer [GC/GEJC] in whom two prior lines of therapy have failed,” the investigators wrote in Annals of Oncology.

The phase 3, randomized JAVELIN Gastric 300 trial compared avelumab, an anti–programmed death ligand 1 (PD-L1) monoclonal antibody, with physician’s choice of chemotherapy in 371 patients with metastatic GC/GEJC who had received two previous lines of systemic therapy. A total of 185 patients received avelumab and 186 patients received chemotherapy. Of those in the chemotherapy group, 120 (64.5%) were given irinotecan, 50 (29.0%) were given paclitaxel, and 3 (1.6%) received best supportive care only. The primary endpoint was overall survival, and secondary endpoints were objective response rate and progression-free survival. Safety and tolerability were also evaluated.

Neither primary nor secondary endpoints were met, and no significant difference in efficacy was found between treatment arms. However, tolerability was notably better in the avelumab treatment group. Treatment-related adverse events occurred in 90 patients (48.9%) in the avelumab group, compared with 131 patients (74.0%) in the chemotherapy group. Grade 3 or higher treatment-related adverse events were also less common in the avelumab group (9.2% vs. 31.6%). In the avelumab treatment arm, 4 patients (2.2%) had grade 3 or higher immune-related adverse events (autoimmune hypothyroidism, autoimmune hepatitis, elevated AST, and colitis).

“These results demonstrate that avelumab is better tolerated than chemotherapy in patients with heavily pretreated GC/GEJC, supporting the potential of avelumab for combination or maintenance therapy, even in later stages of disease,” the investigators wrote. “Nevertheless, the optimal strategy for incorporating checkpoint inhibitors into the continuum of care for patients with advanced GC/GEJC is still unknown, and studies of alternative anti–PD-1/PD-L1 treatment strategies in earlier lines of therapy are warranted.”

The study was funded by Merck and Pfizer. Authors reported compensation from AstraZeneca, Eli Lilly, Novartis, and others.

SOURCE: Bang YJ et al. Ann Oncol. 2018 Jul 24. doi:10.1093/annonc/mdy264.

For patients with non–small cell lung cancer (NSCLC), rapid EGFR-specific genotyping reduces time to initiation (TTI) of targeted therapy, compared with current next-generation sequencing (NGS) work flows, according to a recent study.

Rapid testing maintained concordance with NGS while cutting median turnaround time in half. In addition, an ultrarapid, next-day work flow allowed several highly symptomatic patients with NSCLC to start therapy within 1 week of biopsy, reported Ibiayi Dagogo-Jack, MD, of the Massachusetts General Hospital Waltham Cancer Center and her coauthors.

Molecular testing for patients with NSCLC is necessary to select appropriate therapies; however, “genotyping by NGS requires complex bioinformatics that can create treatment delays,” the investigators wrote in JCO Precision Oncology. “Some patients with NSCLC present with symptomatic disease that requires initiation of treatment before molecular testing results are available. To our knowledge, the impact of molecular testing turnaround time on clinical decision making has not been formally assessed in NSCLC.”

For rapid testing, biopsies were collected from 243 hospitalized patients with newly diagnosed, metastatic NSCLC and were then fixed in formalin. An EGFR-specific polymerase chain reaction assay was then used to identify exon 19 deletions and L858R mutations. The ultrarapid testing phase of the study involved eight highly symptomatic patients with newly diagnosed NSCLC. Biopsy samples in this group were frozen instead of fixed. Both the rapid and ultrarapid testing results were compared with 121 historical biopsies that had been genotyped by NGS.

The rapid testing’s work flow reduced TTI from 37 days to 22 days (P = .01) while maintaining high concordance with NGS (sensitivity, 98%; specificity, 100%). Median turnaround time dropped in half from 14 days to 7 days with rapid testing (P less than .001); ultrarapid testing had a turnaround time of approximately 1 day. The median TTI for the ultrarapid group was 9 days, and several patients were able to begin therapy within 1 week.

The investigators concluded that rapid and ultrarapid testing are a cost-effective, reliable means for decreasing turnaround time and TTI for patients with newly diagnosed, metastatic NSCLC. However, concurrent NGS genotyping should still be performed because NGS results may influence future therapy sequencing. With the ultrarapid work flow, additional sampling is recommended to offset the risk of tissue failure. The investigators noted that “the growing number of actionable targets substantiates the need for diagnostic strategies that expedite molecular analysis.”

The study was funded in part by the National Institutes of Health. Authors reported compensation from Merck, Boehringer Ingelheim, Takeda, and others.

SOURCE: Dagogo-Jack et al. JCO Precis Oncol. 2018 Jul 24. doi: 10.1200/PO.17.00299.

For patients with non–small cell lung cancer (NSCLC), rapid EGFR-specific genotyping reduces time to initiation (TTI) of targeted therapy, compared with current next-generation sequencing (NGS) work flows, according to a recent study.

Rapid testing maintained concordance with NGS while cutting median turnaround time in half. In addition, an ultrarapid, next-day work flow allowed several highly symptomatic patients with NSCLC to start therapy within 1 week of biopsy, reported Ibiayi Dagogo-Jack, MD, of the Massachusetts General Hospital Waltham Cancer Center and her coauthors.

Molecular testing for patients with NSCLC is necessary to select appropriate therapies; however, “genotyping by NGS requires complex bioinformatics that can create treatment delays,” the investigators wrote in JCO Precision Oncology. “Some patients with NSCLC present with symptomatic disease that requires initiation of treatment before molecular testing results are available. To our knowledge, the impact of molecular testing turnaround time on clinical decision making has not been formally assessed in NSCLC.”

For rapid testing, biopsies were collected from 243 hospitalized patients with newly diagnosed, metastatic NSCLC and were then fixed in formalin. An EGFR-specific polymerase chain reaction assay was then used to identify exon 19 deletions and L858R mutations. The ultrarapid testing phase of the study involved eight highly symptomatic patients with newly diagnosed NSCLC. Biopsy samples in this group were frozen instead of fixed. Both the rapid and ultrarapid testing results were compared with 121 historical biopsies that had been genotyped by NGS.

The rapid testing’s work flow reduced TTI from 37 days to 22 days (P = .01) while maintaining high concordance with NGS (sensitivity, 98%; specificity, 100%). Median turnaround time dropped in half from 14 days to 7 days with rapid testing (P less than .001); ultrarapid testing had a turnaround time of approximately 1 day. The median TTI for the ultrarapid group was 9 days, and several patients were able to begin therapy within 1 week.

The investigators concluded that rapid and ultrarapid testing are a cost-effective, reliable means for decreasing turnaround time and TTI for patients with newly diagnosed, metastatic NSCLC. However, concurrent NGS genotyping should still be performed because NGS results may influence future therapy sequencing. With the ultrarapid work flow, additional sampling is recommended to offset the risk of tissue failure. The investigators noted that “the growing number of actionable targets substantiates the need for diagnostic strategies that expedite molecular analysis.”

The study was funded in part by the National Institutes of Health. Authors reported compensation from Merck, Boehringer Ingelheim, Takeda, and others.

SOURCE: Dagogo-Jack et al. JCO Precis Oncol. 2018 Jul 24. doi: 10.1200/PO.17.00299.

For patients with non–small cell lung cancer (NSCLC), rapid EGFR-specific genotyping reduces time to initiation (TTI) of targeted therapy, compared with current next-generation sequencing (NGS) work flows, according to a recent study.

