2018 ASCO Annual Meeting

CHICAGO – William J. Gradishar, MD, discussed the clinical impact of breast cancer research presented at the annual meeting of the American Society of Clinical Oncology.

In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, said TAILORx was a “big win” in that it has no doubt diminished the number of women with early-stage breast cancer who will require chemotherapy. However, although the trial has provided some clarity, it also has left some questions open, particularly for patients under 50 years of age, he said.

Dr. Gradishar also discussed the results of combination trials of targeted therapy with either endocrine therapy or chemotherapy. In discussing SANDPIPER, which evaluated whether a phosphoinositide 3-kinase inhibitor could enhance the effect of anti-hormonal therapy, he said that although it was a positive trial, “from a clinician’s standpoint, it’s probably not sufficient in my mind to get really excited about.”

[email protected]

CHICAGO – William J. Gradishar, MD, discussed the clinical impact of breast cancer research presented at the annual meeting of the American Society of Clinical Oncology.

In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, said TAILORx was a “big win” in that it has no doubt diminished the number of women with early-stage breast cancer who will require chemotherapy. However, although the trial has provided some clarity, it also has left some questions open, particularly for patients under 50 years of age, he said.

Dr. Gradishar also discussed the results of combination trials of targeted therapy with either endocrine therapy or chemotherapy. In discussing SANDPIPER, which evaluated whether a phosphoinositide 3-kinase inhibitor could enhance the effect of anti-hormonal therapy, he said that although it was a positive trial, “from a clinician’s standpoint, it’s probably not sufficient in my mind to get really excited about.”

[email protected]

CHICAGO – William J. Gradishar, MD, discussed the clinical impact of breast cancer research presented at the annual meeting of the American Society of Clinical Oncology.

In a video interview, Dr. Gradishar, the Betsy Bramsen Professor of Breast Oncology at Northwestern University, Chicago, said TAILORx was a “big win” in that it has no doubt diminished the number of women with early-stage breast cancer who will require chemotherapy. However, although the trial has provided some clarity, it also has left some questions open, particularly for patients under 50 years of age, he said.

Dr. Gradishar also discussed the results of combination trials of targeted therapy with either endocrine therapy or chemotherapy. In discussing SANDPIPER, which evaluated whether a phosphoinositide 3-kinase inhibitor could enhance the effect of anti-hormonal therapy, he said that although it was a positive trial, “from a clinician’s standpoint, it’s probably not sufficient in my mind to get really excited about.”

[email protected]

CHICAGO – Elderly cancer patients have better communication with their oncologists and report greater satisfaction with their care when the oncologists are provided with geriatric assessment summaries prior to the patient visit.

Although “satisfaction” can be subjective, the conclusion about the benefit of previsit geriatric assessments is objective, reported Supriya Gupta Mohile, MD, of the University of Rochester, New York.

Neil Osterweil/MDedge News

Each domain independently predicts morbidity and/or mortality in older patients.

The investigators enrolled 31 oncology practices in the National Cancer Institute’s Community Oncology Research Program that were treating patients aged 70 or older with advanced solid tumors or lymphoma. Patients who were enrolled had at least one impaired GA domain. In all, 542 patients across the sites were enrolled.

All patients in each arm completed the GA.

Randomization was by practice, with practices in arm 1 randomized to receive GA intervention results. Oncologists in this trial arm were provided with a GA summary and list of recommended GA-guided interventions.

Practices in arm 2 (controls) did not receive summaries or lists of recommendations, but oncologists were notified if patients had clinically significant depression or cognitive impairment.

In the intervention group, patients completed all assessments within 30 minutes, and less than 10 minutes of practice staff time was required for administration of objective tests.

The investigators made audio recordings and transcripts of clinic visits after GA in both arms, with two blinded coders evaluating quality of communication and plans for follow-up interventions. Patients were surveyed by telephone about their satisfaction, via the Health Care Climate Questionnaire (HCCQ) and the same instrument modified for age-related concerns (HCCQ-age).

“We found that patients enrolled in the study had a high prevalence of impairments of Geriatric Assessment domains, ranging from over 90% for physical performance, to 25% for psychological status, mainly depression. Of note, more than 30% of patients ... screened positive for cognitive impairment.” Dr. Mohile said.

For the coprimary endpoint of communication about age-related concerns, the mean number of discussions was 7.74 in the GA arm, compared with 4.24 in the control arm, a difference of 3.5 (P less than .0001).

Arm 1 was rated as having more discussions with higher-quality communications (mean 4.42 vs. 2.47, P less than .0001), and had more discussions leading to an intervention (3.08 vs. 1.15, P less than .0001).

Patients in arm 1 consistently rated their satisfaction with communication (the other coprimary endpoint) higher than did patients in arm 2, at both baseline, 4-6 weeks after the visit, and 3 months after the visit.

Neil Osterweil/MDedge News

“This is a very important study that I think is likely to have a direct impact on the care of older patients with cancer,” ASCO expert Joshua A. Jones, MD, of the University of Pennsylvania, Philadelphia, said at the meeting.

“This study shows in a randomized fashion that we can, with a simple intervention, improve communication about what’s really important to older patients with cancer,” he said. “We have interventions, things like physical therapy, things like counseling, supports that can be provided to patients and families as they are thinking through treatment decisions, helping us to provide the most appropriate care for these individuals.”

SOURCE: Mohile SG et al. ASCO 2018, abstract LBA10003.

CHICAGO – Elderly cancer patients have better communication with their oncologists and report greater satisfaction with their care when the oncologists are provided with geriatric assessment summaries prior to the patient visit.

Although “satisfaction” can be subjective, the conclusion about the benefit of previsit geriatric assessments is objective, reported Supriya Gupta Mohile, MD, of the University of Rochester, New York.

Neil Osterweil/MDedge News

Each domain independently predicts morbidity and/or mortality in older patients.

The investigators enrolled 31 oncology practices in the National Cancer Institute’s Community Oncology Research Program that were treating patients aged 70 or older with advanced solid tumors or lymphoma. Patients who were enrolled had at least one impaired GA domain. In all, 542 patients across the sites were enrolled.

All patients in each arm completed the GA.

Randomization was by practice, with practices in arm 1 randomized to receive GA intervention results. Oncologists in this trial arm were provided with a GA summary and list of recommended GA-guided interventions.

Practices in arm 2 (controls) did not receive summaries or lists of recommendations, but oncologists were notified if patients had clinically significant depression or cognitive impairment.

In the intervention group, patients completed all assessments within 30 minutes, and less than 10 minutes of practice staff time was required for administration of objective tests.

The investigators made audio recordings and transcripts of clinic visits after GA in both arms, with two blinded coders evaluating quality of communication and plans for follow-up interventions. Patients were surveyed by telephone about their satisfaction, via the Health Care Climate Questionnaire (HCCQ) and the same instrument modified for age-related concerns (HCCQ-age).

“We found that patients enrolled in the study had a high prevalence of impairments of Geriatric Assessment domains, ranging from over 90% for physical performance, to 25% for psychological status, mainly depression. Of note, more than 30% of patients ... screened positive for cognitive impairment.” Dr. Mohile said.

