News from the FDA/CDC

The Food and Drug Administration approved olaparib (Lynparza, AstraZeneca) for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

The drug is limited to use in men who have progressed following prior treatment with enzalutamide or abiraterone.

Olaparib becomes the second PARP inhibitor approved by the FDA for use in prostate cancer this week. Earlier, rucaparib (Rubraca, Clovis Oncology) was approved for use in patients with mCRPC that harbor deleterious BRCA mutations (germline and/or somatic).

Olaparib is also indicated for use in ovarian, breast, and pancreatic cancers.

The FDA also approved two companion diagnostic devices for treatment with olaparib: the FoundationOne CDx test (Foundation Medicine) for the selection of patients carrying HRR gene alterations and the BRACAnalysis CDx test (Myriad Genetic Laboratories) for the selection of patients carrying germline BRCA1/2 alterations.

The approval was based on results from the open-label, multicenter PROfound trial, which randomly assigned 387 patients to olaparib 300 mg twice daily and to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a GnRH analogue or had prior bilateral orchiectomy.

The study involved two cohorts. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned in cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned in cohort B (n = 142); those with co-mutations were assigned to cohort A.

The major efficacy outcome of the trial was radiological progression-free survival (rPFS) (cohort A).

In cohort A, patients receiving olaparib had a median rPFS of 7.4 months vs 3.6 months among patients receiving investigator’s choice (hazard ratio [HR], 0.34; P < .0001). Median overall survival was 19.1 months vs 14.7 months (HR, 0.69; P = .0175) and the overall response rate was 33% vs 2% (P < .0001).

In cohort A+B, patients receiving olaparib had a median rPFS of 5.8 months vs 3.5 months among patients receiving investigator’s choice (HR, 0.49; P < .0001).

The study results were first presented at the 2019 annual meeting of the European Society for Medical Oncology. At that time, study investigator Maha Hussain, MD, Northwestern University, Chicago, said the rPFS result and other outcomes were a “remarkable achievement” in such heavily pretreated patients with prostate cancer.

Patients with prostate cancer should now undergo genetic testing of tumor tissue to identify the roughly 30% of patients who can benefit – as is already routinely being done for breast, ovarian, and lung cancer, said experts at ESMO.

The most common adverse reactions with olaparib (≥10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to olaparib, compared with 3.1% of those receiving investigator’s choice of enzalutamide or abiraterone.

Olaparib carries the warning that myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in <1.5% of patients exposed to it as a monotherapy, and that the majority of events had a fatal outcome.

The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.

This article first appeared on Medscape.com.

The Food and Drug Administration approved olaparib (Lynparza, AstraZeneca) for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

The drug is limited to use in men who have progressed following prior treatment with enzalutamide or abiraterone.

Olaparib becomes the second PARP inhibitor approved by the FDA for use in prostate cancer this week. Earlier, rucaparib (Rubraca, Clovis Oncology) was approved for use in patients with mCRPC that harbor deleterious BRCA mutations (germline and/or somatic).

Olaparib is also indicated for use in ovarian, breast, and pancreatic cancers.

The FDA also approved two companion diagnostic devices for treatment with olaparib: the FoundationOne CDx test (Foundation Medicine) for the selection of patients carrying HRR gene alterations and the BRACAnalysis CDx test (Myriad Genetic Laboratories) for the selection of patients carrying germline BRCA1/2 alterations.

The approval was based on results from the open-label, multicenter PROfound trial, which randomly assigned 387 patients to olaparib 300 mg twice daily and to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a GnRH analogue or had prior bilateral orchiectomy.

The study involved two cohorts. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned in cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned in cohort B (n = 142); those with co-mutations were assigned to cohort A.

The major efficacy outcome of the trial was radiological progression-free survival (rPFS) (cohort A).

In cohort A, patients receiving olaparib had a median rPFS of 7.4 months vs 3.6 months among patients receiving investigator’s choice (hazard ratio [HR], 0.34; P < .0001). Median overall survival was 19.1 months vs 14.7 months (HR, 0.69; P = .0175) and the overall response rate was 33% vs 2% (P < .0001).

In cohort A+B, patients receiving olaparib had a median rPFS of 5.8 months vs 3.5 months among patients receiving investigator’s choice (HR, 0.49; P < .0001).

The study results were first presented at the 2019 annual meeting of the European Society for Medical Oncology. At that time, study investigator Maha Hussain, MD, Northwestern University, Chicago, said the rPFS result and other outcomes were a “remarkable achievement” in such heavily pretreated patients with prostate cancer.

Patients with prostate cancer should now undergo genetic testing of tumor tissue to identify the roughly 30% of patients who can benefit – as is already routinely being done for breast, ovarian, and lung cancer, said experts at ESMO.

The most common adverse reactions with olaparib (≥10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to olaparib, compared with 3.1% of those receiving investigator’s choice of enzalutamide or abiraterone.

Olaparib carries the warning that myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in <1.5% of patients exposed to it as a monotherapy, and that the majority of events had a fatal outcome.

The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.

This article first appeared on Medscape.com.

The Food and Drug Administration approved olaparib (Lynparza, AstraZeneca) for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

The drug is limited to use in men who have progressed following prior treatment with enzalutamide or abiraterone.

Olaparib becomes the second PARP inhibitor approved by the FDA for use in prostate cancer this week. Earlier, rucaparib (Rubraca, Clovis Oncology) was approved for use in patients with mCRPC that harbor deleterious BRCA mutations (germline and/or somatic).

Olaparib is also indicated for use in ovarian, breast, and pancreatic cancers.

The FDA also approved two companion diagnostic devices for treatment with olaparib: the FoundationOne CDx test (Foundation Medicine) for the selection of patients carrying HRR gene alterations and the BRACAnalysis CDx test (Myriad Genetic Laboratories) for the selection of patients carrying germline BRCA1/2 alterations.

The approval was based on results from the open-label, multicenter PROfound trial, which randomly assigned 387 patients to olaparib 300 mg twice daily and to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a GnRH analogue or had prior bilateral orchiectomy.

The study involved two cohorts. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned in cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned in cohort B (n = 142); those with co-mutations were assigned to cohort A.

The major efficacy outcome of the trial was radiological progression-free survival (rPFS) (cohort A).

In cohort A, patients receiving olaparib had a median rPFS of 7.4 months vs 3.6 months among patients receiving investigator’s choice (hazard ratio [HR], 0.34; P < .0001). Median overall survival was 19.1 months vs 14.7 months (HR, 0.69; P = .0175) and the overall response rate was 33% vs 2% (P < .0001).

In cohort A+B, patients receiving olaparib had a median rPFS of 5.8 months vs 3.5 months among patients receiving investigator’s choice (HR, 0.49; P < .0001).

The study results were first presented at the 2019 annual meeting of the European Society for Medical Oncology. At that time, study investigator Maha Hussain, MD, Northwestern University, Chicago, said the rPFS result and other outcomes were a “remarkable achievement” in such heavily pretreated patients with prostate cancer.