Rapid testing maintained concordance with NGS while cutting median turnaround time in half. In addition, an ultrarapid, next-day work flow allowed several highly symptomatic patients with NSCLC to start therapy within 1 week of biopsy, reported Ibiayi Dagogo-Jack, MD, of the Massachusetts General Hospital Waltham Cancer Center and her coauthors.

Molecular testing for patients with NSCLC is necessary to select appropriate therapies; however, “genotyping by NGS requires complex bioinformatics that can create treatment delays,” the investigators wrote in JCO Precision Oncology. “Some patients with NSCLC present with symptomatic disease that requires initiation of treatment before molecular testing results are available. To our knowledge, the impact of molecular testing turnaround time on clinical decision making has not been formally assessed in NSCLC.”

For rapid testing, biopsies were collected from 243 hospitalized patients with newly diagnosed, metastatic NSCLC and were then fixed in formalin. An EGFR-specific polymerase chain reaction assay was then used to identify exon 19 deletions and L858R mutations. The ultrarapid testing phase of the study involved eight highly symptomatic patients with newly diagnosed NSCLC. Biopsy samples in this group were frozen instead of fixed. Both the rapid and ultrarapid testing results were compared with 121 historical biopsies that had been genotyped by NGS.

The rapid testing’s work flow reduced TTI from 37 days to 22 days (P = .01) while maintaining high concordance with NGS (sensitivity, 98%; specificity, 100%). Median turnaround time dropped in half from 14 days to 7 days with rapid testing (P less than .001); ultrarapid testing had a turnaround time of approximately 1 day. The median TTI for the ultrarapid group was 9 days, and several patients were able to begin therapy within 1 week.

The investigators concluded that rapid and ultrarapid testing are a cost-effective, reliable means for decreasing turnaround time and TTI for patients with newly diagnosed, metastatic NSCLC. However, concurrent NGS genotyping should still be performed because NGS results may influence future therapy sequencing. With the ultrarapid work flow, additional sampling is recommended to offset the risk of tissue failure. The investigators noted that “the growing number of actionable targets substantiates the need for diagnostic strategies that expedite molecular analysis.”

The study was funded in part by the National Institutes of Health. Authors reported compensation from Merck, Boehringer Ingelheim, Takeda, and others.

SOURCE: Dagogo-Jack et al. JCO Precis Oncol. 2018 Jul 24. doi: 10.1200/PO.17.00299.

Prehospital administration of plasma to trauma patients at risk for hemorrhagic shock improves odds of survival, according to the Prehospital Air Medical Plasma (PAMPer) trial.

Patients who received plasma also had a decreased median prothrombin to time ratio, compared with those who received standard-care resuscitation alone.

Spotmatik/ThinkStock

Modern trauma patients benefit “from receiving less crystalloid-based therapy and early balanced blood component–based therapy once they arrive at a facility for definitive care,” Jason L. Sperry, MD, of the University of Pittsburgh and his coauthors wrote in the New England Journal of Medicine. These newer strategies aim to mitigate coagulopathy and its associated downstream complications.

Still, “a majority of deaths from traumatic hemorrhage continue to occur in the first hours after arrival at the trauma center, which underscores the importance of the prehospital environment for early interventions that provide benefit,” the investigators noted.

The PAMPer trial (NCT01818427) examined the efficacy and safety of prehospital plasma resuscitation, comparing it with standard-care resuscitation, in severely injured patients. The phase 3, randomized, superiority trial involved 501 trauma patients at risk for hemorrhagic shock who were transported from 27 air medical bases to nine trauma centers. In total, 230 patients received prehospital plasma and standard-care resuscitation, and 271 patients received standard-care alone. Standard-care included infusion of crystalloid fluids in a goal-directed manner. Air medical bases delivered each type of care in 1-month intervals.

Patients were eligible if they exhibited severe hypotension (systolic blood pressure less than 70 mm Hg) or both hypotension (systolic blood pressure less than 90 mm Hg) and tachycardia (greater than 108 beats per minute).

Eligible patients received two units of thawed plasma, which was completely delivered before administration of any other fluids. If infusion of plasma was not complete upon arrival at the trauma center, infusion was completed before any in-hospital fluids were administered. Following preexisting local protocols, 13 of 27 air transport teams carried 2U of red blood cells. If red blood cells were delivered, then this was performed after plasma administration if the patient was still hypotensive or obviously bleeding.

The 30-day mortality rate among all patients was 29.6%. Approximately one in three patients received a prehospital red blood cell transfusion, and nearly 60% underwent surgery within 24 hours of hospital admission.

A greater percentage of patients in the standard-care group were given red blood cell transfusions, compared with those in the plasma group. The standard-care patients also received greater volumes of crystalloid solution than did those receiving plasma.

The primary outcome, 30-day mortality, was 9.8% lower for patients who received plasma, compared with patients who received standard-care alone (23.2% vs. 33.0%; P = .03). Multivariate regression analysis revealed that plasma delivery accounted for a 39% lower risk of death within 30 days, compared with standard care (P = .02). Within 3 hours of randomization, Kaplan-Meier curves revealed a separation between the two treatment groups that persisted until 30 days.

Median prothrombin to time ratio, the only statistically significant secondary outcome, was lower in the plasma group than it was in the standard-care group (1.2 vs. 1.3; P less than .001).

Other measured parameters were similar between the two main treatment groups, including rates of nosocomial infections, allergic or transfusion-related reactions, acute lung injury/acute respiratory distress syndrome, and multiorgan failure.

“Although we cannot determine the independent or additive effects of prehospital administration of plasma and packed red cells, the survival benefits attributable to plasma administration persisted after adjustment for prehospital red-cell administration, and a subgroup analysis showed no heterogeneity of the treatment effect,” the investigators wrote.

The PAMPer trial was supported by a grant from the U.S. Army Medical Research and Materiel Command. One author reported funding from Janssen Pharmaceuticals, CSL Behring, Haemonetics, and Accriva Diagnostics, as well as having been named on a patent on TLR4 inhibitors for the treatment of inflammatory and infectious disorders.

SOURCE: Sperry JL et al. N Engl J Med. 2018 Jul 26;379(4):315-26.


 

Prehospital administration of plasma to trauma patients at risk for hemorrhagic shock improves odds of survival, according to the Prehospital Air Medical Plasma (PAMPer) trial.

Patients who received plasma also had a decreased median prothrombin to time ratio, compared with those who received standard-care resuscitation alone.

Spotmatik/ThinkStock

Modern trauma patients benefit “from receiving less crystalloid-based therapy and early balanced blood component–based therapy once they arrive at a facility for definitive care,” Jason L. Sperry, MD, of the University of Pittsburgh and his coauthors wrote in the New England Journal of Medicine. These newer strategies aim to mitigate coagulopathy and its associated downstream complications.

Still, “a majority of deaths from traumatic hemorrhage continue to occur in the first hours after arrival at the trauma center, which underscores the importance of the prehospital environment for early interventions that provide benefit,” the investigators noted.

The PAMPer trial (NCT01818427) examined the efficacy and safety of prehospital plasma resuscitation, comparing it with standard-care resuscitation, in severely injured patients. The phase 3, randomized, superiority trial involved 501 trauma patients at risk for hemorrhagic shock who were transported from 27 air medical bases to nine trauma centers. In total, 230 patients received prehospital plasma and standard-care resuscitation, and 271 patients received standard-care alone. Standard-care included infusion of crystalloid fluids in a goal-directed manner. Air medical bases delivered each type of care in 1-month intervals.