For the coprimary endpoint of communication about age-related concerns, the mean number of discussions was 7.74 in the GA arm, compared with 4.24 in the control arm, a difference of 3.5 (P less than .0001).

Arm 1 was rated as having more discussions with higher-quality communications (mean 4.42 vs. 2.47, P less than .0001), and had more discussions leading to an intervention (3.08 vs. 1.15, P less than .0001).

Patients in arm 1 consistently rated their satisfaction with communication (the other coprimary endpoint) higher than did patients in arm 2, at both baseline, 4-6 weeks after the visit, and 3 months after the visit.

Neil Osterweil/MDedge News

“This is a very important study that I think is likely to have a direct impact on the care of older patients with cancer,” ASCO expert Joshua A. Jones, MD, of the University of Pennsylvania, Philadelphia, said at the meeting.

“This study shows in a randomized fashion that we can, with a simple intervention, improve communication about what’s really important to older patients with cancer,” he said. “We have interventions, things like physical therapy, things like counseling, supports that can be provided to patients and families as they are thinking through treatment decisions, helping us to provide the most appropriate care for these individuals.”

SOURCE: Mohile SG et al. ASCO 2018, abstract LBA10003.

CHICAGO – Elderly cancer patients have better communication with their oncologists and report greater satisfaction with their care when the oncologists are provided with geriatric assessment summaries prior to the patient visit.

Although “satisfaction” can be subjective, the conclusion about the benefit of previsit geriatric assessments is objective, reported Supriya Gupta Mohile, MD, of the University of Rochester, New York.

Neil Osterweil/MDedge News

Each domain independently predicts morbidity and/or mortality in older patients.

The investigators enrolled 31 oncology practices in the National Cancer Institute’s Community Oncology Research Program that were treating patients aged 70 or older with advanced solid tumors or lymphoma. Patients who were enrolled had at least one impaired GA domain. In all, 542 patients across the sites were enrolled.

All patients in each arm completed the GA.

Randomization was by practice, with practices in arm 1 randomized to receive GA intervention results. Oncologists in this trial arm were provided with a GA summary and list of recommended GA-guided interventions.

Practices in arm 2 (controls) did not receive summaries or lists of recommendations, but oncologists were notified if patients had clinically significant depression or cognitive impairment.

In the intervention group, patients completed all assessments within 30 minutes, and less than 10 minutes of practice staff time was required for administration of objective tests.

The investigators made audio recordings and transcripts of clinic visits after GA in both arms, with two blinded coders evaluating quality of communication and plans for follow-up interventions. Patients were surveyed by telephone about their satisfaction, via the Health Care Climate Questionnaire (HCCQ) and the same instrument modified for age-related concerns (HCCQ-age).

“We found that patients enrolled in the study had a high prevalence of impairments of Geriatric Assessment domains, ranging from over 90% for physical performance, to 25% for psychological status, mainly depression. Of note, more than 30% of patients ... screened positive for cognitive impairment.” Dr. Mohile said.

For the coprimary endpoint of communication about age-related concerns, the mean number of discussions was 7.74 in the GA arm, compared with 4.24 in the control arm, a difference of 3.5 (P less than .0001).

Arm 1 was rated as having more discussions with higher-quality communications (mean 4.42 vs. 2.47, P less than .0001), and had more discussions leading to an intervention (3.08 vs. 1.15, P less than .0001).

Patients in arm 1 consistently rated their satisfaction with communication (the other coprimary endpoint) higher than did patients in arm 2, at both baseline, 4-6 weeks after the visit, and 3 months after the visit.

Neil Osterweil/MDedge News

“This is a very important study that I think is likely to have a direct impact on the care of older patients with cancer,” ASCO expert Joshua A. Jones, MD, of the University of Pennsylvania, Philadelphia, said at the meeting.

“This study shows in a randomized fashion that we can, with a simple intervention, improve communication about what’s really important to older patients with cancer,” he said. “We have interventions, things like physical therapy, things like counseling, supports that can be provided to patients and families as they are thinking through treatment decisions, helping us to provide the most appropriate care for these individuals.”

SOURCE: Mohile SG et al. ASCO 2018, abstract LBA10003.

©ASCO/Todd Buchanan 2018

CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.

Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.

Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*

The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).

For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.

Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.

Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.

Results

Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.

Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.

Patients had an estimated 3-year progression-free survival of 52%.

Three patients died, all from disease progression, and 13 patients have progressed.

The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.

One patient experienced graft failure and was rescued with an autologous back-up graft.

"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."

Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.

Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 10⁸ NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.

Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”

Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.

It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.

The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.  

*Data in the presentation differ from the abstract.

©ASCO/Todd Buchanan 2018

CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.

Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.

Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*

The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).

For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.

Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.

Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.

Results

Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.

Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.

Patients had an estimated 3-year progression-free survival of 52%.

Three patients died, all from disease progression, and 13 patients have progressed.

The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.

One patient experienced graft failure and was rescued with an autologous back-up graft.

"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."

Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.

Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 10⁸ NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.

Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”

Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.

It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.

The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.  

*Data in the presentation differ from the abstract.

©ASCO/Todd Buchanan 2018

CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.

Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.

Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*

The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).

For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.

Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.

Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.

Results

Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.

Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.

Patients had an estimated 3-year progression-free survival of 52%.

Three patients died, all from disease progression, and 13 patients have progressed.

The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.

One patient experienced graft failure and was rescued with an autologous back-up graft.

"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."

Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.

Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 10⁸ NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.

Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”

Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.

It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.

The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.  

*Data in the presentation differ from the abstract.

CHICAGO – Pembrolizumab monotherapy is associated with antitumor activity in patients with advanced recurrent ovarian cancer, interim results from the phase 2 KEYNOTE-100 study suggest.

Notably, objective response rates among study subjects increased in tandem with increased programmed death-ligand 1 (PD-L1) expression, which helps define the population most likely to benefit from single agent pembrolizumab (Keytruda), Ursula A. Matulonis reported during an oral abstract session at the annual meeting of the American Society of Clinical Oncology.

Further, no new safety signals were identified, said Dr. Matulonis, medical director and program leader of the Medical Gynecologic Oncology Program at of Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.

All patients received intravenous pembrolizumab at 200 mg every 3 weeks for 2 years or until progression, death, unacceptable toxicity, or consent withdrawal, and tumor imaging was performed every 9 weeks for a year, then every 12 weeks thereafter until progressive disease, death, or study completion.

The overall response rate (ORR) among 285 patients in Cohort A, who had one to three prior chemotherapy lines for recurrent advanced ovarian cancer and a platinum-free or treatment-free interval of 3-12 months, was 7.4%, with mean duration of response of 8.2 months. The ORR among 91 patients in Cohort B, who had four to six prior chemotherapy lines and a platinum-free or treatment-free interval of at least 3 months, was 9.9%; the mean duration of response was not reached in Cohort B.

