Clinical Edge Journal Scan

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: Tyrosine kinase inhibitor (TKI) therapy is associated with a higher burden of adverse events in patients with chronic myelogenous leukemia (CML). Later-generation TKIs may have greater toxicity than imatinib.

Major finding: The 5-year cumulative incidence of almost all major organ system outcomes was significantly higher for the CML + TKI vs. noncancer group (P less than .05). In the first year, later-generation TKIs vs. imatinib were associated with primary infections (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.02-2.00), circulatory events (HR, 1.15; 95% CI, 1.01-1.31), and skin issues (HR, 1.43; 95% CI, 1.13-1.80). Musculoskeletal and nervous system/sensory issues were less common with later-generation TKIs vs. imatinib (HR, 0.83-0.84; P less than .05).

Study details: This real-world analysis of health plan enrollees evaluated adverse events in CML patients treated with TKI (n = 1,200) compared with a noncancer cohort (n = 7,635; median follow-up, approximately 3 years).

Disclosures: The study was funded by Stand Up To Cancer, the American Association for Cancer Research, and the U.S. National Institutes of Health. The authors declared no conflicts of interest.

Source: Chow EJ et al. Leuk Lymphoma. 2020 Dec 7. doi: 10.1080/10428194.2020.1855340.

Key clinical point: Tyrosine kinase inhibitor (TKI) therapy is associated with a higher burden of adverse events in patients with chronic myelogenous leukemia (CML). Later-generation TKIs may have greater toxicity than imatinib.

Major finding: The 5-year cumulative incidence of almost all major organ system outcomes was significantly higher for the CML + TKI vs. noncancer group (P less than .05). In the first year, later-generation TKIs vs. imatinib were associated with primary infections (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.02-2.00), circulatory events (HR, 1.15; 95% CI, 1.01-1.31), and skin issues (HR, 1.43; 95% CI, 1.13-1.80). Musculoskeletal and nervous system/sensory issues were less common with later-generation TKIs vs. imatinib (HR, 0.83-0.84; P less than .05).

Study details: This real-world analysis of health plan enrollees evaluated adverse events in CML patients treated with TKI (n = 1,200) compared with a noncancer cohort (n = 7,635; median follow-up, approximately 3 years).

Disclosures: The study was funded by Stand Up To Cancer, the American Association for Cancer Research, and the U.S. National Institutes of Health. The authors declared no conflicts of interest.

Source: Chow EJ et al. Leuk Lymphoma. 2020 Dec 7. doi: 10.1080/10428194.2020.1855340.

Key clinical point: Tyrosine kinase inhibitor (TKI) therapy is associated with a higher burden of adverse events in patients with chronic myelogenous leukemia (CML). Later-generation TKIs may have greater toxicity than imatinib.

Major finding: The 5-year cumulative incidence of almost all major organ system outcomes was significantly higher for the CML + TKI vs. noncancer group (P less than .05). In the first year, later-generation TKIs vs. imatinib were associated with primary infections (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.02-2.00), circulatory events (HR, 1.15; 95% CI, 1.01-1.31), and skin issues (HR, 1.43; 95% CI, 1.13-1.80). Musculoskeletal and nervous system/sensory issues were less common with later-generation TKIs vs. imatinib (HR, 0.83-0.84; P less than .05).

Study details: This real-world analysis of health plan enrollees evaluated adverse events in CML patients treated with TKI (n = 1,200) compared with a noncancer cohort (n = 7,635; median follow-up, approximately 3 years).

Disclosures: The study was funded by Stand Up To Cancer, the American Association for Cancer Research, and the U.S. National Institutes of Health. The authors declared no conflicts of interest.

Source: Chow EJ et al. Leuk Lymphoma. 2020 Dec 7. doi: 10.1080/10428194.2020.1855340.

Key clinical point: Bosutinib is effective in patients with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) resistant/intolerant to prior therapy across age groups and the Charlson Comorbidity Index score without the age component (mCCI) scores.

Major finding: A substantial proportion of patients attained or maintained molecular response across age groups and mCCI scores molecular response. Older patients and those with mCCI ≥4 showed a trend towards higher rates of grade 3/4 treatment-related adverse events.