Patients were eligible if they exhibited severe hypotension (systolic blood pressure less than 70 mm Hg) or both hypotension (systolic blood pressure less than 90 mm Hg) and tachycardia (greater than 108 beats per minute).

Eligible patients received two units of thawed plasma, which was completely delivered before administration of any other fluids. If infusion of plasma was not complete upon arrival at the trauma center, infusion was completed before any in-hospital fluids were administered. Following preexisting local protocols, 13 of 27 air transport teams carried 2U of red blood cells. If red blood cells were delivered, then this was performed after plasma administration if the patient was still hypotensive or obviously bleeding.

The 30-day mortality rate among all patients was 29.6%. Approximately one in three patients received a prehospital red blood cell transfusion, and nearly 60% underwent surgery within 24 hours of hospital admission.

A greater percentage of patients in the standard-care group were given red blood cell transfusions, compared with those in the plasma group. The standard-care patients also received greater volumes of crystalloid solution than did those receiving plasma.

The primary outcome, 30-day mortality, was 9.8% lower for patients who received plasma, compared with patients who received standard-care alone (23.2% vs. 33.0%; P = .03). Multivariate regression analysis revealed that plasma delivery accounted for a 39% lower risk of death within 30 days, compared with standard care (P = .02). Within 3 hours of randomization, Kaplan-Meier curves revealed a separation between the two treatment groups that persisted until 30 days.

Median prothrombin to time ratio, the only statistically significant secondary outcome, was lower in the plasma group than it was in the standard-care group (1.2 vs. 1.3; P less than .001).

Other measured parameters were similar between the two main treatment groups, including rates of nosocomial infections, allergic or transfusion-related reactions, acute lung injury/acute respiratory distress syndrome, and multiorgan failure.

“Although we cannot determine the independent or additive effects of prehospital administration of plasma and packed red cells, the survival benefits attributable to plasma administration persisted after adjustment for prehospital red-cell administration, and a subgroup analysis showed no heterogeneity of the treatment effect,” the investigators wrote.

The PAMPer trial was supported by a grant from the U.S. Army Medical Research and Materiel Command. One author reported funding from Janssen Pharmaceuticals, CSL Behring, Haemonetics, and Accriva Diagnostics, as well as having been named on a patent on TLR4 inhibitors for the treatment of inflammatory and infectious disorders.

SOURCE: Sperry JL et al. N Engl J Med. 2018 Jul 26;379(4):315-26.


 

Prehospital administration of plasma to trauma patients at risk for hemorrhagic shock improves odds of survival, according to the Prehospital Air Medical Plasma (PAMPer) trial.

Patients who received plasma also had a decreased median prothrombin to time ratio, compared with those who received standard-care resuscitation alone.

Spotmatik/ThinkStock

Modern trauma patients benefit “from receiving less crystalloid-based therapy and early balanced blood component–based therapy once they arrive at a facility for definitive care,” Jason L. Sperry, MD, of the University of Pittsburgh and his coauthors wrote in the New England Journal of Medicine. These newer strategies aim to mitigate coagulopathy and its associated downstream complications.

Still, “a majority of deaths from traumatic hemorrhage continue to occur in the first hours after arrival at the trauma center, which underscores the importance of the prehospital environment for early interventions that provide benefit,” the investigators noted.

The PAMPer trial (NCT01818427) examined the efficacy and safety of prehospital plasma resuscitation, comparing it with standard-care resuscitation, in severely injured patients. The phase 3, randomized, superiority trial involved 501 trauma patients at risk for hemorrhagic shock who were transported from 27 air medical bases to nine trauma centers. In total, 230 patients received prehospital plasma and standard-care resuscitation, and 271 patients received standard-care alone. Standard-care included infusion of crystalloid fluids in a goal-directed manner. Air medical bases delivered each type of care in 1-month intervals.

Patients were eligible if they exhibited severe hypotension (systolic blood pressure less than 70 mm Hg) or both hypotension (systolic blood pressure less than 90 mm Hg) and tachycardia (greater than 108 beats per minute).

Eligible patients received two units of thawed plasma, which was completely delivered before administration of any other fluids. If infusion of plasma was not complete upon arrival at the trauma center, infusion was completed before any in-hospital fluids were administered. Following preexisting local protocols, 13 of 27 air transport teams carried 2U of red blood cells. If red blood cells were delivered, then this was performed after plasma administration if the patient was still hypotensive or obviously bleeding.

The 30-day mortality rate among all patients was 29.6%. Approximately one in three patients received a prehospital red blood cell transfusion, and nearly 60% underwent surgery within 24 hours of hospital admission.

A greater percentage of patients in the standard-care group were given red blood cell transfusions, compared with those in the plasma group. The standard-care patients also received greater volumes of crystalloid solution than did those receiving plasma.

The primary outcome, 30-day mortality, was 9.8% lower for patients who received plasma, compared with patients who received standard-care alone (23.2% vs. 33.0%; P = .03). Multivariate regression analysis revealed that plasma delivery accounted for a 39% lower risk of death within 30 days, compared with standard care (P = .02). Within 3 hours of randomization, Kaplan-Meier curves revealed a separation between the two treatment groups that persisted until 30 days.

Median prothrombin to time ratio, the only statistically significant secondary outcome, was lower in the plasma group than it was in the standard-care group (1.2 vs. 1.3; P less than .001).

Other measured parameters were similar between the two main treatment groups, including rates of nosocomial infections, allergic or transfusion-related reactions, acute lung injury/acute respiratory distress syndrome, and multiorgan failure.

“Although we cannot determine the independent or additive effects of prehospital administration of plasma and packed red cells, the survival benefits attributable to plasma administration persisted after adjustment for prehospital red-cell administration, and a subgroup analysis showed no heterogeneity of the treatment effect,” the investigators wrote.

The PAMPer trial was supported by a grant from the U.S. Army Medical Research and Materiel Command. One author reported funding from Janssen Pharmaceuticals, CSL Behring, Haemonetics, and Accriva Diagnostics, as well as having been named on a patent on TLR4 inhibitors for the treatment of inflammatory and infectious disorders.

SOURCE: Sperry JL et al. N Engl J Med. 2018 Jul 26;379(4):315-26.


 

For adult patients with HIV, earlier treatment results in faster and more likely virologic suppression along with greater linkage to care, according to the 2018 Recommendations of the International Antiviral Society-USA (IAS-USA).

The updated treatment and prevention guidelines also have outlined drug selection, including three-drug therapy (usually as a single-tablet combination) and two-drug switch therapy, as well as discouragement of cash incentives for treatment. The guidelines, written by Michael S. Saag, MD, of the University of Alabama at Birmingham and his coauthors, were published in JAMA.

Since the previous IAS-USA guidelines were published in 2016 (JAMA. 2016;316(2):191-210), multiple studies have investigated the importance of timely antiretroviral therapy (ART). In one study, patients with HIV began ART within 24 hours of diagnosis. These patients achieved virologic suppression (fewer than 200 HIV RNA copies/mL) quicker than patients treated according to previous guidelines (medians, 1.8 months vs. 4.3 months; P = .0001). Another study found that patients who began ART immediately were more likely to achieve viral suppression at 12 months (50% vs. 34%; P = .007) and become linked to care at 3 months (68% vs. 43%). As such, the updated guidelines recommended that ART should be started as soon as possible (even without supporting laboratory results). Exceptions were maintained for patients not ready to start therapy and those at risk for immune reconstitution syndrome.