Patients with prostate cancer should now undergo genetic testing of tumor tissue to identify the roughly 30% of patients who can benefit – as is already routinely being done for breast, ovarian, and lung cancer, said experts at ESMO.

The most common adverse reactions with olaparib (≥10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to olaparib, compared with 3.1% of those receiving investigator’s choice of enzalutamide or abiraterone.

Olaparib carries the warning that myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in <1.5% of patients exposed to it as a monotherapy, and that the majority of events had a fatal outcome.

The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.

This article first appeared on Medscape.com.

In 2019, the number of births in the United States dropped for the fifth consecutive year, as did the fertility rate, and birth rates for women under age 30 fell to record lows, according to the National Center for Health Statistics.

To be exact – at least as exact as is possible from these provisional data – there were 3,745,540 births in the United States last year. That’s down about 1% from 2018 and is the lowest number of births since 1985, Brady E. Hamilton, PhD, and associates at the NCHS said in a rapid release report.

As births go, so goes the general fertility rate. A 2% decrease from 2018 to 2019 left the fertility rate at its lowest point ever: 58.2 births per 1,000 women aged 15-44 years, compared with 59.1 per 1,000 in 2018, the investigators said, based on data from the National Vital Statistics System.

The total fertility rate – defined as “the number of births that a hypothetical group of 1,000 women would have over their lifetimes, based on the age-specific birth rate in a given year” – also reached a record low of 1,705 births per 1,000 women last year after falling 1% from 2018, they reported.

The falling birth rates did not include women over age 35. The birth rate among women aged 40-44 increased by 2% from 2018, as it reached 12.0 births per 1,000 in 2019. “The rate for this age group has risen almost continuously since 1985 by an average of 3% per year,” Dr. Hamilton and associates wrote.

The birth rate for women aged 30-34 years, 98.3 per 1,000, was down 1% from 2018 but was still the highest for any age category. Among younger women, rates all dropped to record lows: 16.6 (ages 15-19), 66.6 (ages 20-24), and 93.7 (ages 25-29), they said.

Preterm birth rates, on the other hand, rose for the fifth year in a row. The rate for 2019, 10.23% of all births, represents an increase of 2% over 2018 and is “the highest level reported in more than a decade,” the investigators noted.

[email protected]

In 2019, the number of births in the United States dropped for the fifth consecutive year, as did the fertility rate, and birth rates for women under age 30 fell to record lows, according to the National Center for Health Statistics.

To be exact – at least as exact as is possible from these provisional data – there were 3,745,540 births in the United States last year. That’s down about 1% from 2018 and is the lowest number of births since 1985, Brady E. Hamilton, PhD, and associates at the NCHS said in a rapid release report.

As births go, so goes the general fertility rate. A 2% decrease from 2018 to 2019 left the fertility rate at its lowest point ever: 58.2 births per 1,000 women aged 15-44 years, compared with 59.1 per 1,000 in 2018, the investigators said, based on data from the National Vital Statistics System.

The total fertility rate – defined as “the number of births that a hypothetical group of 1,000 women would have over their lifetimes, based on the age-specific birth rate in a given year” – also reached a record low of 1,705 births per 1,000 women last year after falling 1% from 2018, they reported.

The falling birth rates did not include women over age 35. The birth rate among women aged 40-44 increased by 2% from 2018, as it reached 12.0 births per 1,000 in 2019. “The rate for this age group has risen almost continuously since 1985 by an average of 3% per year,” Dr. Hamilton and associates wrote.

The birth rate for women aged 30-34 years, 98.3 per 1,000, was down 1% from 2018 but was still the highest for any age category. Among younger women, rates all dropped to record lows: 16.6 (ages 15-19), 66.6 (ages 20-24), and 93.7 (ages 25-29), they said.

Preterm birth rates, on the other hand, rose for the fifth year in a row. The rate for 2019, 10.23% of all births, represents an increase of 2% over 2018 and is “the highest level reported in more than a decade,” the investigators noted.

[email protected]

In 2019, the number of births in the United States dropped for the fifth consecutive year, as did the fertility rate, and birth rates for women under age 30 fell to record lows, according to the National Center for Health Statistics.

To be exact – at least as exact as is possible from these provisional data – there were 3,745,540 births in the United States last year. That’s down about 1% from 2018 and is the lowest number of births since 1985, Brady E. Hamilton, PhD, and associates at the NCHS said in a rapid release report.

As births go, so goes the general fertility rate. A 2% decrease from 2018 to 2019 left the fertility rate at its lowest point ever: 58.2 births per 1,000 women aged 15-44 years, compared with 59.1 per 1,000 in 2018, the investigators said, based on data from the National Vital Statistics System.

The total fertility rate – defined as “the number of births that a hypothetical group of 1,000 women would have over their lifetimes, based on the age-specific birth rate in a given year” – also reached a record low of 1,705 births per 1,000 women last year after falling 1% from 2018, they reported.

The falling birth rates did not include women over age 35. The birth rate among women aged 40-44 increased by 2% from 2018, as it reached 12.0 births per 1,000 in 2019. “The rate for this age group has risen almost continuously since 1985 by an average of 3% per year,” Dr. Hamilton and associates wrote.

The birth rate for women aged 30-34 years, 98.3 per 1,000, was down 1% from 2018 but was still the highest for any age category. Among younger women, rates all dropped to record lows: 16.6 (ages 15-19), 66.6 (ages 20-24), and 93.7 (ages 25-29), they said.

Preterm birth rates, on the other hand, rose for the fifth year in a row. The rate for 2019, 10.23% of all births, represents an increase of 2% over 2018 and is “the highest level reported in more than a decade,” the investigators noted.

[email protected]

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

A completely new approach to the treatment of prostate cancer is now available to clinicians through the approval of the first PARP inhibitor for use in certain patients with this disease.

Rucaparib (Rubraca, Clovis Oncology) is the first PARP inhibitor approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) that harbors deleterious BRCA mutations (germline and/or somatic). The drug is indicated for use in patients who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The drug is already marketed for use in ovarian cancer.

The new prostate cancer indication was granted an accelerated approval by the US Food and Drug Administration (FDA) on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial. A confirmatory phase 3 trial, TRITON3, is currently underway.

“Standard treatment options for men with mCRPC have been limited to androgen receptor–targeting therapies, taxane chemotherapy, radium-223, and sipuleucel-T,” said Wassim Abida, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in a statement.

“Rucaparib is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation,” said Abida, who is also the principal investigator of the TRITON2 study. “Given the level and duration of responses observed with rucaparib in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”
 

Other indications, another PARP inhibitor

Rucaparib is already approved for the treatment of women with advanced BRCA mutation–positive ovarian cancer who have received two or more prior chemotherapies. It is also approved as maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrate a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is awaiting approval for use in prostate cancer in men with BRCA mutations. That pending approval is based on results from the phase 3 PROfound trial, which was hailed as a “landmark trial” when it was presented last year. The results showed a significant improved in disease-free progression. The company recently announced that there was also a significant improvement in overall survival.