Among all-comers, the ORR was 8.0%, including 7 complete responses and 23 partial responses. Mean duration of response was 8.2 months, and 65.5% of responses lasted at least 6 months. Further, responses were observed across all subgroups, Dr. Matulonis said, noting that responses were seen regardless of age, prior lines of treatment, progression-free/treatment-free interval duration, platinum sensitivity, and histology.

“The one factor that did predict response was a [combined positive score] of 10 or higher, where there were more responses,” she said.

The ORRs among those with PD-L1 expression as measured using the combined positive score (CPS), which is defined as the number of PD-L1–positive cells out of the total number of tumor cells x 100, was 5.0% in those with CPS less than 1, 10.2% in those with CPS of 1 or greater, and 17.1% in those with CPS of 10 or greater (vs. the 8.0% ORR in the study), she explained, noting that all complete responses occurred in those with CPS of 10 or higher.

Grade 3-4 treatment-related adverse events occurred in 19.7% of patients, and included fatigue in 2.7%, and anemia, colitis, increased amylase, increased blood alkaline phosphatase, ascites, and diarrhea in 0.8-1.3%. One treatment-related death occurred in a patient with Stevens-Johnson syndrome, and another occurred in a patient with hypoaldosteronism. Immune-mediated adverse events and infusion reactions were most commonly hyperthyroidism and hypothyroidism, and most cases were grade 1-2, she said.

KEYNOTE-100 is an ongoing study that followed KEYNOTE-028, which demonstrated the clinical activity of pembrolizumab in patients with advanced ovarian cancer. To date, KEYNOTE-100 has enrolled 376 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer and confirmed recurrence after frontline platinum-based therapy. All had a tumor sample available for biomarker analysis.

The patients had a mean age of 61 years, 64% and 35% had performance status scores of 0 and 1, respectively, and 75% had high-grade serous disease.

Median follow-up in Cohort A at the time of the current analysis was 16.7 months, and in Cohort B, the median follow-up was 17.3 months. Treatment was ongoing in 15 and 6 patients in the cohorts, respectively. Reasons for discontinuation included radiographic progression (204 and 62 patients), clinical progression (24 and 17 patients), adverse events (22 and 3 patients), and patient withdrawal (9 and 3 patients). Complete responses occurred in 1 and 0 patients in the groups, respectively.

Median progression-free survival in both cohorts was 2.1 months, and overall survival was not reached in Cohort A, while it was 17.6 months in the more heavily pretreated Cohort B.

“Recurrent ovarian cancer is the leading cause of death from gynecologic cancer. The majority of our patients relapse after first-line platinum and taxane-based chemotherapy, and the degree of platinum sensitivity will predict the tumor response rates with platinum, as well as survival time,” she said, noting that subsequent recurrences become increasingly platinum and treatment resistant.

Current treatment options in these patients include chemotherapy with or without bevacizumab; the ORRs with single-agent immune checkpoint blockade are about 10%, but in KEYNOTE-028, patients with PD-L1–positive advanced recurrent ovarian cancer had an ORR of 11.5% with pembrolizumab treatment, she said.

“With 16.9 months median follow-up, the results confirm that pembrolizumab monotherapy in recurrent ovarian cancer elicits modest antitumor efficacy,” Dr. Matulonis concluded, noting that further analysis for biomarkers predictive of pembrolizumab response are ongoing.

Invited discussant Janos Laszlo Tanyi, MD, of the University of Pennsylvania, Philadelphia, said the findings underscore the overall modest ORRs of 5.9%-15% seen with anti-PD-1 or PD-L1 monotherapy in patients with advanced recurrent ovarian cancer, but noted the importance of the finding that the subpopulation of patients with increased PD-L1 expression may experience greater benefit.

Dr. Matulonis reported consulting or advisory roles with 2X Oncology, Clovis Oncology, Fujifilm, Geneos Therapeutics, Lilly, Merck, and Myriad Genetics, and research funding from Merck and Novartis. Dr .Tanyi reported having no disclosures.

SOURCE: Matulonis UA et al. ASCO 2018, Abstract 5511.

CHICAGO – Pembrolizumab monotherapy is associated with antitumor activity in patients with advanced recurrent ovarian cancer, interim results from the phase 2 KEYNOTE-100 study suggest.

Notably, objective response rates among study subjects increased in tandem with increased programmed death-ligand 1 (PD-L1) expression, which helps define the population most likely to benefit from single agent pembrolizumab (Keytruda), Ursula A. Matulonis reported during an oral abstract session at the annual meeting of the American Society of Clinical Oncology.

Further, no new safety signals were identified, said Dr. Matulonis, medical director and program leader of the Medical Gynecologic Oncology Program at of Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.

All patients received intravenous pembrolizumab at 200 mg every 3 weeks for 2 years or until progression, death, unacceptable toxicity, or consent withdrawal, and tumor imaging was performed every 9 weeks for a year, then every 12 weeks thereafter until progressive disease, death, or study completion.

The overall response rate (ORR) among 285 patients in Cohort A, who had one to three prior chemotherapy lines for recurrent advanced ovarian cancer and a platinum-free or treatment-free interval of 3-12 months, was 7.4%, with mean duration of response of 8.2 months. The ORR among 91 patients in Cohort B, who had four to six prior chemotherapy lines and a platinum-free or treatment-free interval of at least 3 months, was 9.9%; the mean duration of response was not reached in Cohort B.

Among all-comers, the ORR was 8.0%, including 7 complete responses and 23 partial responses. Mean duration of response was 8.2 months, and 65.5% of responses lasted at least 6 months. Further, responses were observed across all subgroups, Dr. Matulonis said, noting that responses were seen regardless of age, prior lines of treatment, progression-free/treatment-free interval duration, platinum sensitivity, and histology.

“The one factor that did predict response was a [combined positive score] of 10 or higher, where there were more responses,” she said.

The ORRs among those with PD-L1 expression as measured using the combined positive score (CPS), which is defined as the number of PD-L1–positive cells out of the total number of tumor cells x 100, was 5.0% in those with CPS less than 1, 10.2% in those with CPS of 1 or greater, and 17.1% in those with CPS of 10 or greater (vs. the 8.0% ORR in the study), she explained, noting that all complete responses occurred in those with CPS of 10 or higher.

Grade 3-4 treatment-related adverse events occurred in 19.7% of patients, and included fatigue in 2.7%, and anemia, colitis, increased amylase, increased blood alkaline phosphatase, ascites, and diarrhea in 0.8-1.3%. One treatment-related death occurred in a patient with Stevens-Johnson syndrome, and another occurred in a patient with hypoaldosteronism. Immune-mediated adverse events and infusion reactions were most commonly hyperthyroidism and hypothyroidism, and most cases were grade 1-2, she said.

KEYNOTE-100 is an ongoing study that followed KEYNOTE-028, which demonstrated the clinical activity of pembrolizumab in patients with advanced ovarian cancer. To date, KEYNOTE-100 has enrolled 376 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer and confirmed recurrence after frontline platinum-based therapy. All had a tumor sample available for biomarker analysis.