With regard to initial treatment selection, three-drug therapy is recommended, incorporating an integrase single-strand transfer inhibitor (InSTI) with 2 nucleoside reverse transcriptase inhibitors.

Single-tablet formulations are effective, well tolerated, and promote medication adherence. Dolutegravir is not recommended in women who are pregnant or may become pregnant because it may increase the risk of neural tube defects. It is unclear whether other InSTIs pose similar risks. Although two-drug regimens are not recommended for initial therapy, they may be considered as switch therapy to reduce cost and complications.

The 2018 guidelines have discouraged cash incentives for ART adherence because such programs have proven ineffective. Conversely, noncash incentives are likely to be beneficial. Further recommendations to improve outcomes were wide ranging and included identification of patients subject to food scarcity or psychiatric disorders. For the latter, chronic depression has been associated with worse outcomes – including a two-fold mortality risk – and so appropriate treatment is recommended.

The researchers concluded with a brief review of future directions for HIV treatment and prevention. Long-acting injectable and oral antiretrovirals are under investigation, along with implantable and nanoparticle therapies.

“Clinicians who care for patients with HIV have a major role in advocating for programs and their patients at the local, national, and international levels,” the authors wrote. “Advocacy should go beyond access to ART and include access to mental health and substance abuse services, as well as efforts to end policies such as HIV criminalization that impede the ability to provide evidence-based care and prevention services.”

The authors reported support from Gilead, ViiV, Merck, and other sources. The current guidelines were funded by IAS-USA.

SOURCE: Saag MS et al. JAMA. 2018;320[4]:379-96.

For adult patients with HIV, earlier treatment results in faster and more likely virologic suppression along with greater linkage to care, according to the 2018 Recommendations of the International Antiviral Society-USA (IAS-USA).

The updated treatment and prevention guidelines also have outlined drug selection, including three-drug therapy (usually as a single-tablet combination) and two-drug switch therapy, as well as discouragement of cash incentives for treatment. The guidelines, written by Michael S. Saag, MD, of the University of Alabama at Birmingham and his coauthors, were published in JAMA.

Since the previous IAS-USA guidelines were published in 2016 (JAMA. 2016;316(2):191-210), multiple studies have investigated the importance of timely antiretroviral therapy (ART). In one study, patients with HIV began ART within 24 hours of diagnosis. These patients achieved virologic suppression (fewer than 200 HIV RNA copies/mL) quicker than patients treated according to previous guidelines (medians, 1.8 months vs. 4.3 months; P = .0001). Another study found that patients who began ART immediately were more likely to achieve viral suppression at 12 months (50% vs. 34%; P = .007) and become linked to care at 3 months (68% vs. 43%). As such, the updated guidelines recommended that ART should be started as soon as possible (even without supporting laboratory results). Exceptions were maintained for patients not ready to start therapy and those at risk for immune reconstitution syndrome.

With regard to initial treatment selection, three-drug therapy is recommended, incorporating an integrase single-strand transfer inhibitor (InSTI) with 2 nucleoside reverse transcriptase inhibitors.

Single-tablet formulations are effective, well tolerated, and promote medication adherence. Dolutegravir is not recommended in women who are pregnant or may become pregnant because it may increase the risk of neural tube defects. It is unclear whether other InSTIs pose similar risks. Although two-drug regimens are not recommended for initial therapy, they may be considered as switch therapy to reduce cost and complications.

The 2018 guidelines have discouraged cash incentives for ART adherence because such programs have proven ineffective. Conversely, noncash incentives are likely to be beneficial. Further recommendations to improve outcomes were wide ranging and included identification of patients subject to food scarcity or psychiatric disorders. For the latter, chronic depression has been associated with worse outcomes – including a two-fold mortality risk – and so appropriate treatment is recommended.

The researchers concluded with a brief review of future directions for HIV treatment and prevention. Long-acting injectable and oral antiretrovirals are under investigation, along with implantable and nanoparticle therapies.

“Clinicians who care for patients with HIV have a major role in advocating for programs and their patients at the local, national, and international levels,” the authors wrote. “Advocacy should go beyond access to ART and include access to mental health and substance abuse services, as well as efforts to end policies such as HIV criminalization that impede the ability to provide evidence-based care and prevention services.”

The authors reported support from Gilead, ViiV, Merck, and other sources. The current guidelines were funded by IAS-USA.

SOURCE: Saag MS et al. JAMA. 2018;320[4]:379-96.

For adult patients with HIV, earlier treatment results in faster and more likely virologic suppression along with greater linkage to care, according to the 2018 Recommendations of the International Antiviral Society-USA (IAS-USA).

The updated treatment and prevention guidelines also have outlined drug selection, including three-drug therapy (usually as a single-tablet combination) and two-drug switch therapy, as well as discouragement of cash incentives for treatment. The guidelines, written by Michael S. Saag, MD, of the University of Alabama at Birmingham and his coauthors, were published in JAMA.

Since the previous IAS-USA guidelines were published in 2016 (JAMA. 2016;316(2):191-210), multiple studies have investigated the importance of timely antiretroviral therapy (ART). In one study, patients with HIV began ART within 24 hours of diagnosis. These patients achieved virologic suppression (fewer than 200 HIV RNA copies/mL) quicker than patients treated according to previous guidelines (medians, 1.8 months vs. 4.3 months; P = .0001). Another study found that patients who began ART immediately were more likely to achieve viral suppression at 12 months (50% vs. 34%; P = .007) and become linked to care at 3 months (68% vs. 43%). As such, the updated guidelines recommended that ART should be started as soon as possible (even without supporting laboratory results). Exceptions were maintained for patients not ready to start therapy and those at risk for immune reconstitution syndrome.

With regard to initial treatment selection, three-drug therapy is recommended, incorporating an integrase single-strand transfer inhibitor (InSTI) with 2 nucleoside reverse transcriptase inhibitors.

Single-tablet formulations are effective, well tolerated, and promote medication adherence. Dolutegravir is not recommended in women who are pregnant or may become pregnant because it may increase the risk of neural tube defects. It is unclear whether other InSTIs pose similar risks. Although two-drug regimens are not recommended for initial therapy, they may be considered as switch therapy to reduce cost and complications.

The 2018 guidelines have discouraged cash incentives for ART adherence because such programs have proven ineffective. Conversely, noncash incentives are likely to be beneficial. Further recommendations to improve outcomes were wide ranging and included identification of patients subject to food scarcity or psychiatric disorders. For the latter, chronic depression has been associated with worse outcomes – including a two-fold mortality risk – and so appropriate treatment is recommended.

The researchers concluded with a brief review of future directions for HIV treatment and prevention. Long-acting injectable and oral antiretrovirals are under investigation, along with implantable and nanoparticle therapies.

“Clinicians who care for patients with HIV have a major role in advocating for programs and their patients at the local, national, and international levels,” the authors wrote. “Advocacy should go beyond access to ART and include access to mental health and substance abuse services, as well as efforts to end policies such as HIV criminalization that impede the ability to provide evidence-based care and prevention services.”