Olaparib is already approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status and as first-line maintenance treatment in BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy and for the maintenance treatment of germline BRCA-mutated advanced pancreatic cancer following first-line platinum-based chemotherapy.
 

Details of the TRITON2 study

The accelerated approval for use of rucaparib in BRCA prostate cancer was based on efficacy data from the multicenter, single-arm TRITON2 clinical trial. The cohort included 62 patients with a BRCA (germline and/or somatic) mutation and measurable disease; 115 patients with a BRCA (germline and/or somatic) mutation and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency (HRD)–positive mCRPC.

The major efficacy outcomes were objective response rate (ORR) and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.

For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.

Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 (56%) patients showed a response that lasted 6 months or longer.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%.

The safety evaluation was based on an analysis of the 209 patients with HRD-positive mCRPC and included 115 with deleterious BRCA mutations. The most common adverse events (≥20%; grade 1-4) in the patients with BRCA mutations were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, MDS/AML was not observed in the TRITON2 study, regardless of HRD mutation.
 

Confirmation with TRITON3

A phase 3, randomized, open-label study, TRITON3, is currently underway and is expected to serve as the confirmatory study for the accelerated approval in mCRPC. TRITON3 is comparing rucaparib with physician’s choice of therapy in patients with mCRPC who have specific gene alterations, including BRCA and ATM alterations, and who have experienced disease progression after androgen receptor–directed therapy but have not yet received chemotherapy. The primary endpoint for TRITON3 is radiographic progression-free survival.

This article first appeared on Medscape.com.

A completely new approach to the treatment of prostate cancer is now available to clinicians through the approval of the first PARP inhibitor for use in certain patients with this disease.

Rucaparib (Rubraca, Clovis Oncology) is the first PARP inhibitor approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) that harbors deleterious BRCA mutations (germline and/or somatic). The drug is indicated for use in patients who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The drug is already marketed for use in ovarian cancer.

The new prostate cancer indication was granted an accelerated approval by the US Food and Drug Administration (FDA) on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial. A confirmatory phase 3 trial, TRITON3, is currently underway.

“Standard treatment options for men with mCRPC have been limited to androgen receptor–targeting therapies, taxane chemotherapy, radium-223, and sipuleucel-T,” said Wassim Abida, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in a statement.

“Rucaparib is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation,” said Abida, who is also the principal investigator of the TRITON2 study. “Given the level and duration of responses observed with rucaparib in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”
 

Other indications, another PARP inhibitor

Rucaparib is already approved for the treatment of women with advanced BRCA mutation–positive ovarian cancer who have received two or more prior chemotherapies. It is also approved as maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrate a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is awaiting approval for use in prostate cancer in men with BRCA mutations. That pending approval is based on results from the phase 3 PROfound trial, which was hailed as a “landmark trial” when it was presented last year. The results showed a significant improved in disease-free progression. The company recently announced that there was also a significant improvement in overall survival.

Olaparib is already approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status and as first-line maintenance treatment in BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy and for the maintenance treatment of germline BRCA-mutated advanced pancreatic cancer following first-line platinum-based chemotherapy.
 

Details of the TRITON2 study

The accelerated approval for use of rucaparib in BRCA prostate cancer was based on efficacy data from the multicenter, single-arm TRITON2 clinical trial. The cohort included 62 patients with a BRCA (germline and/or somatic) mutation and measurable disease; 115 patients with a BRCA (germline and/or somatic) mutation and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency (HRD)–positive mCRPC.

The major efficacy outcomes were objective response rate (ORR) and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.

For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.

Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 (56%) patients showed a response that lasted 6 months or longer.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%.

The safety evaluation was based on an analysis of the 209 patients with HRD-positive mCRPC and included 115 with deleterious BRCA mutations. The most common adverse events (≥20%; grade 1-4) in the patients with BRCA mutations were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, MDS/AML was not observed in the TRITON2 study, regardless of HRD mutation.
 

Confirmation with TRITON3

A phase 3, randomized, open-label study, TRITON3, is currently underway and is expected to serve as the confirmatory study for the accelerated approval in mCRPC. TRITON3 is comparing rucaparib with physician’s choice of therapy in patients with mCRPC who have specific gene alterations, including BRCA and ATM alterations, and who have experienced disease progression after androgen receptor–directed therapy but have not yet received chemotherapy. The primary endpoint for TRITON3 is radiographic progression-free survival.

This article first appeared on Medscape.com.

A completely new approach to the treatment of prostate cancer is now available to clinicians through the approval of the first PARP inhibitor for use in certain patients with this disease.

Rucaparib (Rubraca, Clovis Oncology) is the first PARP inhibitor approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) that harbors deleterious BRCA mutations (germline and/or somatic). The drug is indicated for use in patients who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The drug is already marketed for use in ovarian cancer.

The new prostate cancer indication was granted an accelerated approval by the US Food and Drug Administration (FDA) on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial. A confirmatory phase 3 trial, TRITON3, is currently underway.

“Standard treatment options for men with mCRPC have been limited to androgen receptor–targeting therapies, taxane chemotherapy, radium-223, and sipuleucel-T,” said Wassim Abida, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in a statement.

“Rucaparib is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation,” said Abida, who is also the principal investigator of the TRITON2 study. “Given the level and duration of responses observed with rucaparib in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”
 

Other indications, another PARP inhibitor

Rucaparib is already approved for the treatment of women with advanced BRCA mutation–positive ovarian cancer who have received two or more prior chemotherapies. It is also approved as maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrate a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is awaiting approval for use in prostate cancer in men with BRCA mutations. That pending approval is based on results from the phase 3 PROfound trial, which was hailed as a “landmark trial” when it was presented last year. The results showed a significant improved in disease-free progression. The company recently announced that there was also a significant improvement in overall survival.

Olaparib is already approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status and as first-line maintenance treatment in BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy and for the maintenance treatment of germline BRCA-mutated advanced pancreatic cancer following first-line platinum-based chemotherapy.
 

Details of the TRITON2 study

The accelerated approval for use of rucaparib in BRCA prostate cancer was based on efficacy data from the multicenter, single-arm TRITON2 clinical trial. The cohort included 62 patients with a BRCA (germline and/or somatic) mutation and measurable disease; 115 patients with a BRCA (germline and/or somatic) mutation and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency (HRD)–positive mCRPC.

The major efficacy outcomes were objective response rate (ORR) and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.

For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.

Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 (56%) patients showed a response that lasted 6 months or longer.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%.

The safety evaluation was based on an analysis of the 209 patients with HRD-positive mCRPC and included 115 with deleterious BRCA mutations. The most common adverse events (≥20%; grade 1-4) in the patients with BRCA mutations were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, MDS/AML was not observed in the TRITON2 study, regardless of HRD mutation.
 