Study details: The data come from the ongoing, phase 4, single-arm, open-label BYOND study examining the safety and efficacy of bosutinib.

Disclosures: The study was sponsored by Pfizer. No data available regarding conflicts of interest.

Source: Gambacorti-Passerini C et al. Poster. Abstract 055. BSH 2020. 2020 Nov 9-14.

Key clinical point: Bosutinib is effective in patients with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) resistant/intolerant to prior therapy across age groups and the Charlson Comorbidity Index score without the age component (mCCI) scores.

Major finding: A substantial proportion of patients attained or maintained molecular response across age groups and mCCI scores molecular response. Older patients and those with mCCI ≥4 showed a trend towards higher rates of grade 3/4 treatment-related adverse events.

Study details: The data come from the ongoing, phase 4, single-arm, open-label BYOND study examining the safety and efficacy of bosutinib.

Disclosures: The study was sponsored by Pfizer. No data available regarding conflicts of interest.

Source: Gambacorti-Passerini C et al. Poster. Abstract 055. BSH 2020. 2020 Nov 9-14.

Key clinical point: Bosutinib is effective in patients with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) resistant/intolerant to prior therapy across age groups and the Charlson Comorbidity Index score without the age component (mCCI) scores.

Major finding: A substantial proportion of patients attained or maintained molecular response across age groups and mCCI scores molecular response. Older patients and those with mCCI ≥4 showed a trend towards higher rates of grade 3/4 treatment-related adverse events.

Study details: The data come from the ongoing, phase 4, single-arm, open-label BYOND study examining the safety and efficacy of bosutinib.

Disclosures: The study was sponsored by Pfizer. No data available regarding conflicts of interest.

Source: Gambacorti-Passerini C et al. Poster. Abstract 055. BSH 2020. 2020 Nov 9-14.

Key clinical point: Personalized treatment selection according to the LEukemia Artificial intelligence Program (LEAP) recommendations for patients with chronic myeloid leukemia in chronic phase (CML-CP) is associated with better likelihood of survival.

Major finding: The LEAP CML-CP recommendation was associated with an improved overall survival  (P less than 001).

Study details: A cohort of CML-CP patients was randomly assigned to training/validation (n = 504) and test cohorts (n = 126). The training/validation cohort was used to develop the LEAP CML-CP model using 101 variables at diagnosis. The test cohort was then applied to the LEAP CML-CP model and an optimum tyrosine kinase inhibitor therapy was selected for each patient.

Disclosures: The study was supported by the University of Texas MD Anderson Cancer Center Support Grant from the National Institutes of Health, the National Institutes of Health/National Cancer Institute under award, the University of Texas MD Anderson MDS/AML Moon Shot, and Leukemia Texas. K Sasaki, EJ Jabbour, F Ravandi, M Konopleva, G Garcia-Manero, JE Cortes,  C DiNardo reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Sasaki K et al. Am J Hematol. 2020 Nov 12.  doi: 10.1002/ajh.26047.

Key clinical point: Personalized treatment selection according to the LEukemia Artificial intelligence Program (LEAP) recommendations for patients with chronic myeloid leukemia in chronic phase (CML-CP) is associated with better likelihood of survival.

Major finding: The LEAP CML-CP recommendation was associated with an improved overall survival  (P less than 001).

Study details: A cohort of CML-CP patients was randomly assigned to training/validation (n = 504) and test cohorts (n = 126). The training/validation cohort was used to develop the LEAP CML-CP model using 101 variables at diagnosis. The test cohort was then applied to the LEAP CML-CP model and an optimum tyrosine kinase inhibitor therapy was selected for each patient.

Disclosures: The study was supported by the University of Texas MD Anderson Cancer Center Support Grant from the National Institutes of Health, the National Institutes of Health/National Cancer Institute under award, the University of Texas MD Anderson MDS/AML Moon Shot, and Leukemia Texas. K Sasaki, EJ Jabbour, F Ravandi, M Konopleva, G Garcia-Manero, JE Cortes,  C DiNardo reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Sasaki K et al. Am J Hematol. 2020 Nov 12.  doi: 10.1002/ajh.26047.