The patients had a mean age of 61 years, 64% and 35% had performance status scores of 0 and 1, respectively, and 75% had high-grade serous disease.

Median follow-up in Cohort A at the time of the current analysis was 16.7 months, and in Cohort B, the median follow-up was 17.3 months. Treatment was ongoing in 15 and 6 patients in the cohorts, respectively. Reasons for discontinuation included radiographic progression (204 and 62 patients), clinical progression (24 and 17 patients), adverse events (22 and 3 patients), and patient withdrawal (9 and 3 patients). Complete responses occurred in 1 and 0 patients in the groups, respectively.

Median progression-free survival in both cohorts was 2.1 months, and overall survival was not reached in Cohort A, while it was 17.6 months in the more heavily pretreated Cohort B.

“Recurrent ovarian cancer is the leading cause of death from gynecologic cancer. The majority of our patients relapse after first-line platinum and taxane-based chemotherapy, and the degree of platinum sensitivity will predict the tumor response rates with platinum, as well as survival time,” she said, noting that subsequent recurrences become increasingly platinum and treatment resistant.

Current treatment options in these patients include chemotherapy with or without bevacizumab; the ORRs with single-agent immune checkpoint blockade are about 10%, but in KEYNOTE-028, patients with PD-L1–positive advanced recurrent ovarian cancer had an ORR of 11.5% with pembrolizumab treatment, she said.

“With 16.9 months median follow-up, the results confirm that pembrolizumab monotherapy in recurrent ovarian cancer elicits modest antitumor efficacy,” Dr. Matulonis concluded, noting that further analysis for biomarkers predictive of pembrolizumab response are ongoing.

Invited discussant Janos Laszlo Tanyi, MD, of the University of Pennsylvania, Philadelphia, said the findings underscore the overall modest ORRs of 5.9%-15% seen with anti-PD-1 or PD-L1 monotherapy in patients with advanced recurrent ovarian cancer, but noted the importance of the finding that the subpopulation of patients with increased PD-L1 expression may experience greater benefit.

Dr. Matulonis reported consulting or advisory roles with 2X Oncology, Clovis Oncology, Fujifilm, Geneos Therapeutics, Lilly, Merck, and Myriad Genetics, and research funding from Merck and Novartis. Dr .Tanyi reported having no disclosures.

SOURCE: Matulonis UA et al. ASCO 2018, Abstract 5511.

CHICAGO – Pembrolizumab monotherapy is associated with antitumor activity in patients with advanced recurrent ovarian cancer, interim results from the phase 2 KEYNOTE-100 study suggest.

Notably, objective response rates among study subjects increased in tandem with increased programmed death-ligand 1 (PD-L1) expression, which helps define the population most likely to benefit from single agent pembrolizumab (Keytruda), Ursula A. Matulonis reported during an oral abstract session at the annual meeting of the American Society of Clinical Oncology.

Further, no new safety signals were identified, said Dr. Matulonis, medical director and program leader of the Medical Gynecologic Oncology Program at of Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.

All patients received intravenous pembrolizumab at 200 mg every 3 weeks for 2 years or until progression, death, unacceptable toxicity, or consent withdrawal, and tumor imaging was performed every 9 weeks for a year, then every 12 weeks thereafter until progressive disease, death, or study completion.

The overall response rate (ORR) among 285 patients in Cohort A, who had one to three prior chemotherapy lines for recurrent advanced ovarian cancer and a platinum-free or treatment-free interval of 3-12 months, was 7.4%, with mean duration of response of 8.2 months. The ORR among 91 patients in Cohort B, who had four to six prior chemotherapy lines and a platinum-free or treatment-free interval of at least 3 months, was 9.9%; the mean duration of response was not reached in Cohort B.

Among all-comers, the ORR was 8.0%, including 7 complete responses and 23 partial responses. Mean duration of response was 8.2 months, and 65.5% of responses lasted at least 6 months. Further, responses were observed across all subgroups, Dr. Matulonis said, noting that responses were seen regardless of age, prior lines of treatment, progression-free/treatment-free interval duration, platinum sensitivity, and histology.

“The one factor that did predict response was a [combined positive score] of 10 or higher, where there were more responses,” she said.

The ORRs among those with PD-L1 expression as measured using the combined positive score (CPS), which is defined as the number of PD-L1–positive cells out of the total number of tumor cells x 100, was 5.0% in those with CPS less than 1, 10.2% in those with CPS of 1 or greater, and 17.1% in those with CPS of 10 or greater (vs. the 8.0% ORR in the study), she explained, noting that all complete responses occurred in those with CPS of 10 or higher.

Grade 3-4 treatment-related adverse events occurred in 19.7% of patients, and included fatigue in 2.7%, and anemia, colitis, increased amylase, increased blood alkaline phosphatase, ascites, and diarrhea in 0.8-1.3%. One treatment-related death occurred in a patient with Stevens-Johnson syndrome, and another occurred in a patient with hypoaldosteronism. Immune-mediated adverse events and infusion reactions were most commonly hyperthyroidism and hypothyroidism, and most cases were grade 1-2, she said.

KEYNOTE-100 is an ongoing study that followed KEYNOTE-028, which demonstrated the clinical activity of pembrolizumab in patients with advanced ovarian cancer. To date, KEYNOTE-100 has enrolled 376 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer and confirmed recurrence after frontline platinum-based therapy. All had a tumor sample available for biomarker analysis.

The patients had a mean age of 61 years, 64% and 35% had performance status scores of 0 and 1, respectively, and 75% had high-grade serous disease.

Median follow-up in Cohort A at the time of the current analysis was 16.7 months, and in Cohort B, the median follow-up was 17.3 months. Treatment was ongoing in 15 and 6 patients in the cohorts, respectively. Reasons for discontinuation included radiographic progression (204 and 62 patients), clinical progression (24 and 17 patients), adverse events (22 and 3 patients), and patient withdrawal (9 and 3 patients). Complete responses occurred in 1 and 0 patients in the groups, respectively.

Median progression-free survival in both cohorts was 2.1 months, and overall survival was not reached in Cohort A, while it was 17.6 months in the more heavily pretreated Cohort B.

“Recurrent ovarian cancer is the leading cause of death from gynecologic cancer. The majority of our patients relapse after first-line platinum and taxane-based chemotherapy, and the degree of platinum sensitivity will predict the tumor response rates with platinum, as well as survival time,” she said, noting that subsequent recurrences become increasingly platinum and treatment resistant.

Current treatment options in these patients include chemotherapy with or without bevacizumab; the ORRs with single-agent immune checkpoint blockade are about 10%, but in KEYNOTE-028, patients with PD-L1–positive advanced recurrent ovarian cancer had an ORR of 11.5% with pembrolizumab treatment, she said.

“With 16.9 months median follow-up, the results confirm that pembrolizumab monotherapy in recurrent ovarian cancer elicits modest antitumor efficacy,” Dr. Matulonis concluded, noting that further analysis for biomarkers predictive of pembrolizumab response are ongoing.

