Clinical Edge Journal Scan

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: De-escalation of tyrosine kinase inhibitor (TKI) therapy from continuous to intermittent (1 month ON/OFF) schedule effectively maintained molecular response 3/4 (MR3/4) during the first year in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The 1-year probability of maintaining MR3 with intermittent TKI therapy was 81% (95% confidence interval, 75%-87%). Of the 39 patients who lost MR, 95% regained at least MR3 within 6 months of resuming continuous TKI. No treatment-related adverse events were reported.

Study details: Findings are from the first interim analysis of the phase 3 OPTkIMA trial including 185 patients with CML-CP (age, 60 years or more) who were in stable MR3/4 after 2 or more years of daily treatment with TKI.

Disclosures: The authors did not report any source of funding. The lead author had no disclosures. Some other coinvestigators reported ties with various pharmaceutical companies.

Source: Malagola M et al. Cancer Med. 2021 Feb 16. doi: 10.1002/cam4.3778.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: BCR/ABL transcript type B3a2_e14a2 is more common than B2a2_e13a2 in patients with chronic myeloid leukemia (CML) with B3a2_e14a2 being more common in women than men.

Major finding: The overall estimated prevalence was highest for B3a2_e14a2 transcript (54%), followed by B2a2_e13a2 (39%) and dual B2a2_e13a2/B3a2_e14a2 (1.11%) transcripts (all P less than .0001), with B3a2_e14a2 being more prevalent in women vs. men (60.6% vs. 51.1%; P less than .0001).

Study details: Findings are from a meta-analysis of 34 studies that evaluated the prevalence of main BCR/ABL transcript types in patients with CML.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Ghalesardi OK et al. Leuk Res. 2021 Jan 19. doi: 10.1016/j.leukres.2021.106512.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Right ventricular systolic pressure (RVSP) increased significantly following dasatinib therapy in some patients with chronic-phase chronic myeloid leukemia (CML-CP), leading to dasatinib-induced pulmonary arterial hypertension (D-PAH) and consequent therapy discontinuation.

Major finding: During a median of 36.2 months of dasatinib therapy, mean RSVP increased significantly and gradually (P less than .001). Overall, 56 patients had RVSP over 40 mmHg, of which 51.8% of patients were diagnosed with D-PAH with clinical symptoms, all ultimately switching to other tyrosine kinase inhibitors.

Study details: Findings are from an analysis of a cohort of 451 patients with CML-CP who underwent 2D-echocardiography at least once at baseline and/or during dasatinib therapy (mean dose, 85 mg/day) as frontline (n=196) and subsequent line (n=255).

Disclosures: This study was funded by Korea Leukemia Bank. The authors declared no conflicts of interest.

Source: Lee SE et al. Cancer Med. 2021 Feb 15. doi: 10.1002/cam4.3588.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: Asciminib is a safe and effective drug in patients with chronic myeloid leukemia (CML) without treatment alternatives in common clinical practice.

Major finding: After a median of 8.8 months on asciminib, the cumulative response rates of complete hematologic response, complete cytogenetic response, and major molecular response were 100%, 66%, and 41%, respectively. Improvement in baseline response and maintenance of baseline response were observed in 55% and 90% of patients, respectively. At last evaluation, 87% of patients remained on asciminib treatment with none discontinuing because of treatment-emergent adverse events.

Study details: Findings are from a retrospective analysis of 31 BCR-ABL1-positive patients with CML treated with asciminib. Patients were heavily treated and switched to asciminib because of intolerance (n=22) or resistance (n=9) to prior tyrosine kinase inhibitors. All patients were treated under the managed-access program by Novartis.

Disclosures: No information on funding was available. Four of the authors including the lead author reported being on advisory committees, receiving funds, and/or speaker honoraria from various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Garcia-Gutiérrez V et al. Blood Cancer J. 2021 Feb 9. doi: 10.1038/s41408-021-00420-8.

Key clinical point: At 2 years, molecular recurrence-free survival (MRFS) after imatinib discontinuation was observed in over half of the patients with chronic phase-chronic myeloid leukemia (CML-CP) with sustained molecular response of 4log (MR4). MR of 4.5log (MR4.5) was associated with a lower risk of relapse.