Key clinical point: Personalized treatment selection according to the LEukemia Artificial intelligence Program (LEAP) recommendations for patients with chronic myeloid leukemia in chronic phase (CML-CP) is associated with better likelihood of survival.

Major finding: The LEAP CML-CP recommendation was associated with an improved overall survival  (P less than 001).

Study details: A cohort of CML-CP patients was randomly assigned to training/validation (n = 504) and test cohorts (n = 126). The training/validation cohort was used to develop the LEAP CML-CP model using 101 variables at diagnosis. The test cohort was then applied to the LEAP CML-CP model and an optimum tyrosine kinase inhibitor therapy was selected for each patient.

Disclosures: The study was supported by the University of Texas MD Anderson Cancer Center Support Grant from the National Institutes of Health, the National Institutes of Health/National Cancer Institute under award, the University of Texas MD Anderson MDS/AML Moon Shot, and Leukemia Texas. K Sasaki, EJ Jabbour, F Ravandi, M Konopleva, G Garcia-Manero, JE Cortes,  C DiNardo reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Sasaki K et al. Am J Hematol. 2020 Nov 12.  doi: 10.1002/ajh.26047.

Key clinical point: There is a decline in renal function among patients with chronic myeloid leukaemia (CML) treated with tyrosine kinase inhibitors (TKIs).

Major finding: There was a significant reduction between the first and final recorded estimated glomerular filtration rate across all patients, declining by a mean of -12 mL/minute/1.73m² over the 10 years of measurement.

Study details: The data come from a retrospective analysis of 50 patients with CML treated with TKI therapy for at least 2 years.

Disclosures: No information on funding was available. The presenting author R Hinton declared no conflicts of interest. The second author S Arami reported relationships with various pharmaceutical companies.

Source: Hinton R et al. Poster. Abstract 053. BSH 2020. 2020 Nov 9-14.

Key clinical point: There is a decline in renal function among patients with chronic myeloid leukaemia (CML) treated with tyrosine kinase inhibitors (TKIs).

Major finding: There was a significant reduction between the first and final recorded estimated glomerular filtration rate across all patients, declining by a mean of -12 mL/minute/1.73m² over the 10 years of measurement.

Study details: The data come from a retrospective analysis of 50 patients with CML treated with TKI therapy for at least 2 years.

Disclosures: No information on funding was available. The presenting author R Hinton declared no conflicts of interest. The second author S Arami reported relationships with various pharmaceutical companies.

Source: Hinton R et al. Poster. Abstract 053. BSH 2020. 2020 Nov 9-14.

Key clinical point: There is a decline in renal function among patients with chronic myeloid leukaemia (CML) treated with tyrosine kinase inhibitors (TKIs).

Major finding: There was a significant reduction between the first and final recorded estimated glomerular filtration rate across all patients, declining by a mean of -12 mL/minute/1.73m² over the 10 years of measurement.

Study details: The data come from a retrospective analysis of 50 patients with CML treated with TKI therapy for at least 2 years.

Disclosures: No information on funding was available. The presenting author R Hinton declared no conflicts of interest. The second author S Arami reported relationships with various pharmaceutical companies.

Source: Hinton R et al. Poster. Abstract 053. BSH 2020. 2020 Nov 9-14.

Key clinical point: This analysis of more than 400 conceptions revealed that the rate of malformations was 2.5% in offsprings of fathers who did not discontinue tyrosine kinase inhibitors (TKIs) before conception, comparable to that measured in the general population.

Major finding: A total of 428 pregnancies from 374 fathers conceived without treatment discontinuation, 400 of which (93.5%) ended up in a live birth. Malformation was reported in 10 offsprings (2.5% of total live births): 6 with imatinib (1.9% of 313 live births), 2 with nilotinib (7.7% of 26 live births), 1 with dasatinib (2.3% of 43 live births), and none with bosutinib (0% of 12 live births).

Study details: A systematic review of 27 nonoverlapping cohorts of patients or case studies.