Invited discussant Janos Laszlo Tanyi, MD, of the University of Pennsylvania, Philadelphia, said the findings underscore the overall modest ORRs of 5.9%-15% seen with anti-PD-1 or PD-L1 monotherapy in patients with advanced recurrent ovarian cancer, but noted the importance of the finding that the subpopulation of patients with increased PD-L1 expression may experience greater benefit.

Dr. Matulonis reported consulting or advisory roles with 2X Oncology, Clovis Oncology, Fujifilm, Geneos Therapeutics, Lilly, Merck, and Myriad Genetics, and research funding from Merck and Novartis. Dr .Tanyi reported having no disclosures.

SOURCE: Matulonis UA et al. ASCO 2018, Abstract 5511.

CHICAGO – Denosumab may be preferable to bisphosphonates in myeloma patients in specific scenarios, G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.

Andrew D. Bowser/MDedge News

The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.

The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).

Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).

The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.

Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.

Dr. Roodman reported that he had a consulting or advisory role with Amgen.

CHICAGO – Denosumab may be preferable to bisphosphonates in myeloma patients in specific scenarios, G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.

Andrew D. Bowser/MDedge News

The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.

The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).

Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).

The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.

Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.

Dr. Roodman reported that he had a consulting or advisory role with Amgen.

CHICAGO – Denosumab may be preferable to bisphosphonates in myeloma patients in specific scenarios, G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.

Andrew D. Bowser/MDedge News

The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.

The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).

Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).

The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.

Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.

Dr. Roodman reported that he had a consulting or advisory role with Amgen.

CHICAGO – Matched targeted therapy improved long-term survival in patients with advanced cancer, according to findings from a retrospective analysis of molecularly profiled patients.

Of 3,743 patients tested as part of IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy), 1,307 (34.9%) had at least one targetable molecular alteration. Of those, 711 (54.4%) received either matched targeted therapy that was being tested in a clinical trial or – in a small number of cases – therapy with an approved treatment used off label, and 596 (45.6%) received nonmatched therapy, Apostolia-Maria Tsimberidou, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

The objective response rates in 697 evaluable matched therapy patients was 16.2% versus 5.4% in 571 evaluable nonmatched patients, and stable disease for at least 6 months occurred in 18.7% and 14.7% of patients, respectively, for an overall disease control rate of 34.9% versus 20.1%, said Dr. Tsimberidou, a professor at the University of Texas MD Anderson Cancer Center, Houston.

Median progression-free survival in those who received matched versus nonmatched therapy was 4.0 months and 2.8 months, respectively (hazard ratio, 0.67), and median overall survival was 9.3 and 7.3 months, respectively (HR, 0.72), she said.

The 3-year overall survival rate was 15% versus 7%, respectively, and 10-year survival was 6% and 1%, respectively.

Patients included in IMPACT had a mean age of 57 years, and 39% were men. They were heavily pretreated (mean number of prior therapies was 4); only 2.8% of patients had no prior treatment. Cancers included gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%) and lung (8.7%).

In this video interview, Dr. Tsimberidou describes the rationale, methodology, and findings of IMPACT, including the use of a prognostic scoring system developed as part of the study to predict overall survival based on baseline characteristics, such as baseline p13K/AKT/mTOR pathway molecular alterations, which were shown on multivariate analysis in IMPACT to predict shorter overall survival versus other alterations. Other predictors of shorter survival included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age of 60 years or older.

SOURCE: Tsimberidou AM et al. ASCO 2018, Abstract LBA 2553.

CHICAGO – Matched targeted therapy improved long-term survival in patients with advanced cancer, according to findings from a retrospective analysis of molecularly profiled patients.

Of 3,743 patients tested as part of IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy), 1,307 (34.9%) had at least one targetable molecular alteration. Of those, 711 (54.4%) received either matched targeted therapy that was being tested in a clinical trial or – in a small number of cases – therapy with an approved treatment used off label, and 596 (45.6%) received nonmatched therapy, Apostolia-Maria Tsimberidou, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

The objective response rates in 697 evaluable matched therapy patients was 16.2% versus 5.4% in 571 evaluable nonmatched patients, and stable disease for at least 6 months occurred in 18.7% and 14.7% of patients, respectively, for an overall disease control rate of 34.9% versus 20.1%, said Dr. Tsimberidou, a professor at the University of Texas MD Anderson Cancer Center, Houston.

Median progression-free survival in those who received matched versus nonmatched therapy was 4.0 months and 2.8 months, respectively (hazard ratio, 0.67), and median overall survival was 9.3 and 7.3 months, respectively (HR, 0.72), she said.

The 3-year overall survival rate was 15% versus 7%, respectively, and 10-year survival was 6% and 1%, respectively.

Patients included in IMPACT had a mean age of 57 years, and 39% were men. They were heavily pretreated (mean number of prior therapies was 4); only 2.8% of patients had no prior treatment. Cancers included gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%) and lung (8.7%).

In this video interview, Dr. Tsimberidou describes the rationale, methodology, and findings of IMPACT, including the use of a prognostic scoring system developed as part of the study to predict overall survival based on baseline characteristics, such as baseline p13K/AKT/mTOR pathway molecular alterations, which were shown on multivariate analysis in IMPACT to predict shorter overall survival versus other alterations. Other predictors of shorter survival included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age of 60 years or older.

SOURCE: Tsimberidou AM et al. ASCO 2018, Abstract LBA 2553.

CHICAGO – Matched targeted therapy improved long-term survival in patients with advanced cancer, according to findings from a retrospective analysis of molecularly profiled patients.

Of 3,743 patients tested as part of IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy), 1,307 (34.9%) had at least one targetable molecular alteration. Of those, 711 (54.4%) received either matched targeted therapy that was being tested in a clinical trial or – in a small number of cases – therapy with an approved treatment used off label, and 596 (45.6%) received nonmatched therapy, Apostolia-Maria Tsimberidou, MD, reported during a press briefing at the annual meeting of the American Society of Clinical Oncology.

The objective response rates in 697 evaluable matched therapy patients was 16.2% versus 5.4% in 571 evaluable nonmatched patients, and stable disease for at least 6 months occurred in 18.7% and 14.7% of patients, respectively, for an overall disease control rate of 34.9% versus 20.1%, said Dr. Tsimberidou, a professor at the University of Texas MD Anderson Cancer Center, Houston.

Median progression-free survival in those who received matched versus nonmatched therapy was 4.0 months and 2.8 months, respectively (hazard ratio, 0.67), and median overall survival was 9.3 and 7.3 months, respectively (HR, 0.72), she said.

The 3-year overall survival rate was 15% versus 7%, respectively, and 10-year survival was 6% and 1%, respectively.

Patients included in IMPACT had a mean age of 57 years, and 39% were men. They were heavily pretreated (mean number of prior therapies was 4); only 2.8% of patients had no prior treatment. Cancers included gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%) and lung (8.7%).