Confirmation with TRITON3

A phase 3, randomized, open-label study, TRITON3, is currently underway and is expected to serve as the confirmatory study for the accelerated approval in mCRPC. TRITON3 is comparing rucaparib with physician’s choice of therapy in patients with mCRPC who have specific gene alterations, including BRCA and ATM alterations, and who have experienced disease progression after androgen receptor–directed therapy but have not yet received chemotherapy. The primary endpoint for TRITON3 is radiographic progression-free survival.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved ripretinib (Qinlock, Deciphera Pharmaceuticals) tablets as the first-ever drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumors (GISTs).

A new kinase inhibitor, ripretinib is indicated for patients previously treated with three or more other kinase inhibitor therapies, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST … some patients don’t respond to treatment and their tumors continue to progress. Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Dr. Pazdur explained that the FDA has previously approved four targeted therapies for GISTs – imatinib in 2002, sunitinib in 2006, regorafenib in 2013, and avapritinib in 2020.

The new approval of ripretinib is based on the results of a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GISTs whose disease progressed despite prior treatment with the other targeted therapies.

In the trial, patients received ripretinib or placebo once a day in 28-day cycles, until disease progression, or intolerable toxicity.

Median progression-free survival was 6.3 months in the ripretinib arm versus 1 month in the placebo arm.

The most common side effects with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Ripretinib also can cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.

The FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of this application as part of Project Orbis.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved ripretinib (Qinlock, Deciphera Pharmaceuticals) tablets as the first-ever drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumors (GISTs).

A new kinase inhibitor, ripretinib is indicated for patients previously treated with three or more other kinase inhibitor therapies, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST … some patients don’t respond to treatment and their tumors continue to progress. Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Dr. Pazdur explained that the FDA has previously approved four targeted therapies for GISTs – imatinib in 2002, sunitinib in 2006, regorafenib in 2013, and avapritinib in 2020.

The new approval of ripretinib is based on the results of a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GISTs whose disease progressed despite prior treatment with the other targeted therapies.

In the trial, patients received ripretinib or placebo once a day in 28-day cycles, until disease progression, or intolerable toxicity.

Median progression-free survival was 6.3 months in the ripretinib arm versus 1 month in the placebo arm.

The most common side effects with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Ripretinib also can cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.

The FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of this application as part of Project Orbis.

This article first appeared on Medscape.com.

The U.S. Food and Drug Administration approved ripretinib (Qinlock, Deciphera Pharmaceuticals) tablets as the first-ever drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumors (GISTs).

A new kinase inhibitor, ripretinib is indicated for patients previously treated with three or more other kinase inhibitor therapies, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST … some patients don’t respond to treatment and their tumors continue to progress. Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Dr. Pazdur explained that the FDA has previously approved four targeted therapies for GISTs – imatinib in 2002, sunitinib in 2006, regorafenib in 2013, and avapritinib in 2020.

The new approval of ripretinib is based on the results of a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 129 patients with advanced GISTs whose disease progressed despite prior treatment with the other targeted therapies.

In the trial, patients received ripretinib or placebo once a day in 28-day cycles, until disease progression, or intolerable toxicity.

Median progression-free survival was 6.3 months in the ripretinib arm versus 1 month in the placebo arm.

The most common side effects with ripretinib were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, and vomiting.

Ripretinib also can cause skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.

The FDA collaborated with the Australian Therapeutic Goods Administration and Health Canada on the review of this application as part of Project Orbis.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to pomalidomide (Pomalyst, Bristol-Myers Squibb) for the treatment of AIDS-related Kaposi sarcoma that is resistant to highly active antiretroviral therapy (HAART) or that occurs in HIV-negative patients.

Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company.

The drug, a thalidomide analogue, is already marketed for the treatment of multiple myeloma.

Pomalidomide has “shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch, National Cancer Institute, in a press statement.

The conditional approval is based on the 71% overall response rate observed in a phase 1/2 open-label, single-arm clinical trial that involved 28 patients, 18 of whom were HIV positive and 10 of whom were HIV negative.

Most of the responses were partial (57%; 16/28); 14% (4/28) were complete. Median duration of response was 12.1 months. Additionally, for half of the patients who showed a response, that response was maintained for more than 12 months.

Patients received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity occurred.

Permanent discontinuation because of an adverse reaction occurred in 11% (3/28) of patients.

Adverse reactions (≥20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%).

Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%).

Grade 3 or 4 laboratory abnormalities (≥5%) that worsened from baseline included decreased absolute neutrophil count (50%), decreased phosphate level (25%), elevated glucose level (7%), and elevated creatine kinase level (7%).

As a thalidomide analogue, pomalidomide includes a boxed warning in the prescribing information; thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. Deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur in patients treated with pomalidomide; thromboprophylaxis is recommended.

Pomalidomide is available only through a restricted distribution program, Pomalyst REMS.

This article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to pomalidomide (Pomalyst, Bristol-Myers Squibb) for the treatment of AIDS-related Kaposi sarcoma that is resistant to highly active antiretroviral therapy (HAART) or that occurs in HIV-negative patients.

Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company.

The drug, a thalidomide analogue, is already marketed for the treatment of multiple myeloma.

Pomalidomide has “shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch, National Cancer Institute, in a press statement.

The conditional approval is based on the 71% overall response rate observed in a phase 1/2 open-label, single-arm clinical trial that involved 28 patients, 18 of whom were HIV positive and 10 of whom were HIV negative.

Most of the responses were partial (57%; 16/28); 14% (4/28) were complete. Median duration of response was 12.1 months. Additionally, for half of the patients who showed a response, that response was maintained for more than 12 months.

Patients received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity occurred.

Permanent discontinuation because of an adverse reaction occurred in 11% (3/28) of patients.

Adverse reactions (≥20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%).

Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%).

Grade 3 or 4 laboratory abnormalities (≥5%) that worsened from baseline included decreased absolute neutrophil count (50%), decreased phosphate level (25%), elevated glucose level (7%), and elevated creatine kinase level (7%).

As a thalidomide analogue, pomalidomide includes a boxed warning in the prescribing information; thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. Deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur in patients treated with pomalidomide; thromboprophylaxis is recommended.

Pomalidomide is available only through a restricted distribution program, Pomalyst REMS.

This article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to pomalidomide (Pomalyst, Bristol-Myers Squibb) for the treatment of AIDS-related Kaposi sarcoma that is resistant to highly active antiretroviral therapy (HAART) or that occurs in HIV-negative patients.

Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company.

The drug, a thalidomide analogue, is already marketed for the treatment of multiple myeloma.

Pomalidomide has “shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch, National Cancer Institute, in a press statement.

The conditional approval is based on the 71% overall response rate observed in a phase 1/2 open-label, single-arm clinical trial that involved 28 patients, 18 of whom were HIV positive and 10 of whom were HIV negative.

Most of the responses were partial (57%; 16/28); 14% (4/28) were complete. Median duration of response was 12.1 months. Additionally, for half of the patients who showed a response, that response was maintained for more than 12 months.

Patients received 5 mg of pomalidomide once daily for 21 of 28-day cycles until disease progression or unacceptable toxicity occurred.