Disclosures: Study costs were covered by the Economic Development and Innovation Operative Programme Grant; Human Resources Development Operational Programme Grants; and the New National Excellence Programme, Ministry of Human Capacities. The authors declared no conflicts of interest.

Source: Szakács Z et al. PLoS One. 2020 Dec 3. doi: 10.1371/journal.pone.0243045.

Key clinical point: This analysis of more than 400 conceptions revealed that the rate of malformations was 2.5% in offsprings of fathers who did not discontinue tyrosine kinase inhibitors (TKIs) before conception, comparable to that measured in the general population.

Major finding: A total of 428 pregnancies from 374 fathers conceived without treatment discontinuation, 400 of which (93.5%) ended up in a live birth. Malformation was reported in 10 offsprings (2.5% of total live births): 6 with imatinib (1.9% of 313 live births), 2 with nilotinib (7.7% of 26 live births), 1 with dasatinib (2.3% of 43 live births), and none with bosutinib (0% of 12 live births).

Study details: A systematic review of 27 nonoverlapping cohorts of patients or case studies.

Disclosures: Study costs were covered by the Economic Development and Innovation Operative Programme Grant; Human Resources Development Operational Programme Grants; and the New National Excellence Programme, Ministry of Human Capacities. The authors declared no conflicts of interest.

Source: Szakács Z et al. PLoS One. 2020 Dec 3. doi: 10.1371/journal.pone.0243045.

Key clinical point: This analysis of more than 400 conceptions revealed that the rate of malformations was 2.5% in offsprings of fathers who did not discontinue tyrosine kinase inhibitors (TKIs) before conception, comparable to that measured in the general population.

Major finding: A total of 428 pregnancies from 374 fathers conceived without treatment discontinuation, 400 of which (93.5%) ended up in a live birth. Malformation was reported in 10 offsprings (2.5% of total live births): 6 with imatinib (1.9% of 313 live births), 2 with nilotinib (7.7% of 26 live births), 1 with dasatinib (2.3% of 43 live births), and none with bosutinib (0% of 12 live births).

Study details: A systematic review of 27 nonoverlapping cohorts of patients or case studies.

Disclosures: Study costs were covered by the Economic Development and Innovation Operative Programme Grant; Human Resources Development Operational Programme Grants; and the New National Excellence Programme, Ministry of Human Capacities. The authors declared no conflicts of interest.

Source: Szakács Z et al. PLoS One. 2020 Dec 3. doi: 10.1371/journal.pone.0243045.

Key clinical point: In patients with chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) discontinuation seems safe and feasible and is associated with improvements in patient-reported outcomes (PROs).

Major finding: Overall, 65.5% of patients stayed in major molecular response loss, 60.8% achieved treatment-free remission (TFR), and 34.5% had molecular recurrence (MRec). Detectable BCR-ABL1 by real-time quantitative polymerase chain reaction (PCR) or droplet digital PCR at the time of TKI discontinuation was associated with a greater risk of MRec. In patients who had reached TFR at 12 months, TKI discontinuation was associated with improvements in patient-reported fatigue, diarrhea, depression, and sleep disturbance.

Study details: In this prospective single-group nonrandomized LAST study, MRec and PROs after TKI discontinuation for 172 patients with CML in chronic phase (median age, 60 years) from 14 U.S. sites were evaluated. Included patients had well-controlled disease while treated with imatinib, dasatinib, nilotinib, or bosutinib.

Disclosures: This research was supported by a grant from the U.S. National Cancer Institute. The presenting author reported receiving personal fees from Novartis, Bristol Myers Squibb, and Takeda and research support from Novartis and Takeda.

Source: Atallah E et al. JAMA Oncol. 2020 Nov 12. doi: 10.1001/jamaoncol.2020.5774.

Key clinical point: In patients with chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) discontinuation seems safe and feasible and is associated with improvements in patient-reported outcomes (PROs).

Major finding: Overall, 65.5% of patients stayed in major molecular response loss, 60.8% achieved treatment-free remission (TFR), and 34.5% had molecular recurrence (MRec). Detectable BCR-ABL1 by real-time quantitative polymerase chain reaction (PCR) or droplet digital PCR at the time of TKI discontinuation was associated with a greater risk of MRec. In patients who had reached TFR at 12 months, TKI discontinuation was associated with improvements in patient-reported fatigue, diarrhea, depression, and sleep disturbance.