Major finding: At 24 months, MRFS was 54% (95% CI, 39%-75%). Molecular relapse was observed in 42% of patients. All patients reachieved major molecular response after resuming imatinib. MR4.5 at discontinuation was associated with a lower risk of molecular relapse (odds ratio, 0.32; P = .03).

Study details: Findings are from a prospective study that evaluated treatment-free survival after imatinib discontinuation in 31 patients with CML-CP with sustained MR4 for at least 12 months and treated with first-line imatinib for at least 36 months.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

Source: Seguro FS et al. Leuk Res. 2021 Jan 21. doi: 10.1016/j.leukres.2021.106516.

Key clinical point: At 2 years, molecular recurrence-free survival (MRFS) after imatinib discontinuation was observed in over half of the patients with chronic phase-chronic myeloid leukemia (CML-CP) with sustained molecular response of 4log (MR4). MR of 4.5log (MR4.5) was associated with a lower risk of relapse.

Major finding: At 24 months, MRFS was 54% (95% CI, 39%-75%). Molecular relapse was observed in 42% of patients. All patients reachieved major molecular response after resuming imatinib. MR4.5 at discontinuation was associated with a lower risk of molecular relapse (odds ratio, 0.32; P = .03).

Study details: Findings are from a prospective study that evaluated treatment-free survival after imatinib discontinuation in 31 patients with CML-CP with sustained MR4 for at least 12 months and treated with first-line imatinib for at least 36 months.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

Source: Seguro FS et al. Leuk Res. 2021 Jan 21. doi: 10.1016/j.leukres.2021.106516.

Key clinical point: At 2 years, molecular recurrence-free survival (MRFS) after imatinib discontinuation was observed in over half of the patients with chronic phase-chronic myeloid leukemia (CML-CP) with sustained molecular response of 4log (MR4). MR of 4.5log (MR4.5) was associated with a lower risk of relapse.

Major finding: At 24 months, MRFS was 54% (95% CI, 39%-75%). Molecular relapse was observed in 42% of patients. All patients reachieved major molecular response after resuming imatinib. MR4.5 at discontinuation was associated with a lower risk of molecular relapse (odds ratio, 0.32; P = .03).

Study details: Findings are from a prospective study that evaluated treatment-free survival after imatinib discontinuation in 31 patients with CML-CP with sustained MR4 for at least 12 months and treated with first-line imatinib for at least 36 months.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

Source: Seguro FS et al. Leuk Res. 2021 Jan 21. doi: 10.1016/j.leukres.2021.106516.

Key clinical point: Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) with a higher dasatinib dose adjusted for body weight (dose/BW) experienced a higher risk of dose-limiting toxicities (DLTs). The fixed starting dose of dasatinib 100 mg may not be optimal in Asian patients.

Major finding: By 36 months after initiation of dasatinib 100 mg once daily (OD) as frontline therapy, 55.9% of patients experienced at least 1 DLT. Higher dasatinib dose/BW was associated with a higher risk of DLT occurrence (odds ratio, 4.84; P = .03).

Study details: This study assessed the effect of a fixed starting dose of dasatinib (100 mg OD) in 102 Asian patients with newly diagnosed CML-CP.

Disclosures: This study was funded by the National Research Foundation of Korea, the Foundation of Pharmacy Education and Research, and the Research Institutes of Pharmaceutical Sciences (Seoul National University). The lead author had no disclosures. DW Kim reported the use of clinical data collected from a separate research study (funded by Bristol-Myers Squibb) for this study.

Source: Shin H et al. Clin Lymphoma Myeloma Leuk. 2021 Feb 1 doi: 10.1016/j.clml.2021.01.020.

Key clinical point: Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) with a higher dasatinib dose adjusted for body weight (dose/BW) experienced a higher risk of dose-limiting toxicities (DLTs). The fixed starting dose of dasatinib 100 mg may not be optimal in Asian patients.

Major finding: By 36 months after initiation of dasatinib 100 mg once daily (OD) as frontline therapy, 55.9% of patients experienced at least 1 DLT. Higher dasatinib dose/BW was associated with a higher risk of DLT occurrence (odds ratio, 4.84; P = .03).

Study details: This study assessed the effect of a fixed starting dose of dasatinib (100 mg OD) in 102 Asian patients with newly diagnosed CML-CP.