The authors reported support from Gilead, ViiV, Merck, and other sources. The current guidelines were funded by IAS-USA.

SOURCE: Saag MS et al. JAMA. 2018;320[4]:379-96.

Since the Food and Drug Administration first approved checkpoint blockade immunotherapy (CBI) and BRAF^V600-targeted therapy in 2011, survival times for patients with melanoma brain metastases (MBMs) have significantly improved, with a 91% increase in 4-year overall survival (OS) from 7.4% to 14.1%.

“The management of advanced melanoma has traditionally been tempered by limited responses to conventional therapies, resulting in a median overall survival (OS) of less than 1 year,” wrote J. Bryan Iorgulescu, MD, of Brigham and Women’s Hospital in Boston, and his colleagues. The report was published in Cancer Immunology Research. “The landscape of advanced melanoma treatment was revolutionized” by the approval of immunotherapy agents, beginning in 2011.

The current, retrospective study involved 2,753 patients with stage IV melanoma. Patient data were drawn from the National Cancer Database, with diagnoses made between 2010 and 2015. Patient management, overall survival, and disease characteristics were evaluated.

During initial review, the researchers found that 35.8% of patients with stage IV melanoma had brain involvement. These patients were further categorized by those with MBM only (39.7%) versus those with extracranial metastatic disease (60.3%), which included involvement of lung (82.9%), liver (8.1%), bone (6.0%), and lymph nodes or distant subcutaneous skin (3%). MBM-only disease was independently predicted by both younger age and geographic location.

Patients receiving first-line CBI therapy demonstrated improved 4-year OS (28.1% vs. 11.1%; P less than.001) and median OS (12.4 months vs. 5.2 months; P less than .001).

Improvements with CBI were most dramatic in patients with MBM-only disease. In these cases, 4-year OS improved from 16.9% to 51.5% (P less than .001), while median OS jumped from 7.7 months to 56.4 months (P less than .001).

Improved OS was also associated with fewer comorbidities, younger age, management at an academic cancer center, single-fraction stereotactic radiosurgery, and resection of the MBM.

“Our findings help bridge the gaps in early clinical trials of CBIs that largely excluded stage IV melanoma patients with MBMs, with checkpoint immunotherapy demonstrating a more than doubling of the median and 4-year OS of MBMs,” the authors concluded.

SOURCE: Iorgulescu et al. Cancer Immunol Res. 2018 July 12 doi: 10.1158/2326-6066.CIR-18-0067.

Since the Food and Drug Administration first approved checkpoint blockade immunotherapy (CBI) and BRAF^V600-targeted therapy in 2011, survival times for patients with melanoma brain metastases (MBMs) have significantly improved, with a 91% increase in 4-year overall survival (OS) from 7.4% to 14.1%.

“The management of advanced melanoma has traditionally been tempered by limited responses to conventional therapies, resulting in a median overall survival (OS) of less than 1 year,” wrote J. Bryan Iorgulescu, MD, of Brigham and Women’s Hospital in Boston, and his colleagues. The report was published in Cancer Immunology Research. “The landscape of advanced melanoma treatment was revolutionized” by the approval of immunotherapy agents, beginning in 2011.

The current, retrospective study involved 2,753 patients with stage IV melanoma. Patient data were drawn from the National Cancer Database, with diagnoses made between 2010 and 2015. Patient management, overall survival, and disease characteristics were evaluated.

During initial review, the researchers found that 35.8% of patients with stage IV melanoma had brain involvement. These patients were further categorized by those with MBM only (39.7%) versus those with extracranial metastatic disease (60.3%), which included involvement of lung (82.9%), liver (8.1%), bone (6.0%), and lymph nodes or distant subcutaneous skin (3%). MBM-only disease was independently predicted by both younger age and geographic location.

Patients receiving first-line CBI therapy demonstrated improved 4-year OS (28.1% vs. 11.1%; P less than.001) and median OS (12.4 months vs. 5.2 months; P less than .001).

Improvements with CBI were most dramatic in patients with MBM-only disease. In these cases, 4-year OS improved from 16.9% to 51.5% (P less than .001), while median OS jumped from 7.7 months to 56.4 months (P less than .001).

Improved OS was also associated with fewer comorbidities, younger age, management at an academic cancer center, single-fraction stereotactic radiosurgery, and resection of the MBM.

“Our findings help bridge the gaps in early clinical trials of CBIs that largely excluded stage IV melanoma patients with MBMs, with checkpoint immunotherapy demonstrating a more than doubling of the median and 4-year OS of MBMs,” the authors concluded.

SOURCE: Iorgulescu et al. Cancer Immunol Res. 2018 July 12 doi: 10.1158/2326-6066.CIR-18-0067.

Since the Food and Drug Administration first approved checkpoint blockade immunotherapy (CBI) and BRAF^V600-targeted therapy in 2011, survival times for patients with melanoma brain metastases (MBMs) have significantly improved, with a 91% increase in 4-year overall survival (OS) from 7.4% to 14.1%.

“The management of advanced melanoma has traditionally been tempered by limited responses to conventional therapies, resulting in a median overall survival (OS) of less than 1 year,” wrote J. Bryan Iorgulescu, MD, of Brigham and Women’s Hospital in Boston, and his colleagues. The report was published in Cancer Immunology Research. “The landscape of advanced melanoma treatment was revolutionized” by the approval of immunotherapy agents, beginning in 2011.

The current, retrospective study involved 2,753 patients with stage IV melanoma. Patient data were drawn from the National Cancer Database, with diagnoses made between 2010 and 2015. Patient management, overall survival, and disease characteristics were evaluated.

During initial review, the researchers found that 35.8% of patients with stage IV melanoma had brain involvement. These patients were further categorized by those with MBM only (39.7%) versus those with extracranial metastatic disease (60.3%), which included involvement of lung (82.9%), liver (8.1%), bone (6.0%), and lymph nodes or distant subcutaneous skin (3%). MBM-only disease was independently predicted by both younger age and geographic location.

Patients receiving first-line CBI therapy demonstrated improved 4-year OS (28.1% vs. 11.1%; P less than.001) and median OS (12.4 months vs. 5.2 months; P less than .001).

Improvements with CBI were most dramatic in patients with MBM-only disease. In these cases, 4-year OS improved from 16.9% to 51.5% (P less than .001), while median OS jumped from 7.7 months to 56.4 months (P less than .001).

Improved OS was also associated with fewer comorbidities, younger age, management at an academic cancer center, single-fraction stereotactic radiosurgery, and resection of the MBM.

“Our findings help bridge the gaps in early clinical trials of CBIs that largely excluded stage IV melanoma patients with MBMs, with checkpoint immunotherapy demonstrating a more than doubling of the median and 4-year OS of MBMs,” the authors concluded.

SOURCE: Iorgulescu et al. Cancer Immunol Res. 2018 July 12 doi: 10.1158/2326-6066.CIR-18-0067.

Rural cancer survivors reported more timely care than did urban cancer survivors in a survey of 6,826 Medicare beneficiaries.

Taken as a whole, a similar quality of care was reported between the two groups, but the picture changed when racial/ethnic subgroups were considered. Non-Hispanic black and Hispanic patients in rural locations reported inferior care to their urban counterparts, investigators wrote in Cancer.

“Cancer patients living in rural areas are vulnerable and have unique health care needs,” wrote lead author Michelle A. Mollica, PhD, of the National Cancer Institute, and her colleagues. “To our knowledge, this is the first study to explore the patient’s perception of the timeliness of care in such a large, multiregion sample of cancer patients.”