Study details: In this prospective single-group nonrandomized LAST study, MRec and PROs after TKI discontinuation for 172 patients with CML in chronic phase (median age, 60 years) from 14 U.S. sites were evaluated. Included patients had well-controlled disease while treated with imatinib, dasatinib, nilotinib, or bosutinib.

Disclosures: This research was supported by a grant from the U.S. National Cancer Institute. The presenting author reported receiving personal fees from Novartis, Bristol Myers Squibb, and Takeda and research support from Novartis and Takeda.

Source: Atallah E et al. JAMA Oncol. 2020 Nov 12. doi: 10.1001/jamaoncol.2020.5774.

Key clinical point: In patients with chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) discontinuation seems safe and feasible and is associated with improvements in patient-reported outcomes (PROs).

Major finding: Overall, 65.5% of patients stayed in major molecular response loss, 60.8% achieved treatment-free remission (TFR), and 34.5% had molecular recurrence (MRec). Detectable BCR-ABL1 by real-time quantitative polymerase chain reaction (PCR) or droplet digital PCR at the time of TKI discontinuation was associated with a greater risk of MRec. In patients who had reached TFR at 12 months, TKI discontinuation was associated with improvements in patient-reported fatigue, diarrhea, depression, and sleep disturbance.

Study details: In this prospective single-group nonrandomized LAST study, MRec and PROs after TKI discontinuation for 172 patients with CML in chronic phase (median age, 60 years) from 14 U.S. sites were evaluated. Included patients had well-controlled disease while treated with imatinib, dasatinib, nilotinib, or bosutinib.

Disclosures: This research was supported by a grant from the U.S. National Cancer Institute. The presenting author reported receiving personal fees from Novartis, Bristol Myers Squibb, and Takeda and research support from Novartis and Takeda.

Source: Atallah E et al. JAMA Oncol. 2020 Nov 12. doi: 10.1001/jamaoncol.2020.5774.

Key clinical point: Asciminib, a first-in-class STAMP inhibitor, may be a new treatment option for patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with 2 or more tyrosine kinase inhibitors.

Major finding: Major molecular response rate at 24 weeks was 25.5% with asciminib and 13.2% with bosutinib (BOS). The between-arm common treatment difference after adjustment for major cytogenetic response status at baseline was 12.2% (2-sided P = .029). Patients treated with asciminib were also twice as likely to achieve a deep molecular response. Grade 3 or greater adverse events were reported in 50.6% and 60.5% of patients receiving asciminib and BOS, respectively.

Study details: In this phase 3 ASCEMBL trial, 233 patients with CML-CP previously treated with 2 or more TKIs were randomly assigned (2:1) to receive asciminib 40 mg twice daily or BOS 500 mg once daily (median follow-up duration, 14.9 months).

Disclosures: The study is sponsored by Novartis. Some of the investigators reported ties with pharmaceutical companies, including Novartis.

Source: Hochhaus A et al. ASH Annual Meeting and Exposition 2020. Abstract LBA-4.

Key clinical point: Asciminib, a first-in-class STAMP inhibitor, may be a new treatment option for patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with 2 or more tyrosine kinase inhibitors.

Major finding: Major molecular response rate at 24 weeks was 25.5% with asciminib and 13.2% with bosutinib (BOS). The between-arm common treatment difference after adjustment for major cytogenetic response status at baseline was 12.2% (2-sided P = .029). Patients treated with asciminib were also twice as likely to achieve a deep molecular response. Grade 3 or greater adverse events were reported in 50.6% and 60.5% of patients receiving asciminib and BOS, respectively.

Study details: In this phase 3 ASCEMBL trial, 233 patients with CML-CP previously treated with 2 or more TKIs were randomly assigned (2:1) to receive asciminib 40 mg twice daily or BOS 500 mg once daily (median follow-up duration, 14.9 months).