Permanent discontinuation because of an adverse reaction occurred in 11% (3/28) of patients.

Adverse reactions (≥20%) included maculopapular rash (71%), constipation (71%), fatigue (68%), nausea (36%), diarrhea (32%), cough (29%), dyspnea (29%), peripheral edema (29%), upper respiratory tract infection (29%), muscle spasms (25%), hypothyroidism (21%), dry skin (21%), and chills (21%).

Grade 3 or 4 adverse reactions included maculopapular rash (3.6%), diarrhea (3.6%), and peripheral edema (3.6%).

Grade 3 or 4 laboratory abnormalities (≥5%) that worsened from baseline included decreased absolute neutrophil count (50%), decreased phosphate level (25%), elevated glucose level (7%), and elevated creatine kinase level (7%).

As a thalidomide analogue, pomalidomide includes a boxed warning in the prescribing information; thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. Deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke can occur in patients treated with pomalidomide; thromboprophylaxis is recommended.

Pomalidomide is available only through a restricted distribution program, Pomalyst REMS.

This article first appeared on Medscape.com.

The social distancing and sheltering in place mandated because of the COVID-19 pandemic are keeping parents and kids out of their doctors’ offices, and that has prompted a steep decline in recommended routine vaccinations for U.S. children, according to Centers for Disease Control and Prevention researchers.

Pediatric vaccinations dropped sharply after the national emergency was declared on March 13, suggesting that some children may be at increased risk for other serious infectious diseases, such as measles.

The researchers compared weekly orders for federally funded vaccines from Jan. 6 to April 19, 2020, with those during the same period in 2019.

They noted that, by the end of the study period, there was a cumulative COVID-19–related decline of 2.5 million doses in orders for routine noninfluenza pediatric childhood vaccines recommended by the Advisory Committee on Immunization Practices, as well as a cumulative decline in orders of 250,000 doses of measles vaccines.

Although the overall decrease in vaccinations during the study period was larger, according to CDC spokesperson Richard Quartarone, the above figures represent declines clearly associated with the pandemic.

The weekly number of measles vaccines ordered for children aged 24 months or older fell dramatically to about 500 during the week beginning March 16, 2020, and fell further to approximately 250 during the week beginning March 23. It stayed at that level until the week beginning April 13. By comparison, more than 2,500 were ordered during the week starting March 2, before the emergency was declared.

The decline was notably less for children younger than 2 years. For those children, orders dropped to about 750 during the week starting March 23 and climbed slightly for 3 weeks. By comparison, during the week of March 2, about 2,000 vaccines were ordered.

The findings, which were published in the CDC’s Morbidity and Mortality Weekly Report, stem from an analysis of ordering data from the federal Vaccines for Children (VFC) Program, as well as from vaccine administration data from the CDC’s Vaccine Tracking System and the collaborative Vaccine Safety Datalink (VSD).

The VFC provides federally purchased vaccines at no cost to about half of persons aged 18 years or younger. The VSD collaborates on vaccine coverage with the CDC’s Immunization Safety Office and eight large health care organizations across the country. Vaccination coverage is the usual metric for assessing vaccine usage; providers’ orders and the number of doses administered are two proxy measures, the authors explained.

“The substantial reduction in VFC-funded pediatric vaccine ordering after the COVID-19 emergency declaration is consistent with changes in vaccine administration among children in the VSD population receiving care through eight large U.S. health care organizations,” wrote Jeanne M. Santoli, MD, and colleagues, of the immunization services division at the National Center for Immunization and Respiratory Diseases. “The smaller decline in measles-containing vaccine administration among children aged ≤24 months suggests that system-level strategies to prioritize well child care and immunization for this age group are being implemented.”

Dr. Santoli, who is an Atlanta-based pediatrician, and associates stressed the importance of maintaining regular vaccinations during the pandemic. “The identified declines in routine pediatric vaccine ordering and doses administered might indicate that U.S. children and their communities face increased risks for outbreaks of vaccine-preventable diseases,” they wrote. “Parental concerns about potentially exposing their children to COVID-19 during well child visits might contribute to the declines observed.” Parents should therefore be reminded of the necessity of protecting their children against vaccine-preventable diseases.

In 2019, a Gallup survey reported that overall support for vaccination continued to decline in the United States.

The researchers predicted that, as social distancing relaxes, unvaccinated children will be more susceptible to other serious diseases. “In response, continued coordinated efforts between health care providers and public health officials at the local, state, and federal levels will be necessary to achieve rapid catch-up vaccination,” they concluded.

The authors disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The social distancing and sheltering in place mandated because of the COVID-19 pandemic are keeping parents and kids out of their doctors’ offices, and that has prompted a steep decline in recommended routine vaccinations for U.S. children, according to Centers for Disease Control and Prevention researchers.

Pediatric vaccinations dropped sharply after the national emergency was declared on March 13, suggesting that some children may be at increased risk for other serious infectious diseases, such as measles.

The researchers compared weekly orders for federally funded vaccines from Jan. 6 to April 19, 2020, with those during the same period in 2019.

They noted that, by the end of the study period, there was a cumulative COVID-19–related decline of 2.5 million doses in orders for routine noninfluenza pediatric childhood vaccines recommended by the Advisory Committee on Immunization Practices, as well as a cumulative decline in orders of 250,000 doses of measles vaccines.

Although the overall decrease in vaccinations during the study period was larger, according to CDC spokesperson Richard Quartarone, the above figures represent declines clearly associated with the pandemic.

The weekly number of measles vaccines ordered for children aged 24 months or older fell dramatically to about 500 during the week beginning March 16, 2020, and fell further to approximately 250 during the week beginning March 23. It stayed at that level until the week beginning April 13. By comparison, more than 2,500 were ordered during the week starting March 2, before the emergency was declared.

The decline was notably less for children younger than 2 years. For those children, orders dropped to about 750 during the week starting March 23 and climbed slightly for 3 weeks. By comparison, during the week of March 2, about 2,000 vaccines were ordered.

The findings, which were published in the CDC’s Morbidity and Mortality Weekly Report, stem from an analysis of ordering data from the federal Vaccines for Children (VFC) Program, as well as from vaccine administration data from the CDC’s Vaccine Tracking System and the collaborative Vaccine Safety Datalink (VSD).

The VFC provides federally purchased vaccines at no cost to about half of persons aged 18 years or younger. The VSD collaborates on vaccine coverage with the CDC’s Immunization Safety Office and eight large health care organizations across the country. Vaccination coverage is the usual metric for assessing vaccine usage; providers’ orders and the number of doses administered are two proxy measures, the authors explained.

“The substantial reduction in VFC-funded pediatric vaccine ordering after the COVID-19 emergency declaration is consistent with changes in vaccine administration among children in the VSD population receiving care through eight large U.S. health care organizations,” wrote Jeanne M. Santoli, MD, and colleagues, of the immunization services division at the National Center for Immunization and Respiratory Diseases. “The smaller decline in measles-containing vaccine administration among children aged ≤24 months suggests that system-level strategies to prioritize well child care and immunization for this age group are being implemented.”