In 2003, the National Academy of Medicine concluded that living in a rural environment was associated with poorer health. Existing research surrounding cancer has echoed this concern, showing that rural patients have higher rates of cancer and mortality, longer delays in diagnosis, and limited access to care.

The current, retrospective study involved 6,140 urban and 686 rural Medicare beneficiaries who were aged at least 65 years when diagnosed with either breast, lung, colorectal, or prostate cancer. Consumer Assessment of Healthcare Providers and Systems surveys were conducted between 1998 and 2013, then linked with data from the Surveillance, Epidemiology, and End Results registry program.

Surveys were conducted within 12 months of diagnosis, during which time patients were asked about their access to care as defined by two composites: “Getting Needed Care” and “Getting Care Quickly.” Getting Needed Care included ease of making appointments and receiving treatments and Getting Care Quickly questions asked about appointment delays and time spent waiting at the doctor’s office. Answers were converted to a numerical score from 0 to 100, with 0 being the worst and 100 being the best.

For both composites, mean scores for urban and rural locations were greater than 85 out of 100.

In contrast to previous studies, urban patients reported longer delays in care, scoring Getting Care Quickly 2.27 points lower than rural patients (P = .02). Pacific Islanders and non-Hispanic Asian patients from rural places reported even faster care, ranking about 8 points higher than urban patients of the same race/ethnicity.

Locality did not have a significant impact on Getting Needed Care unless race/ethnicity was also considered (P = .04). Non-Hispanic white patients from rural locations scored Getting Needed Care about 2 points higher than urban white patients, while Hispanic and non-Hispanic black patients had an opposite trend, with this rural cohort ranking Getting Needed Care lower than urban patients of the same race/ethnicity.

“Geographic residence is but one important factor in cancer care delivery,” the authors noted. “There is a need for fine-grained research looking at specific barriers for urban residents, experiences of racial/ethnic minority survivors residing in rural areas, and rural-urban differences in the clinic settings in which medical care is delivered.”

The authors had no disclosures to report.

SOURCE: Mollica MA et al. Cancer. 2018 Jun 7. doi: 10.1002/cncr.31541.

Rural cancer survivors reported more timely care than did urban cancer survivors in a survey of 6,826 Medicare beneficiaries.

Taken as a whole, a similar quality of care was reported between the two groups, but the picture changed when racial/ethnic subgroups were considered. Non-Hispanic black and Hispanic patients in rural locations reported inferior care to their urban counterparts, investigators wrote in Cancer.

“Cancer patients living in rural areas are vulnerable and have unique health care needs,” wrote lead author Michelle A. Mollica, PhD, of the National Cancer Institute, and her colleagues. “To our knowledge, this is the first study to explore the patient’s perception of the timeliness of care in such a large, multiregion sample of cancer patients.”

In 2003, the National Academy of Medicine concluded that living in a rural environment was associated with poorer health. Existing research surrounding cancer has echoed this concern, showing that rural patients have higher rates of cancer and mortality, longer delays in diagnosis, and limited access to care.

The current, retrospective study involved 6,140 urban and 686 rural Medicare beneficiaries who were aged at least 65 years when diagnosed with either breast, lung, colorectal, or prostate cancer. Consumer Assessment of Healthcare Providers and Systems surveys were conducted between 1998 and 2013, then linked with data from the Surveillance, Epidemiology, and End Results registry program.

Surveys were conducted within 12 months of diagnosis, during which time patients were asked about their access to care as defined by two composites: “Getting Needed Care” and “Getting Care Quickly.” Getting Needed Care included ease of making appointments and receiving treatments and Getting Care Quickly questions asked about appointment delays and time spent waiting at the doctor’s office. Answers were converted to a numerical score from 0 to 100, with 0 being the worst and 100 being the best.

For both composites, mean scores for urban and rural locations were greater than 85 out of 100.

In contrast to previous studies, urban patients reported longer delays in care, scoring Getting Care Quickly 2.27 points lower than rural patients (P = .02). Pacific Islanders and non-Hispanic Asian patients from rural places reported even faster care, ranking about 8 points higher than urban patients of the same race/ethnicity.

Locality did not have a significant impact on Getting Needed Care unless race/ethnicity was also considered (P = .04). Non-Hispanic white patients from rural locations scored Getting Needed Care about 2 points higher than urban white patients, while Hispanic and non-Hispanic black patients had an opposite trend, with this rural cohort ranking Getting Needed Care lower than urban patients of the same race/ethnicity.

“Geographic residence is but one important factor in cancer care delivery,” the authors noted. “There is a need for fine-grained research looking at specific barriers for urban residents, experiences of racial/ethnic minority survivors residing in rural areas, and rural-urban differences in the clinic settings in which medical care is delivered.”

The authors had no disclosures to report.

SOURCE: Mollica MA et al. Cancer. 2018 Jun 7. doi: 10.1002/cncr.31541.

Rural cancer survivors reported more timely care than did urban cancer survivors in a survey of 6,826 Medicare beneficiaries.

Taken as a whole, a similar quality of care was reported between the two groups, but the picture changed when racial/ethnic subgroups were considered. Non-Hispanic black and Hispanic patients in rural locations reported inferior care to their urban counterparts, investigators wrote in Cancer.

“Cancer patients living in rural areas are vulnerable and have unique health care needs,” wrote lead author Michelle A. Mollica, PhD, of the National Cancer Institute, and her colleagues. “To our knowledge, this is the first study to explore the patient’s perception of the timeliness of care in such a large, multiregion sample of cancer patients.”

In 2003, the National Academy of Medicine concluded that living in a rural environment was associated with poorer health. Existing research surrounding cancer has echoed this concern, showing that rural patients have higher rates of cancer and mortality, longer delays in diagnosis, and limited access to care.

The current, retrospective study involved 6,140 urban and 686 rural Medicare beneficiaries who were aged at least 65 years when diagnosed with either breast, lung, colorectal, or prostate cancer. Consumer Assessment of Healthcare Providers and Systems surveys were conducted between 1998 and 2013, then linked with data from the Surveillance, Epidemiology, and End Results registry program.

Surveys were conducted within 12 months of diagnosis, during which time patients were asked about their access to care as defined by two composites: “Getting Needed Care” and “Getting Care Quickly.” Getting Needed Care included ease of making appointments and receiving treatments and Getting Care Quickly questions asked about appointment delays and time spent waiting at the doctor’s office. Answers were converted to a numerical score from 0 to 100, with 0 being the worst and 100 being the best.

For both composites, mean scores for urban and rural locations were greater than 85 out of 100.

In contrast to previous studies, urban patients reported longer delays in care, scoring Getting Care Quickly 2.27 points lower than rural patients (P = .02). Pacific Islanders and non-Hispanic Asian patients from rural places reported even faster care, ranking about 8 points higher than urban patients of the same race/ethnicity.

Locality did not have a significant impact on Getting Needed Care unless race/ethnicity was also considered (P = .04). Non-Hispanic white patients from rural locations scored Getting Needed Care about 2 points higher than urban white patients, while Hispanic and non-Hispanic black patients had an opposite trend, with this rural cohort ranking Getting Needed Care lower than urban patients of the same race/ethnicity.