Disclosures: The study is sponsored by Novartis. Some of the investigators reported ties with pharmaceutical companies, including Novartis.

Source: Hochhaus A et al. ASH Annual Meeting and Exposition 2020. Abstract LBA-4.

Key clinical point: Asciminib, a first-in-class STAMP inhibitor, may be a new treatment option for patients with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with 2 or more tyrosine kinase inhibitors.

Major finding: Major molecular response rate at 24 weeks was 25.5% with asciminib and 13.2% with bosutinib (BOS). The between-arm common treatment difference after adjustment for major cytogenetic response status at baseline was 12.2% (2-sided P = .029). Patients treated with asciminib were also twice as likely to achieve a deep molecular response. Grade 3 or greater adverse events were reported in 50.6% and 60.5% of patients receiving asciminib and BOS, respectively.

Study details: In this phase 3 ASCEMBL trial, 233 patients with CML-CP previously treated with 2 or more TKIs were randomly assigned (2:1) to receive asciminib 40 mg twice daily or BOS 500 mg once daily (median follow-up duration, 14.9 months).

Disclosures: The study is sponsored by Novartis. Some of the investigators reported ties with pharmaceutical companies, including Novartis.

Source: Hochhaus A et al. ASH Annual Meeting and Exposition 2020. Abstract LBA-4.

Breast cancer patients treated with curative intent do not often experience symptoms related to the cancer itself, and treatment toxicities may impact adherence and subsequently prognosis. Mittendorf et al reported on patient reported outcomes (PROs) from the phase 3 IMpassion031 trial which showed pCR improvement with atezolizumab/chemotherapy compared to placebo/chemotherapy for neoadjuvant early-stage TNBC. Health-related quality of life items and treatment-related symptoms worsened similarly in both arms during neoadjuvant therapy, and recovered/stabilized in the adjuvant setting. Further exploration of immunotherapy PROs is warranted, as clinical benefit is seen with these agents and they do not appear to negatively impact functioning and patient experience with treatment long-term. Side effect profiles of immunotherapy and standard chemotherapy are different, and design of immunotherapy-specific PROs are desired.

The PRIME 2 10 year results evaluating the role of whole breast irradiation in women ≥65 years with early-stage HR-positive breast cancer receiving hormonal therapy showed RT reduced risk of local recurrence from 9.8% to 0.9% at 10 years (p=0.0008). Patients with low ER tumors had higher 10 year local recurrence rate compared to high ER tumors (18.8% versus 9.2% (p0.007)). Rates of overall survival (80.4% in no RT group vs 81.0% in RT group) and metastasis free survival were similar. A shared decision making approach is key, carefully weighing benefits and risks, considering pathologic features, patient preferences and co-morbidities that may influence endocrine therapy adherence. The impact of molecular subtypes and genomic assays is also being explored to help assess radiation benefit and guide treatment recommendations.

Breast cancer in young women presents unique challenges considering the lifetime period during which diagnosis occurs. Previous studies have supported the safety of pregnancy after breast cancer and guidelines recommend oncofertility counseling in young patients. Blondeaux et al found that breast cancer patients had a 60% lower chance of pregnancy after treatment and were more likely to have complications including low birth weight, small for gestational age, preterm delivery and cesarean section. Although increased risk of congenital abnormalities did not appear to be statistically significant, the HR was 1.63. Importantly, pregnancy after breast cancer did not negatively impact maternal outcomes. This study further supports the safety of pregnancy after breast cancer, highlights the need for close monitoring of pregnancies in these women, and emphasizes the importance of fertility and family planning discussion, which is most optimally provided in a multidisciplinary fashion.

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Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2020;55:45-54.

Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47:74-83.

Breast cancer patients treated with curative intent do not often experience symptoms related to the cancer itself, and treatment toxicities may impact adherence and subsequently prognosis. Mittendorf et al reported on patient reported outcomes (PROs) from the phase 3 IMpassion031 trial which showed pCR improvement with atezolizumab/chemotherapy compared to placebo/chemotherapy for neoadjuvant early-stage TNBC. Health-related quality of life items and treatment-related symptoms worsened similarly in both arms during neoadjuvant therapy, and recovered/stabilized in the adjuvant setting. Further exploration of immunotherapy PROs is warranted, as clinical benefit is seen with these agents and they do not appear to negatively impact functioning and patient experience with treatment long-term. Side effect profiles of immunotherapy and standard chemotherapy are different, and design of immunotherapy-specific PROs are desired.