In this video interview, Dr. Tsimberidou describes the rationale, methodology, and findings of IMPACT, including the use of a prognostic scoring system developed as part of the study to predict overall survival based on baseline characteristics, such as baseline p13K/AKT/mTOR pathway molecular alterations, which were shown on multivariate analysis in IMPACT to predict shorter overall survival versus other alterations. Other predictors of shorter survival included liver metastases, elevated lactate dehydrogenase levels, poor functional status, low albumin levels, elevated platelet counts, and age of 60 years or older.

SOURCE: Tsimberidou AM et al. ASCO 2018, Abstract LBA 2553.

CHICAGO – Pembrolizumab (Keytruda) as first-line treatment of advanced non–small-cell lung cancer (NSCLC) offered longer overall survival with better tolerability compared with chemotherapy, results of the Keynote-042 phase 3 randomized trial show.

Among 1,274 patients with advanced, previously untreated NSCLC with expression of the PD-L1 on 1% or more of tumor cells, median overall survival after a median follow-up of 12.8 months was 16.7 months for patients treated with pembrolizumab monotherapy, compared with 12.1 months for patients treated with either paclitaxel or pemetrexed plus carboplatin, reported lead author Gilberto Lopes, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami.

Neil Osterweil/MDedge News

‘A true milestone’

ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, said at the briefing that “this study represents a true milestone for the field, because now, for the first time, we can say that among non–small-cell lung cancer patients receiving first-line therapy, the vast majority can receive immunotherapy with pembrolizumab instead of chemotherapy.”

He noted that an earlier study, Keynote-024, showed that pembrolizumab significantly improved progression-free survival in patients with tumors expressing PD-L1 on at least 50% of cells compared with standard platinum-based chemotherapy (10.3 vs. 6 months).

Neil Osterweil/MDedge News

As noted before, the primary endpoint of overall survival among all patients with a TPS of 1% or greater was met, with respective median overall survival in the pembrolizumab vs. chemotherapy groups of 16.7 vs. 12.1 months, translating into a hazard ratio favoring pembrolizumab of 0.81 (P = .0018). Respective hazard ratios for the TPS 20% or greater and TPS 50% or greater groups were 0.77 (P = .0020), and 0.69 (P = .0003).

At 12.8 months of median follow-up, 13% of patients assigned to pembrolizumab were still on the drug, and 4.3% of patients were receiving maintenance pemetrexed.

Treatment-related adverse events of any grade occurred in 399 of 636 patients assigned to pembrolizumab (62.7%), vs. 553 of 615 patients assigned to chemotherapy (89.9%).

Grade 3 or greater events occurred in 17.8% vs. 41% of patients, respectively, There were 13 deaths related to therapy in the pembrolizumab arm (2.0%), and 14 in the chemotherapy arm (2.3%).

Adverse events leading to discontinuation were similar between the groups, at 9% and 9.4%, respectively.

There were more immune-mediated adverse events in the pembrolizumab arm (27.8% vs. 7.2%), and of these, grade 3 or greater events occurred in 8% vs. 1.5% of patients, respectively.

There was one immune-mediated death, from pneumonitis, in the immunotherapy arm; there were no deaths related to immune-mediated side effects in the chemotherapy arm.

“I really view this as a ‘double whammy’ for patients,” Dr. Heymach said at the briefing. “Often advances in survival for our lung cancer patients come at the cost of significant toxicities. Here, by contrast, not only are patients living longer and having a much higher likelihood of prolonged survival in years, often instead of months, but they’re also receiving a treatment that has substantially less toxicity across virtually all measures, and this really impacts the day-to-day life of these patients.”

Leena Gandhi, MD, PhD, of the Perlmutter Cancer Center at New York University, the invited discussant at the plenary, agreed that pembrolizumab improves survival, compared with chemotherapy patients with PD-L1 expression levels greater than 1%, but noted that most of the benefit – as also seen in Keynote-024 – was in those patients whose tumors had high levels of PD-L1 expression.

She emphasized that although PD-L1 is an imperfect biomarker, it should still be used to help select patients for therapy, and may be complementary with tumor mutational burden for more precise treatment selection.

“What we know, and what this study adds to, is that PD-L1 really does define a patient population that could receive benefit from pembrolizumab over chemotherapy. Patients with low or no PD-L1 expression likely should get some type of combination therapy,” she said.

“I do think this study extends what we’ve seen from other recent studies, which is that chemotherapy alone is no longer a first-line standard of care in non–small-cell lung cancer,” she added.

Merck funded the study. Dr. Lopes disclosed institutional research funding from Merck Sharp & Dohme, EMD Serono, and AstraZeneca. Dr. Heymach disclosed stock/ownership in Bio-Tree and Cardinal Spine, a consulting or advisory role for Abbvie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, Oncomed, and Synta, and institutional research funding from AstraZeneca. Dr. Gandhi reported having no relevant disclosures.

SOURCE: Lobes G et al. ASCO 2018, abstract LBA4.

CHICAGO – Pembrolizumab (Keytruda) as first-line treatment of advanced non–small-cell lung cancer (NSCLC) offered longer overall survival with better tolerability compared with chemotherapy, results of the Keynote-042 phase 3 randomized trial show.

Among 1,274 patients with advanced, previously untreated NSCLC with expression of the PD-L1 on 1% or more of tumor cells, median overall survival after a median follow-up of 12.8 months was 16.7 months for patients treated with pembrolizumab monotherapy, compared with 12.1 months for patients treated with either paclitaxel or pemetrexed plus carboplatin, reported lead author Gilberto Lopes, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami.

Neil Osterweil/MDedge News

‘A true milestone’

ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, said at the briefing that “this study represents a true milestone for the field, because now, for the first time, we can say that among non–small-cell lung cancer patients receiving first-line therapy, the vast majority can receive immunotherapy with pembrolizumab instead of chemotherapy.”

He noted that an earlier study, Keynote-024, showed that pembrolizumab significantly improved progression-free survival in patients with tumors expressing PD-L1 on at least 50% of cells compared with standard platinum-based chemotherapy (10.3 vs. 6 months).

Neil Osterweil/MDedge News

As noted before, the primary endpoint of overall survival among all patients with a TPS of 1% or greater was met, with respective median overall survival in the pembrolizumab vs. chemotherapy groups of 16.7 vs. 12.1 months, translating into a hazard ratio favoring pembrolizumab of 0.81 (P = .0018). Respective hazard ratios for the TPS 20% or greater and TPS 50% or greater groups were 0.77 (P = .0020), and 0.69 (P = .0003).

At 12.8 months of median follow-up, 13% of patients assigned to pembrolizumab were still on the drug, and 4.3% of patients were receiving maintenance pemetrexed.

Treatment-related adverse events of any grade occurred in 399 of 636 patients assigned to pembrolizumab (62.7%), vs. 553 of 615 patients assigned to chemotherapy (89.9%).

Grade 3 or greater events occurred in 17.8% vs. 41% of patients, respectively, There were 13 deaths related to therapy in the pembrolizumab arm (2.0%), and 14 in the chemotherapy arm (2.3%).

Adverse events leading to discontinuation were similar between the groups, at 9% and 9.4%, respectively.