Dr. Santoli, who is an Atlanta-based pediatrician, and associates stressed the importance of maintaining regular vaccinations during the pandemic. “The identified declines in routine pediatric vaccine ordering and doses administered might indicate that U.S. children and their communities face increased risks for outbreaks of vaccine-preventable diseases,” they wrote. “Parental concerns about potentially exposing their children to COVID-19 during well child visits might contribute to the declines observed.” Parents should therefore be reminded of the necessity of protecting their children against vaccine-preventable diseases.

In 2019, a Gallup survey reported that overall support for vaccination continued to decline in the United States.

The researchers predicted that, as social distancing relaxes, unvaccinated children will be more susceptible to other serious diseases. “In response, continued coordinated efforts between health care providers and public health officials at the local, state, and federal levels will be necessary to achieve rapid catch-up vaccination,” they concluded.

The authors disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The social distancing and sheltering in place mandated because of the COVID-19 pandemic are keeping parents and kids out of their doctors’ offices, and that has prompted a steep decline in recommended routine vaccinations for U.S. children, according to Centers for Disease Control and Prevention researchers.

Pediatric vaccinations dropped sharply after the national emergency was declared on March 13, suggesting that some children may be at increased risk for other serious infectious diseases, such as measles.

The researchers compared weekly orders for federally funded vaccines from Jan. 6 to April 19, 2020, with those during the same period in 2019.

They noted that, by the end of the study period, there was a cumulative COVID-19–related decline of 2.5 million doses in orders for routine noninfluenza pediatric childhood vaccines recommended by the Advisory Committee on Immunization Practices, as well as a cumulative decline in orders of 250,000 doses of measles vaccines.

Although the overall decrease in vaccinations during the study period was larger, according to CDC spokesperson Richard Quartarone, the above figures represent declines clearly associated with the pandemic.

The weekly number of measles vaccines ordered for children aged 24 months or older fell dramatically to about 500 during the week beginning March 16, 2020, and fell further to approximately 250 during the week beginning March 23. It stayed at that level until the week beginning April 13. By comparison, more than 2,500 were ordered during the week starting March 2, before the emergency was declared.

The decline was notably less for children younger than 2 years. For those children, orders dropped to about 750 during the week starting March 23 and climbed slightly for 3 weeks. By comparison, during the week of March 2, about 2,000 vaccines were ordered.

The findings, which were published in the CDC’s Morbidity and Mortality Weekly Report, stem from an analysis of ordering data from the federal Vaccines for Children (VFC) Program, as well as from vaccine administration data from the CDC’s Vaccine Tracking System and the collaborative Vaccine Safety Datalink (VSD).

The VFC provides federally purchased vaccines at no cost to about half of persons aged 18 years or younger. The VSD collaborates on vaccine coverage with the CDC’s Immunization Safety Office and eight large health care organizations across the country. Vaccination coverage is the usual metric for assessing vaccine usage; providers’ orders and the number of doses administered are two proxy measures, the authors explained.

“The substantial reduction in VFC-funded pediatric vaccine ordering after the COVID-19 emergency declaration is consistent with changes in vaccine administration among children in the VSD population receiving care through eight large U.S. health care organizations,” wrote Jeanne M. Santoli, MD, and colleagues, of the immunization services division at the National Center for Immunization and Respiratory Diseases. “The smaller decline in measles-containing vaccine administration among children aged ≤24 months suggests that system-level strategies to prioritize well child care and immunization for this age group are being implemented.”

Dr. Santoli, who is an Atlanta-based pediatrician, and associates stressed the importance of maintaining regular vaccinations during the pandemic. “The identified declines in routine pediatric vaccine ordering and doses administered might indicate that U.S. children and their communities face increased risks for outbreaks of vaccine-preventable diseases,” they wrote. “Parental concerns about potentially exposing their children to COVID-19 during well child visits might contribute to the declines observed.” Parents should therefore be reminded of the necessity of protecting their children against vaccine-preventable diseases.

In 2019, a Gallup survey reported that overall support for vaccination continued to decline in the United States.

The researchers predicted that, as social distancing relaxes, unvaccinated children will be more susceptible to other serious diseases. “In response, continued coordinated efforts between health care providers and public health officials at the local, state, and federal levels will be necessary to achieve rapid catch-up vaccination,” they concluded.

The authors disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration has announced a new approved indication for olaparib (Lynparza) in adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Olaparib is now FDA-approved for use in combination with bevacizumab as maintenance therapy in patients who responded to first-line platinum-based chemotherapy and whose cancer is homologous recombination deficiency positive, as defined by a deleterious or suspected deleterious BRCA mutation and/or genomic instability.

The FDA also approved the Myriad myChoice CDx test as a companion diagnostic for olaparib.

Trial results

The efficacy of olaparib and the myChoice CDx test were assessed in patients in the phase 3 PAOLA-1 trial (NCT02477644). The study enrolled patients with advanced high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received first-line platinum-based chemotherapy and bevacizumab.

Patients were stratified by first-line treatment outcome and BRCA mutation status, as determined by prospective local testing. All available clinical samples were retrospectively tested with the Myriad myChoice CDx test.

The patients were randomized to receive olaparib at 300 mg orally twice daily in combination with bevacizumab at 15 mg/kg every 3 weeks (n = 537) or placebo plus bevacizumab (n = 269). Patients continued bevacizumab in the maintenance setting and started olaparib 3-9 weeks after their last chemotherapy dose. Olaparib could be continued for up to 2 years or until disease progression or unacceptable toxicity.

The median progression-free survival among the 387 patients with homologous recombination deficiency-positive tumors was 37.2 months in the olaparib arm and 17.7 months in the placebo arm (hazard ratio, 0.33), according to the prescribing information for olaparib.

Serious adverse events occurred in 31% of patients in the olaparib arm. The most common were hypertension (19%) and anemia (17%).

Dose interruptions from adverse events occurred in 54% of patients in the olaparib arm, and dose reductions from adverse events occurred in 41%.

[email protected]

The Food and Drug Administration has announced a new approved indication for olaparib (Lynparza) in adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Olaparib is now FDA-approved for use in combination with bevacizumab as maintenance therapy in patients who responded to first-line platinum-based chemotherapy and whose cancer is homologous recombination deficiency positive, as defined by a deleterious or suspected deleterious BRCA mutation and/or genomic instability.

The FDA also approved the Myriad myChoice CDx test as a companion diagnostic for olaparib.

Trial results

The efficacy of olaparib and the myChoice CDx test were assessed in patients in the phase 3 PAOLA-1 trial (NCT02477644). The study enrolled patients with advanced high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received first-line platinum-based chemotherapy and bevacizumab.

Patients were stratified by first-line treatment outcome and BRCA mutation status, as determined by prospective local testing. All available clinical samples were retrospectively tested with the Myriad myChoice CDx test.