The PRIME 2 10 year results evaluating the role of whole breast irradiation in women ≥65 years with early-stage HR-positive breast cancer receiving hormonal therapy showed RT reduced risk of local recurrence from 9.8% to 0.9% at 10 years (p=0.0008). Patients with low ER tumors had higher 10 year local recurrence rate compared to high ER tumors (18.8% versus 9.2% (p0.007)). Rates of overall survival (80.4% in no RT group vs 81.0% in RT group) and metastasis free survival were similar. A shared decision making approach is key, carefully weighing benefits and risks, considering pathologic features, patient preferences and co-morbidities that may influence endocrine therapy adherence. The impact of molecular subtypes and genomic assays is also being explored to help assess radiation benefit and guide treatment recommendations.

Breast cancer in young women presents unique challenges considering the lifetime period during which diagnosis occurs. Previous studies have supported the safety of pregnancy after breast cancer and guidelines recommend oncofertility counseling in young patients. Blondeaux et al found that breast cancer patients had a 60% lower chance of pregnancy after treatment and were more likely to have complications including low birth weight, small for gestational age, preterm delivery and cesarean section. Although increased risk of congenital abnormalities did not appear to be statistically significant, the HR was 1.63. Importantly, pregnancy after breast cancer did not negatively impact maternal outcomes. This study further supports the safety of pregnancy after breast cancer, highlights the need for close monitoring of pregnancies in these women, and emphasizes the importance of fertility and family planning discussion, which is most optimally provided in a multidisciplinary fashion.

References:

Dent R, Oliveira AM, Isakoff SJ, Im SA, Espié M, Blau S, Saura C, Wongchenko MJ, Xu N, Bradley D, Reilly SJ, Mani A, Kim SB. Final results of the double-blind placebo (PBO)-controlled randomised phase II LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for inoperable locally advanced/metastatic triple-negative breast cancer (mTNBC). Presented during 2020 ESMO breast cancer virtual meeting; May 23-24, 2020. Abstract 139O.

Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423-433.

Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396:1090-1100.

King-Kallimanis BL, Howie LJ, Roydhouse JK, Singh H, Theoret MR, Blumenthal GM, Kluetz PG. Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions. Clin Trials. 2019;16:322-326.

Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2020;55:45-54.

Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47:74-83.

Breast cancer patients treated with curative intent do not often experience symptoms related to the cancer itself, and treatment toxicities may impact adherence and subsequently prognosis. Mittendorf et al reported on patient reported outcomes (PROs) from the phase 3 IMpassion031 trial which showed pCR improvement with atezolizumab/chemotherapy compared to placebo/chemotherapy for neoadjuvant early-stage TNBC. Health-related quality of life items and treatment-related symptoms worsened similarly in both arms during neoadjuvant therapy, and recovered/stabilized in the adjuvant setting. Further exploration of immunotherapy PROs is warranted, as clinical benefit is seen with these agents and they do not appear to negatively impact functioning and patient experience with treatment long-term. Side effect profiles of immunotherapy and standard chemotherapy are different, and design of immunotherapy-specific PROs are desired.

The PRIME 2 10 year results evaluating the role of whole breast irradiation in women ≥65 years with early-stage HR-positive breast cancer receiving hormonal therapy showed RT reduced risk of local recurrence from 9.8% to 0.9% at 10 years (p=0.0008). Patients with low ER tumors had higher 10 year local recurrence rate compared to high ER tumors (18.8% versus 9.2% (p0.007)). Rates of overall survival (80.4% in no RT group vs 81.0% in RT group) and metastasis free survival were similar. A shared decision making approach is key, carefully weighing benefits and risks, considering pathologic features, patient preferences and co-morbidities that may influence endocrine therapy adherence. The impact of molecular subtypes and genomic assays is also being explored to help assess radiation benefit and guide treatment recommendations.