There were more immune-mediated adverse events in the pembrolizumab arm (27.8% vs. 7.2%), and of these, grade 3 or greater events occurred in 8% vs. 1.5% of patients, respectively.

There was one immune-mediated death, from pneumonitis, in the immunotherapy arm; there were no deaths related to immune-mediated side effects in the chemotherapy arm.

“I really view this as a ‘double whammy’ for patients,” Dr. Heymach said at the briefing. “Often advances in survival for our lung cancer patients come at the cost of significant toxicities. Here, by contrast, not only are patients living longer and having a much higher likelihood of prolonged survival in years, often instead of months, but they’re also receiving a treatment that has substantially less toxicity across virtually all measures, and this really impacts the day-to-day life of these patients.”

Leena Gandhi, MD, PhD, of the Perlmutter Cancer Center at New York University, the invited discussant at the plenary, agreed that pembrolizumab improves survival, compared with chemotherapy patients with PD-L1 expression levels greater than 1%, but noted that most of the benefit – as also seen in Keynote-024 – was in those patients whose tumors had high levels of PD-L1 expression.

She emphasized that although PD-L1 is an imperfect biomarker, it should still be used to help select patients for therapy, and may be complementary with tumor mutational burden for more precise treatment selection.

“What we know, and what this study adds to, is that PD-L1 really does define a patient population that could receive benefit from pembrolizumab over chemotherapy. Patients with low or no PD-L1 expression likely should get some type of combination therapy,” she said.

“I do think this study extends what we’ve seen from other recent studies, which is that chemotherapy alone is no longer a first-line standard of care in non–small-cell lung cancer,” she added.

Merck funded the study. Dr. Lopes disclosed institutional research funding from Merck Sharp & Dohme, EMD Serono, and AstraZeneca. Dr. Heymach disclosed stock/ownership in Bio-Tree and Cardinal Spine, a consulting or advisory role for Abbvie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, Oncomed, and Synta, and institutional research funding from AstraZeneca. Dr. Gandhi reported having no relevant disclosures.

SOURCE: Lobes G et al. ASCO 2018, abstract LBA4.

CHICAGO – Pembrolizumab (Keytruda) as first-line treatment of advanced non–small-cell lung cancer (NSCLC) offered longer overall survival with better tolerability compared with chemotherapy, results of the Keynote-042 phase 3 randomized trial show.

Among 1,274 patients with advanced, previously untreated NSCLC with expression of the PD-L1 on 1% or more of tumor cells, median overall survival after a median follow-up of 12.8 months was 16.7 months for patients treated with pembrolizumab monotherapy, compared with 12.1 months for patients treated with either paclitaxel or pemetrexed plus carboplatin, reported lead author Gilberto Lopes, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami.

Neil Osterweil/MDedge News

‘A true milestone’

ASCO expert John Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, said at the briefing that “this study represents a true milestone for the field, because now, for the first time, we can say that among non–small-cell lung cancer patients receiving first-line therapy, the vast majority can receive immunotherapy with pembrolizumab instead of chemotherapy.”

He noted that an earlier study, Keynote-024, showed that pembrolizumab significantly improved progression-free survival in patients with tumors expressing PD-L1 on at least 50% of cells compared with standard platinum-based chemotherapy (10.3 vs. 6 months).

Neil Osterweil/MDedge News

As noted before, the primary endpoint of overall survival among all patients with a TPS of 1% or greater was met, with respective median overall survival in the pembrolizumab vs. chemotherapy groups of 16.7 vs. 12.1 months, translating into a hazard ratio favoring pembrolizumab of 0.81 (P = .0018). Respective hazard ratios for the TPS 20% or greater and TPS 50% or greater groups were 0.77 (P = .0020), and 0.69 (P = .0003).

At 12.8 months of median follow-up, 13% of patients assigned to pembrolizumab were still on the drug, and 4.3% of patients were receiving maintenance pemetrexed.

Treatment-related adverse events of any grade occurred in 399 of 636 patients assigned to pembrolizumab (62.7%), vs. 553 of 615 patients assigned to chemotherapy (89.9%).

Grade 3 or greater events occurred in 17.8% vs. 41% of patients, respectively, There were 13 deaths related to therapy in the pembrolizumab arm (2.0%), and 14 in the chemotherapy arm (2.3%).

Adverse events leading to discontinuation were similar between the groups, at 9% and 9.4%, respectively.

There were more immune-mediated adverse events in the pembrolizumab arm (27.8% vs. 7.2%), and of these, grade 3 or greater events occurred in 8% vs. 1.5% of patients, respectively.

There was one immune-mediated death, from pneumonitis, in the immunotherapy arm; there were no deaths related to immune-mediated side effects in the chemotherapy arm.

“I really view this as a ‘double whammy’ for patients,” Dr. Heymach said at the briefing. “Often advances in survival for our lung cancer patients come at the cost of significant toxicities. Here, by contrast, not only are patients living longer and having a much higher likelihood of prolonged survival in years, often instead of months, but they’re also receiving a treatment that has substantially less toxicity across virtually all measures, and this really impacts the day-to-day life of these patients.”

Leena Gandhi, MD, PhD, of the Perlmutter Cancer Center at New York University, the invited discussant at the plenary, agreed that pembrolizumab improves survival, compared with chemotherapy patients with PD-L1 expression levels greater than 1%, but noted that most of the benefit – as also seen in Keynote-024 – was in those patients whose tumors had high levels of PD-L1 expression.

She emphasized that although PD-L1 is an imperfect biomarker, it should still be used to help select patients for therapy, and may be complementary with tumor mutational burden for more precise treatment selection.

“What we know, and what this study adds to, is that PD-L1 really does define a patient population that could receive benefit from pembrolizumab over chemotherapy. Patients with low or no PD-L1 expression likely should get some type of combination therapy,” she said.

“I do think this study extends what we’ve seen from other recent studies, which is that chemotherapy alone is no longer a first-line standard of care in non–small-cell lung cancer,” she added.

Merck funded the study. Dr. Lopes disclosed institutional research funding from Merck Sharp & Dohme, EMD Serono, and AstraZeneca. Dr. Heymach disclosed stock/ownership in Bio-Tree and Cardinal Spine, a consulting or advisory role for Abbvie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Genentech, Medivation, Novartis, Oncomed, and Synta, and institutional research funding from AstraZeneca. Dr. Gandhi reported having no relevant disclosures.

SOURCE: Lobes G et al. ASCO 2018, abstract LBA4.

CHICAGO – Is two months of progression-free survival worth it if those months mean living with serious side effects?

Neil Osterweil/ MDedge News

For women with advanced estrogen receptor-positive, HER2-negative breast cancer, the combination of the PI3K inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) bought two additional months of PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half the patients treated with the combination, results of the SANDPIPER trial show.

“These results are positive, but I think we all agree they are modest,” lead investigator José Baselga, MD, PhD from Memorial Sloan Kettering Cancer Center in New York, said at a briefing at the annual meeting of the American Society of Clinical Oncology.