The patients were randomized to receive olaparib at 300 mg orally twice daily in combination with bevacizumab at 15 mg/kg every 3 weeks (n = 537) or placebo plus bevacizumab (n = 269). Patients continued bevacizumab in the maintenance setting and started olaparib 3-9 weeks after their last chemotherapy dose. Olaparib could be continued for up to 2 years or until disease progression or unacceptable toxicity.

The median progression-free survival among the 387 patients with homologous recombination deficiency-positive tumors was 37.2 months in the olaparib arm and 17.7 months in the placebo arm (hazard ratio, 0.33), according to the prescribing information for olaparib.

Serious adverse events occurred in 31% of patients in the olaparib arm. The most common were hypertension (19%) and anemia (17%).

Dose interruptions from adverse events occurred in 54% of patients in the olaparib arm, and dose reductions from adverse events occurred in 41%.

[email protected]

The Food and Drug Administration has announced a new approved indication for olaparib (Lynparza) in adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Olaparib is now FDA-approved for use in combination with bevacizumab as maintenance therapy in patients who responded to first-line platinum-based chemotherapy and whose cancer is homologous recombination deficiency positive, as defined by a deleterious or suspected deleterious BRCA mutation and/or genomic instability.

The FDA also approved the Myriad myChoice CDx test as a companion diagnostic for olaparib.

Trial results

The efficacy of olaparib and the myChoice CDx test were assessed in patients in the phase 3 PAOLA-1 trial (NCT02477644). The study enrolled patients with advanced high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received first-line platinum-based chemotherapy and bevacizumab.

Patients were stratified by first-line treatment outcome and BRCA mutation status, as determined by prospective local testing. All available clinical samples were retrospectively tested with the Myriad myChoice CDx test.

The patients were randomized to receive olaparib at 300 mg orally twice daily in combination with bevacizumab at 15 mg/kg every 3 weeks (n = 537) or placebo plus bevacizumab (n = 269). Patients continued bevacizumab in the maintenance setting and started olaparib 3-9 weeks after their last chemotherapy dose. Olaparib could be continued for up to 2 years or until disease progression or unacceptable toxicity.

The median progression-free survival among the 387 patients with homologous recombination deficiency-positive tumors was 37.2 months in the olaparib arm and 17.7 months in the placebo arm (hazard ratio, 0.33), according to the prescribing information for olaparib.

Serious adverse events occurred in 31% of patients in the olaparib arm. The most common were hypertension (19%) and anemia (17%).

Dose interruptions from adverse events occurred in 54% of patients in the olaparib arm, and dose reductions from adverse events occurred in 41%.

[email protected]

Selpercatinib (Retevmo) becomes the first targeted therapy to be approved by the US Food and Drug Administration (FDA) for use in patients with cancer who have certain tumors that have an alteration (mutation or fusion) in the RET gene.

The drug is indicated for use in RET-positive tumors found in the following:

• Non–small cell lung cancer (NSCLC) that has spread in adult patients
• Advanced medullary thyroid cancer (MTC) or MTC that has spread in adult and pediatric patients (older than 12 years) who require systemic therapy
• Thyroid cancer that requires systemic therapy and that has stopped responding to or is not appropriate for radioactive iodine therapy in adult and pediatric (older than 12 years) patients.

Before initiating treatment, a RET gene alteration must be determined via laboratory testing, the FDA emphasized. However, no FDA-approved test is currently available for detecting RET fusions/mutations.
 

Approval based on responses in open-label trial

This was an accelerated approval based on the overall response rate (ORR) and duration of response (DOR) seen in an open-label clinical trial (the phase 1/2 LIBRETTO-001 study), which involved patients with each of the three types of tumors.

All patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

For this trial, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using next-generation sequencing, polymerase chain reaction testing, or fluorescence in situ hybridization, according to Eli Lilly, the company marketing selpercatinib. Immunohistochemistry was not used in the clinical trial.

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%.

Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had not received any previous treatment. The ORR for these patients was 84%.

For both groups, among patients who responded to treatment, the response lasted more than 6 months.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases,” LIBRETTO-001 lead investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York, N.Y., said in an Eli Lilly press release.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy,” Dr. Drilon added.

About 1% to 2% of NSCLC tumors are thought to have a RET alteration.

The same trial also included patients with thyroid cancer.

Efficacy for MTC was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The ORR in these patients was 69%.

In addition, selpercatinib was evaluated in 88 patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for these patients was 73%.

The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment. The ORR was 79%. Eight patients had received only RAI. The ORR for these patients was 100%.

In all the cases of thyroid cancer and lung cancer, among the patients who responded to treatment, the response lasted longer than 6 months.

“RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers,” Lori J. Wirth, MD, of Massachusetts General Hospital Cancer Center in Boston, noted in the company release.

A fact sheet from Eli Lilly notes that RET mutations are found in about 60% of sporadic MTC cases and in over 90% of familial MTC cases, and that RET fusions are found in approximately 10% to 20% of papillary thyroid cancers.

“For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET,” Dr. Wirth commented. “Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option.”

In the LIBRETTO-001 trial, the rate of discontinuations because of adverse reactions (ARs) was 5%, the company reported. The most common ARs, including laboratory abnormalities (≥25%), were increased aspartate aminotransferase level, increased alanine aminotransferase level, increased glucose level, decreased leukocyte count, decreased albumin level, decreased calcium level, dry mouth, diarrhea, increased creatinine level, increased alkaline phosphatase level, hypertension, fatigue, edema, decreased platelet count, increased total cholesterol level, rash, decreased sodium levels, and constipation. The most frequent serious AR (≥2%) was pneumonia.

The FDA warned that selpercatinib can cause hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions. It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women.

Selpercatinib is currently being assessed in two phase 3 confirmatory trials. LIBRETTO-431 will test the drug in previously untreated patients with RET-positive NSCLC. LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

The company that developed selpercaptinib, Loxo Oncology, was acquired by Eli Lilly last year in an $8 billion takeover. This drug was billed as the most promising asset in that deal, alongside oral BTK inhibitor LOXO-305, according to a report in Pharmaphorum.

Loxo developed Vitrakvi (larotrectinib), the first TRK inhibitor to reach the market, as well as the follow-up drug LOXO-195. Both were acquired by Bayer ahead of the Lilly takeover, that report notes.

This article first appeared on Medscape.com.

Selpercatinib (Retevmo) becomes the first targeted therapy to be approved by the US Food and Drug Administration (FDA) for use in patients with cancer who have certain tumors that have an alteration (mutation or fusion) in the RET gene.

The drug is indicated for use in RET-positive tumors found in the following:

• Non–small cell lung cancer (NSCLC) that has spread in adult patients
• Advanced medullary thyroid cancer (MTC) or MTC that has spread in adult and pediatric patients (older than 12 years) who require systemic therapy
• Thyroid cancer that requires systemic therapy and that has stopped responding to or is not appropriate for radioactive iodine therapy in adult and pediatric (older than 12 years) patients.

Before initiating treatment, a RET gene alteration must be determined via laboratory testing, the FDA emphasized. However, no FDA-approved test is currently available for detecting RET fusions/mutations.
 