“Geographic residence is but one important factor in cancer care delivery,” the authors noted. “There is a need for fine-grained research looking at specific barriers for urban residents, experiences of racial/ethnic minority survivors residing in rural areas, and rural-urban differences in the clinic settings in which medical care is delivered.”

The authors had no disclosures to report.

SOURCE: Mollica MA et al. Cancer. 2018 Jun 7. doi: 10.1002/cncr.31541.

In patients with advanced non–small-cell lung cancer (NSCLC) without targetable mutations, the addition of pembrolizumab to first-line combination chemotherapy improves overall and progression-free survival, according to results from the phase 3 KEYNOTE-189 trial.

The researchers found that while patients in all subgroups benefited from the addition of pembrolizumab to chemotherapy, patients with a tumor proportion score of at least 50% benefited the most.

In 2017, accelerated approval was granted for pembrolizumab in combination with carboplatin and pemetrexed as first-line therapy for patients with NSCLC lacking EGFR and ALK mutations. This approval was based on response rates and progression-free survival from the KEYNOTE-024 phase 2 trial.

KEYNOTE-189 solidifies these findings, according to investigators. “Together with the results from KEYNOTE-024, the data from KEYNOTE-189 suggest that introducing immunotherapy as a first-line therapy may have a favorable long-term effect on outcomes,” wrote lead author Leena Gandhi, MD, director of the Perlmutter Cancer Center at New York University, and her colleagues. The report was published in the New England Journal of Medicine.

The double-blind, phase 3 trial assessed 616 treatment-naive patients with metastatic nonsquamous NSCLC without ALK or EGFR mutations. Patients received a platinum-based drug and pemetrexed plus placebo or 200 mg of pembrolizumab every 3 weeks for four cycles. After this, patients received placebo or pembrolizumab with pemetrexed maintenance therapy for up to 35 cycles. Primary endpoints were overall and progression-free survival, determined by a blinded radiologist.

At 12 months, the estimated overall survival was 69.2% for patients treated with pembrolizumab plus chemotherapy, compared with 49.4% for patients treated with chemotherapy alone. For patients treated with the pembrolizumab combination, median progression-free survival was 8.8 months, compared with 4.9 months for those treated with just chemotherapy. Median follow-up time was 10.5 months.

“The survival benefit associated with the pembrolizumab combination was observed in all subgroups of PD-L1 tumor proportion scores,” the authors wrote, “including patients with a score of less than 1%, a population for which single-agent PD-1 and PD-L1 inhibition have a small chance of benefit.” As with previous studies, the subgroup of patients with a tumor proportion score greater than or equal to 50% received the greatest benefit when pembrolizumab was added.

The authors noted that further research is needed to determine whether patients with high PD-L1 expression (TMS ≥ 50%) would benefit more from pembrolizumab combination therapy compared with pembrolizumab monotherapy, which is currently indicated.

SOURCE: Gandhi et al. N Engl J Med. 2018 May 31. doi: 10.1056/NEJMoa1801005.

In patients with advanced non–small-cell lung cancer (NSCLC) without targetable mutations, the addition of pembrolizumab to first-line combination chemotherapy improves overall and progression-free survival, according to results from the phase 3 KEYNOTE-189 trial.

The researchers found that while patients in all subgroups benefited from the addition of pembrolizumab to chemotherapy, patients with a tumor proportion score of at least 50% benefited the most.

In 2017, accelerated approval was granted for pembrolizumab in combination with carboplatin and pemetrexed as first-line therapy for patients with NSCLC lacking EGFR and ALK mutations. This approval was based on response rates and progression-free survival from the KEYNOTE-024 phase 2 trial.

KEYNOTE-189 solidifies these findings, according to investigators. “Together with the results from KEYNOTE-024, the data from KEYNOTE-189 suggest that introducing immunotherapy as a first-line therapy may have a favorable long-term effect on outcomes,” wrote lead author Leena Gandhi, MD, director of the Perlmutter Cancer Center at New York University, and her colleagues. The report was published in the New England Journal of Medicine.

The double-blind, phase 3 trial assessed 616 treatment-naive patients with metastatic nonsquamous NSCLC without ALK or EGFR mutations. Patients received a platinum-based drug and pemetrexed plus placebo or 200 mg of pembrolizumab every 3 weeks for four cycles. After this, patients received placebo or pembrolizumab with pemetrexed maintenance therapy for up to 35 cycles. Primary endpoints were overall and progression-free survival, determined by a blinded radiologist.

At 12 months, the estimated overall survival was 69.2% for patients treated with pembrolizumab plus chemotherapy, compared with 49.4% for patients treated with chemotherapy alone. For patients treated with the pembrolizumab combination, median progression-free survival was 8.8 months, compared with 4.9 months for those treated with just chemotherapy. Median follow-up time was 10.5 months.

“The survival benefit associated with the pembrolizumab combination was observed in all subgroups of PD-L1 tumor proportion scores,” the authors wrote, “including patients with a score of less than 1%, a population for which single-agent PD-1 and PD-L1 inhibition have a small chance of benefit.” As with previous studies, the subgroup of patients with a tumor proportion score greater than or equal to 50% received the greatest benefit when pembrolizumab was added.

The authors noted that further research is needed to determine whether patients with high PD-L1 expression (TMS ≥ 50%) would benefit more from pembrolizumab combination therapy compared with pembrolizumab monotherapy, which is currently indicated.

SOURCE: Gandhi et al. N Engl J Med. 2018 May 31. doi: 10.1056/NEJMoa1801005.

In patients with advanced non–small-cell lung cancer (NSCLC) without targetable mutations, the addition of pembrolizumab to first-line combination chemotherapy improves overall and progression-free survival, according to results from the phase 3 KEYNOTE-189 trial.

The researchers found that while patients in all subgroups benefited from the addition of pembrolizumab to chemotherapy, patients with a tumor proportion score of at least 50% benefited the most.

In 2017, accelerated approval was granted for pembrolizumab in combination with carboplatin and pemetrexed as first-line therapy for patients with NSCLC lacking EGFR and ALK mutations. This approval was based on response rates and progression-free survival from the KEYNOTE-024 phase 2 trial.

KEYNOTE-189 solidifies these findings, according to investigators. “Together with the results from KEYNOTE-024, the data from KEYNOTE-189 suggest that introducing immunotherapy as a first-line therapy may have a favorable long-term effect on outcomes,” wrote lead author Leena Gandhi, MD, director of the Perlmutter Cancer Center at New York University, and her colleagues. The report was published in the New England Journal of Medicine.

The double-blind, phase 3 trial assessed 616 treatment-naive patients with metastatic nonsquamous NSCLC without ALK or EGFR mutations. Patients received a platinum-based drug and pemetrexed plus placebo or 200 mg of pembrolizumab every 3 weeks for four cycles. After this, patients received placebo or pembrolizumab with pemetrexed maintenance therapy for up to 35 cycles. Primary endpoints were overall and progression-free survival, determined by a blinded radiologist.

At 12 months, the estimated overall survival was 69.2% for patients treated with pembrolizumab plus chemotherapy, compared with 49.4% for patients treated with chemotherapy alone. For patients treated with the pembrolizumab combination, median progression-free survival was 8.8 months, compared with 4.9 months for those treated with just chemotherapy. Median follow-up time was 10.5 months.