The “challenging tolerability” of the combination led to frequent treatment discontinuations, and may have limited the clinical benefit of the combination, he said, but added that the study serves as proof of principle that PI3K may be a bona fide target in advanced breast cancer.

ASCO expert Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston agreed that PI3K “is a very appealing target. It’s a mutation that probably is the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”

He likened the study findings, however, to a key opening a locked door, only to find that there is a chain latch on the other side preventing entry.

In an interview, Dr. Burstein said that despite the best efforts of Dr. Baselga and others to find a suitable approach to targeting the PI3K pathway, the evidence to date suggests that it may not be an important driver of breast cancer.

Neil Osterweill/ MDedge News

“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.

SOURCE: : Baselga J et al. ASCO 2018 Abstract LBA1006 .

CHICAGO – Is two months of progression-free survival worth it if those months mean living with serious side effects?

Neil Osterweil/ MDedge News

For women with advanced estrogen receptor-positive, HER2-negative breast cancer, the combination of the PI3K inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) bought two additional months of PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half the patients treated with the combination, results of the SANDPIPER trial show.

“These results are positive, but I think we all agree they are modest,” lead investigator José Baselga, MD, PhD from Memorial Sloan Kettering Cancer Center in New York, said at a briefing at the annual meeting of the American Society of Clinical Oncology.

The “challenging tolerability” of the combination led to frequent treatment discontinuations, and may have limited the clinical benefit of the combination, he said, but added that the study serves as proof of principle that PI3K may be a bona fide target in advanced breast cancer.

ASCO expert Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston agreed that PI3K “is a very appealing target. It’s a mutation that probably is the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”

He likened the study findings, however, to a key opening a locked door, only to find that there is a chain latch on the other side preventing entry.

In an interview, Dr. Burstein said that despite the best efforts of Dr. Baselga and others to find a suitable approach to targeting the PI3K pathway, the evidence to date suggests that it may not be an important driver of breast cancer.

Neil Osterweill/ MDedge News

“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.

SOURCE: : Baselga J et al. ASCO 2018 Abstract LBA1006 .

CHICAGO – Is two months of progression-free survival worth it if those months mean living with serious side effects?

Neil Osterweil/ MDedge News

For women with advanced estrogen receptor-positive, HER2-negative breast cancer, the combination of the PI3K inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) bought two additional months of PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half the patients treated with the combination, results of the SANDPIPER trial show.

“These results are positive, but I think we all agree they are modest,” lead investigator José Baselga, MD, PhD from Memorial Sloan Kettering Cancer Center in New York, said at a briefing at the annual meeting of the American Society of Clinical Oncology.

The “challenging tolerability” of the combination led to frequent treatment discontinuations, and may have limited the clinical benefit of the combination, he said, but added that the study serves as proof of principle that PI3K may be a bona fide target in advanced breast cancer.

ASCO expert Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston agreed that PI3K “is a very appealing target. It’s a mutation that probably is the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”

He likened the study findings, however, to a key opening a locked door, only to find that there is a chain latch on the other side preventing entry.

In an interview, Dr. Burstein said that despite the best efforts of Dr. Baselga and others to find a suitable approach to targeting the PI3K pathway, the evidence to date suggests that it may not be an important driver of breast cancer.

Neil Osterweill/ MDedge News

“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.

SOURCE: : Baselga J et al. ASCO 2018 Abstract LBA1006 .

CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.

The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated. The findings represent the first treatment advance for this rare cancer in 30 years.

In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
 

CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.

The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated. The findings represent the first treatment advance for this rare cancer in 30 years.

In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
 

CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.

The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated. The findings represent the first treatment advance for this rare cancer in 30 years.

In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
 

CHICAGO – New data from the TAILORx trial are welcome news for women with HR-positive, HER2-negative, axillary node–negative early-stage breast cancer and their oncologists caught in the gray area surrounding the need for adjuvant chemotherapy.

Results of the noninferiority phase 3 trial—the largest adjuvant breast cancer treatment trial ever conducted—show that among the 6,711 women with an intermediate Oncotype DX Breast Recurrence Score (11-25), those who received only endocrine therapy and skipped adjuvant chemotherapy did not have worse invasive disease-free survival than counterparts who received both (hazard ratio, 1.08; P=.26).

The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy alone and 84.3% with both chemotherapy and endocrine therapy, and the pattern was essentially the same for freedom from any recurrence and distant recurrence, and overall survival.

The findings are practice changing, according to lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice-chair of the ECOG-ACRIN Cancer Research Group.

In a video interview at the annual meeting of the American Society of Clinical Oncology, he discussed implications of the new data for decision making, results of interaction analyses showing that one size does not fit all and certain women with intermediate recurrence scores do derive benefit from adjuvant chemotherapy, as well as plans to use the tumor samples for future analyses on those that do recur.

CHICAGO – New data from the TAILORx trial are welcome news for women with HR-positive, HER2-negative, axillary node–negative early-stage breast cancer and their oncologists caught in the gray area surrounding the need for adjuvant chemotherapy.

Results of the noninferiority phase 3 trial—the largest adjuvant breast cancer treatment trial ever conducted—show that among the 6,711 women with an intermediate Oncotype DX Breast Recurrence Score (11-25), those who received only endocrine therapy and skipped adjuvant chemotherapy did not have worse invasive disease-free survival than counterparts who received both (hazard ratio, 1.08; P=.26).

The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy alone and 84.3% with both chemotherapy and endocrine therapy, and the pattern was essentially the same for freedom from any recurrence and distant recurrence, and overall survival.

The findings are practice changing, according to lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice-chair of the ECOG-ACRIN Cancer Research Group.

In a video interview at the annual meeting of the American Society of Clinical Oncology, he discussed implications of the new data for decision making, results of interaction analyses showing that one size does not fit all and certain women with intermediate recurrence scores do derive benefit from adjuvant chemotherapy, as well as plans to use the tumor samples for future analyses on those that do recur.

CHICAGO – New data from the TAILORx trial are welcome news for women with HR-positive, HER2-negative, axillary node–negative early-stage breast cancer and their oncologists caught in the gray area surrounding the need for adjuvant chemotherapy.

Results of the noninferiority phase 3 trial—the largest adjuvant breast cancer treatment trial ever conducted—show that among the 6,711 women with an intermediate Oncotype DX Breast Recurrence Score (11-25), those who received only endocrine therapy and skipped adjuvant chemotherapy did not have worse invasive disease-free survival than counterparts who received both (hazard ratio, 1.08; P=.26).

The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy alone and 84.3% with both chemotherapy and endocrine therapy, and the pattern was essentially the same for freedom from any recurrence and distant recurrence, and overall survival.

The findings are practice changing, according to lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice-chair of the ECOG-ACRIN Cancer Research Group.

In a video interview at the annual meeting of the American Society of Clinical Oncology, he discussed implications of the new data for decision making, results of interaction analyses showing that one size does not fit all and certain women with intermediate recurrence scores do derive benefit from adjuvant chemotherapy, as well as plans to use the tumor samples for future analyses on those that do recur.