Breast cancer in young women presents unique challenges considering the lifetime period during which diagnosis occurs. Previous studies have supported the safety of pregnancy after breast cancer and guidelines recommend oncofertility counseling in young patients. Blondeaux et al found that breast cancer patients had a 60% lower chance of pregnancy after treatment and were more likely to have complications including low birth weight, small for gestational age, preterm delivery and cesarean section. Although increased risk of congenital abnormalities did not appear to be statistically significant, the HR was 1.63. Importantly, pregnancy after breast cancer did not negatively impact maternal outcomes. This study further supports the safety of pregnancy after breast cancer, highlights the need for close monitoring of pregnancies in these women, and emphasizes the importance of fertility and family planning discussion, which is most optimally provided in a multidisciplinary fashion.

References:

Dent R, Oliveira AM, Isakoff SJ, Im SA, Espié M, Blau S, Saura C, Wongchenko MJ, Xu N, Bradley D, Reilly SJ, Mani A, Kim SB. Final results of the double-blind placebo (PBO)-controlled randomised phase II LOTUS trial of first-line ipatasertib (IPAT) + paclitaxel (PAC) for inoperable locally advanced/metastatic triple-negative breast cancer (mTNBC). Presented during 2020 ESMO breast cancer virtual meeting; May 23-24, 2020. Abstract 139O.

Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero JM, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker SJ, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423-433.

Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396:1090-1100.

King-Kallimanis BL, Howie LJ, Roydhouse JK, Singh H, Theoret MR, Blumenthal GM, Kluetz PG. Patient reported outcomes in anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data submitted and future directions. Clin Trials. 2019;16:322-326.

Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2020;55:45-54.

Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47:74-83.

Key clinical point: Omitting adjuvant radiotherapy may be an option for some older women with low-risk, hormone receptor-positive breast cancer who are receiving appropriate endocrine treatment.

Major finding: The 10-year rate of ipsilateral recurrence was lower with radiotherapy than without (0.9% vs. 9.8%, P = .00008), but there was no significant between-arm difference in 10-year overall survival (81.0% and 80.4%, respectively; P = .68).

Study details: A phase 3, randomized trial of 1,326 women age 65 and older with hormone receptor–positive, low-risk early breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine therapy with or without whole breast irradiation (40-50 Gy in 15-25 fractions).

Disclosures: The study was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Dr. Kunkler did not have any disclosures.

Source: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.

Key clinical point: Omitting adjuvant radiotherapy may be an option for some older women with low-risk, hormone receptor-positive breast cancer who are receiving appropriate endocrine treatment.

Major finding: The 10-year rate of ipsilateral recurrence was lower with radiotherapy than without (0.9% vs. 9.8%, P = .00008), but there was no significant between-arm difference in 10-year overall survival (81.0% and 80.4%, respectively; P = .68).

Study details: A phase 3, randomized trial of 1,326 women age 65 and older with hormone receptor–positive, low-risk early breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine therapy with or without whole breast irradiation (40-50 Gy in 15-25 fractions).

Disclosures: The study was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Dr. Kunkler did not have any disclosures.

Source: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.

Key clinical point: Omitting adjuvant radiotherapy may be an option for some older women with low-risk, hormone receptor-positive breast cancer who are receiving appropriate endocrine treatment.

Major finding: The 10-year rate of ipsilateral recurrence was lower with radiotherapy than without (0.9% vs. 9.8%, P = .00008), but there was no significant between-arm difference in 10-year overall survival (81.0% and 80.4%, respectively; P = .68).

Study details: A phase 3, randomized trial of 1,326 women age 65 and older with hormone receptor–positive, low-risk early breast cancer undergoing breast-conserving surgery and receiving adjuvant endocrine therapy with or without whole breast irradiation (40-50 Gy in 15-25 fractions).

Disclosures: The study was funded by the Chief Scientist Office (Scottish Government) and the Breast Cancer Institute at the Western General Hospital in Edinburgh, Scotland. Dr. Kunkler did not have any disclosures.

Source: Kunkler IH J et al. SABCS 2020, Abstract GS2-03.