Approval based on responses in open-label trial

This was an accelerated approval based on the overall response rate (ORR) and duration of response (DOR) seen in an open-label clinical trial (the phase 1/2 LIBRETTO-001 study), which involved patients with each of the three types of tumors.

All patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

For this trial, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using next-generation sequencing, polymerase chain reaction testing, or fluorescence in situ hybridization, according to Eli Lilly, the company marketing selpercatinib. Immunohistochemistry was not used in the clinical trial.

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%.

Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had not received any previous treatment. The ORR for these patients was 84%.

For both groups, among patients who responded to treatment, the response lasted more than 6 months.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases,” LIBRETTO-001 lead investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York, N.Y., said in an Eli Lilly press release.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy,” Dr. Drilon added.

About 1% to 2% of NSCLC tumors are thought to have a RET alteration.

The same trial also included patients with thyroid cancer.

Efficacy for MTC was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The ORR in these patients was 69%.

In addition, selpercatinib was evaluated in 88 patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for these patients was 73%.

The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment. The ORR was 79%. Eight patients had received only RAI. The ORR for these patients was 100%.

In all the cases of thyroid cancer and lung cancer, among the patients who responded to treatment, the response lasted longer than 6 months.

“RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers,” Lori J. Wirth, MD, of Massachusetts General Hospital Cancer Center in Boston, noted in the company release.

A fact sheet from Eli Lilly notes that RET mutations are found in about 60% of sporadic MTC cases and in over 90% of familial MTC cases, and that RET fusions are found in approximately 10% to 20% of papillary thyroid cancers.

“For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET,” Dr. Wirth commented. “Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option.”

In the LIBRETTO-001 trial, the rate of discontinuations because of adverse reactions (ARs) was 5%, the company reported. The most common ARs, including laboratory abnormalities (≥25%), were increased aspartate aminotransferase level, increased alanine aminotransferase level, increased glucose level, decreased leukocyte count, decreased albumin level, decreased calcium level, dry mouth, diarrhea, increased creatinine level, increased alkaline phosphatase level, hypertension, fatigue, edema, decreased platelet count, increased total cholesterol level, rash, decreased sodium levels, and constipation. The most frequent serious AR (≥2%) was pneumonia.

The FDA warned that selpercatinib can cause hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions. It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women.

Selpercatinib is currently being assessed in two phase 3 confirmatory trials. LIBRETTO-431 will test the drug in previously untreated patients with RET-positive NSCLC. LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

The company that developed selpercaptinib, Loxo Oncology, was acquired by Eli Lilly last year in an $8 billion takeover. This drug was billed as the most promising asset in that deal, alongside oral BTK inhibitor LOXO-305, according to a report in Pharmaphorum.

Loxo developed Vitrakvi (larotrectinib), the first TRK inhibitor to reach the market, as well as the follow-up drug LOXO-195. Both were acquired by Bayer ahead of the Lilly takeover, that report notes.

This article first appeared on Medscape.com.

Selpercatinib (Retevmo) becomes the first targeted therapy to be approved by the US Food and Drug Administration (FDA) for use in patients with cancer who have certain tumors that have an alteration (mutation or fusion) in the RET gene.

The drug is indicated for use in RET-positive tumors found in the following:

• Non–small cell lung cancer (NSCLC) that has spread in adult patients
• Advanced medullary thyroid cancer (MTC) or MTC that has spread in adult and pediatric patients (older than 12 years) who require systemic therapy
• Thyroid cancer that requires systemic therapy and that has stopped responding to or is not appropriate for radioactive iodine therapy in adult and pediatric (older than 12 years) patients.

Before initiating treatment, a RET gene alteration must be determined via laboratory testing, the FDA emphasized. However, no FDA-approved test is currently available for detecting RET fusions/mutations.
 

Approval based on responses in open-label trial

This was an accelerated approval based on the overall response rate (ORR) and duration of response (DOR) seen in an open-label clinical trial (the phase 1/2 LIBRETTO-001 study), which involved patients with each of the three types of tumors.

All patients received selpercatinib 160 mg orally twice daily until disease progression or unacceptable toxicity occurred.

For this trial, identification of a RET gene alteration was prospectively determined in plasma or tumor tissue by local laboratories using next-generation sequencing, polymerase chain reaction testing, or fluorescence in situ hybridization, according to Eli Lilly, the company marketing selpercatinib. Immunohistochemistry was not used in the clinical trial.

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%.

Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had not received any previous treatment. The ORR for these patients was 84%.

For both groups, among patients who responded to treatment, the response lasted more than 6 months.

“In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases,” LIBRETTO-001 lead investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center in New York, N.Y., said in an Eli Lilly press release.

“The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy,” Dr. Drilon added.

About 1% to 2% of NSCLC tumors are thought to have a RET alteration.

The same trial also included patients with thyroid cancer.

Efficacy for MTC was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC who had previously been treated with cabozantinib, vandetanib, or both. The ORR in these patients was 69%.

In addition, selpercatinib was evaluated in 88 patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for these patients was 73%.

The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment. The ORR was 79%. Eight patients had received only RAI. The ORR for these patients was 100%.

In all the cases of thyroid cancer and lung cancer, among the patients who responded to treatment, the response lasted longer than 6 months.

“RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers,” Lori J. Wirth, MD, of Massachusetts General Hospital Cancer Center in Boston, noted in the company release.

A fact sheet from Eli Lilly notes that RET mutations are found in about 60% of sporadic MTC cases and in over 90% of familial MTC cases, and that RET fusions are found in approximately 10% to 20% of papillary thyroid cancers.

“For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET,” Dr. Wirth commented. “Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option.”

In the LIBRETTO-001 trial, the rate of discontinuations because of adverse reactions (ARs) was 5%, the company reported. The most common ARs, including laboratory abnormalities (≥25%), were increased aspartate aminotransferase level, increased alanine aminotransferase level, increased glucose level, decreased leukocyte count, decreased albumin level, decreased calcium level, dry mouth, diarrhea, increased creatinine level, increased alkaline phosphatase level, hypertension, fatigue, edema, decreased platelet count, increased total cholesterol level, rash, decreased sodium levels, and constipation. The most frequent serious AR (≥2%) was pneumonia.

The FDA warned that selpercatinib can cause hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions. It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women.

Selpercatinib is currently being assessed in two phase 3 confirmatory trials. LIBRETTO-431 will test the drug in previously untreated patients with RET-positive NSCLC. LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

The company that developed selpercaptinib, Loxo Oncology, was acquired by Eli Lilly last year in an $8 billion takeover. This drug was billed as the most promising asset in that deal, alongside oral BTK inhibitor LOXO-305, according to a report in Pharmaphorum.

Loxo developed Vitrakvi (larotrectinib), the first TRK inhibitor to reach the market, as well as the follow-up drug LOXO-195. Both were acquired by Bayer ahead of the Lilly takeover, that report notes.

This article first appeared on Medscape.com.