“The survival benefit associated with the pembrolizumab combination was observed in all subgroups of PD-L1 tumor proportion scores,” the authors wrote, “including patients with a score of less than 1%, a population for which single-agent PD-1 and PD-L1 inhibition have a small chance of benefit.” As with previous studies, the subgroup of patients with a tumor proportion score greater than or equal to 50% received the greatest benefit when pembrolizumab was added.

The authors noted that further research is needed to determine whether patients with high PD-L1 expression (TMS ≥ 50%) would benefit more from pembrolizumab combination therapy compared with pembrolizumab monotherapy, which is currently indicated.

SOURCE: Gandhi et al. N Engl J Med. 2018 May 31. doi: 10.1056/NEJMoa1801005.

For patients with non–small-cell lung cancer (NSCLC), preexisting autoimmune disease (AID) does not increase the risk of immune-related adverse events (irAEs) with checkpoint inhibitor therapy, according to investigators.

Flares of AID during therapy were generally mild, and toxicity rates were only slightly increased in patients with AID, they wrote in Journal of Clinical Oncology.

Approximately 14%-25% of patients with lung cancer also have AID, but patients with AID are typically excluded from clinical trials. “This presents a tremendous knowledge gap,” wrote lead author Giulia C. Leonardi, MD, of the Dana-Farber Cancer Institute in Boston, and coauthors.

The retrospective study comprised 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers. Almost half of the patients had a rheumatologic disorder, 29% had a dermatologic disorder, 16% had an endocrine disorder, 11% had inflammatory bowel disease, 5% had a neurologic condition, 3% had rheumatic fever, and one patient (2%) had autoimmune hemolytic anemia.

Patients received either a programmed death-1 or programmed death-ligand 1 inhibitor as monotherapy. Median treatment time was 3.1 months, and median follow-up time after starting therapy was 17.5 months.

Eleven percent of patients with preexisting AID developed grade 3 or 4 irAEs, which is similar to 7%-15% of patients in clinical trials. Although 23% of patients experienced a flare of their preexisting AID, these flares were generally mild – no patients discontinued immunotherapy because of a flare. In contrast, 14% of patients halted therapy because of toxicity, a marginally higher number than 3%-8% of patients in trials.

Checkpoint inhibitors are now a mainstay treatment for a lung cancer, including three approved drugs: nivolumab, pembrolizumab, and atezolizumab. “Almost every patient with advanced NSCLC will likely receive a [checkpoint] inhibitor at some point over the course of their disease,” the authors noted. As checkpoint inhibitors may lead to fatal irAEs, the possible interplay between these immunotherapies and AID requires investigation.

“Our study adds to the growing body of evidence supporting the use of immunotherapy in patients with cancer with preexisting AID, albeit with close monitoring for adverse events,” the researchers concluded.

SOURCE: Leonardi GC et al. J Clin Oncol. 2018* May 20. doi: 10.1200/JCO.2017.77.0305.

*Correction, 5/22/18: An earlier version of this article misstated the year in this citation.

For patients with non–small-cell lung cancer (NSCLC), preexisting autoimmune disease (AID) does not increase the risk of immune-related adverse events (irAEs) with checkpoint inhibitor therapy, according to investigators.

Flares of AID during therapy were generally mild, and toxicity rates were only slightly increased in patients with AID, they wrote in Journal of Clinical Oncology.

Approximately 14%-25% of patients with lung cancer also have AID, but patients with AID are typically excluded from clinical trials. “This presents a tremendous knowledge gap,” wrote lead author Giulia C. Leonardi, MD, of the Dana-Farber Cancer Institute in Boston, and coauthors.

The retrospective study comprised 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers. Almost half of the patients had a rheumatologic disorder, 29% had a dermatologic disorder, 16% had an endocrine disorder, 11% had inflammatory bowel disease, 5% had a neurologic condition, 3% had rheumatic fever, and one patient (2%) had autoimmune hemolytic anemia.

Patients received either a programmed death-1 or programmed death-ligand 1 inhibitor as monotherapy. Median treatment time was 3.1 months, and median follow-up time after starting therapy was 17.5 months.

Eleven percent of patients with preexisting AID developed grade 3 or 4 irAEs, which is similar to 7%-15% of patients in clinical trials. Although 23% of patients experienced a flare of their preexisting AID, these flares were generally mild – no patients discontinued immunotherapy because of a flare. In contrast, 14% of patients halted therapy because of toxicity, a marginally higher number than 3%-8% of patients in trials.

Checkpoint inhibitors are now a mainstay treatment for a lung cancer, including three approved drugs: nivolumab, pembrolizumab, and atezolizumab. “Almost every patient with advanced NSCLC will likely receive a [checkpoint] inhibitor at some point over the course of their disease,” the authors noted. As checkpoint inhibitors may lead to fatal irAEs, the possible interplay between these immunotherapies and AID requires investigation.

“Our study adds to the growing body of evidence supporting the use of immunotherapy in patients with cancer with preexisting AID, albeit with close monitoring for adverse events,” the researchers concluded.

SOURCE: Leonardi GC et al. J Clin Oncol. 2018* May 20. doi: 10.1200/JCO.2017.77.0305.

*Correction, 5/22/18: An earlier version of this article misstated the year in this citation.

For patients with non–small-cell lung cancer (NSCLC), preexisting autoimmune disease (AID) does not increase the risk of immune-related adverse events (irAEs) with checkpoint inhibitor therapy, according to investigators.

Flares of AID during therapy were generally mild, and toxicity rates were only slightly increased in patients with AID, they wrote in Journal of Clinical Oncology.

Approximately 14%-25% of patients with lung cancer also have AID, but patients with AID are typically excluded from clinical trials. “This presents a tremendous knowledge gap,” wrote lead author Giulia C. Leonardi, MD, of the Dana-Farber Cancer Institute in Boston, and coauthors.

The retrospective study comprised 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers. Almost half of the patients had a rheumatologic disorder, 29% had a dermatologic disorder, 16% had an endocrine disorder, 11% had inflammatory bowel disease, 5% had a neurologic condition, 3% had rheumatic fever, and one patient (2%) had autoimmune hemolytic anemia.

Patients received either a programmed death-1 or programmed death-ligand 1 inhibitor as monotherapy. Median treatment time was 3.1 months, and median follow-up time after starting therapy was 17.5 months.

Eleven percent of patients with preexisting AID developed grade 3 or 4 irAEs, which is similar to 7%-15% of patients in clinical trials. Although 23% of patients experienced a flare of their preexisting AID, these flares were generally mild – no patients discontinued immunotherapy because of a flare. In contrast, 14% of patients halted therapy because of toxicity, a marginally higher number than 3%-8% of patients in trials.

Checkpoint inhibitors are now a mainstay treatment for a lung cancer, including three approved drugs: nivolumab, pembrolizumab, and atezolizumab. “Almost every patient with advanced NSCLC will likely receive a [checkpoint] inhibitor at some point over the course of their disease,” the authors noted. As checkpoint inhibitors may lead to fatal irAEs, the possible interplay between these immunotherapies and AID requires investigation.

“Our study adds to the growing body of evidence supporting the use of immunotherapy in patients with cancer with preexisting AID, albeit with close monitoring for adverse events,” the researchers concluded.

SOURCE: Leonardi GC et al. J Clin Oncol. 2018* May 20. doi: 10.1200/JCO.2017.77.0305.

*Correction, 5/22/18: An earlier version of this article misstated the year in this citation.