Disclosures: This study was funded by the National Research Foundation of Korea, the Foundation of Pharmacy Education and Research, and the Research Institutes of Pharmaceutical Sciences (Seoul National University). The lead author had no disclosures. DW Kim reported the use of clinical data collected from a separate research study (funded by Bristol-Myers Squibb) for this study.

Source: Shin H et al. Clin Lymphoma Myeloma Leuk. 2021 Feb 1 doi: 10.1016/j.clml.2021.01.020.

Key clinical point: Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) with a higher dasatinib dose adjusted for body weight (dose/BW) experienced a higher risk of dose-limiting toxicities (DLTs). The fixed starting dose of dasatinib 100 mg may not be optimal in Asian patients.

Major finding: By 36 months after initiation of dasatinib 100 mg once daily (OD) as frontline therapy, 55.9% of patients experienced at least 1 DLT. Higher dasatinib dose/BW was associated with a higher risk of DLT occurrence (odds ratio, 4.84; P = .03).

Study details: This study assessed the effect of a fixed starting dose of dasatinib (100 mg OD) in 102 Asian patients with newly diagnosed CML-CP.

Disclosures: This study was funded by the National Research Foundation of Korea, the Foundation of Pharmacy Education and Research, and the Research Institutes of Pharmaceutical Sciences (Seoul National University). The lead author had no disclosures. DW Kim reported the use of clinical data collected from a separate research study (funded by Bristol-Myers Squibb) for this study.

Source: Shin H et al. Clin Lymphoma Myeloma Leuk. 2021 Feb 1 doi: 10.1016/j.clml.2021.01.020.

Key clinical point: Late relapses do occur after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) at 36 months, with molecular response (MR) status at 36 months being highly predictive of subsequent molecular relapse.

Major finding: During a follow-up of 72 months, 10.8% of patients in TFR at 36 months lost major MR. Not being in MR4 at 36 months of TKI discontinuation was associated with an 85% higher risk of molecular relapse during the subsequent 3 years.

Study details: Findings are from the 6-year follow-up (AFTER-SKI) of 111 patients with CML-CP who were in TFR at 36 months after TKI discontinuation from the EURO-SKI trial.

Disclosures: This study was funded by Lund University and Skane University Hospital. U Olsson-Strömberg, P Koskenvesa, and D Žáčková reported consulting for, being on speaker’s and advisory boards, or receiving honoraria from various pharmaceutical companies. The remaining authors had no disclosures.

Source: Richter J et al. Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01173-w.

Key clinical point: Late relapses do occur after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) at 36 months, with molecular response (MR) status at 36 months being highly predictive of subsequent molecular relapse.

Major finding: During a follow-up of 72 months, 10.8% of patients in TFR at 36 months lost major MR. Not being in MR4 at 36 months of TKI discontinuation was associated with an 85% higher risk of molecular relapse during the subsequent 3 years.

Study details: Findings are from the 6-year follow-up (AFTER-SKI) of 111 patients with CML-CP who were in TFR at 36 months after TKI discontinuation from the EURO-SKI trial.

Disclosures: This study was funded by Lund University and Skane University Hospital. U Olsson-Strömberg, P Koskenvesa, and D Žáčková reported consulting for, being on speaker’s and advisory boards, or receiving honoraria from various pharmaceutical companies. The remaining authors had no disclosures.

Source: Richter J et al. Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01173-w.

Key clinical point: Late relapses do occur after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic-phase chronic myeloid leukemia (CML-CP) in treatment-free remission (TFR) at 36 months, with molecular response (MR) status at 36 months being highly predictive of subsequent molecular relapse.

Major finding: During a follow-up of 72 months, 10.8% of patients in TFR at 36 months lost major MR. Not being in MR4 at 36 months of TKI discontinuation was associated with an 85% higher risk of molecular relapse during the subsequent 3 years.

Study details: Findings are from the 6-year follow-up (AFTER-SKI) of 111 patients with CML-CP who were in TFR at 36 months after TKI discontinuation from the EURO-SKI trial.

Disclosures: This study was funded by Lund University and Skane University Hospital. U Olsson-Strömberg, P Koskenvesa, and D Žáčková reported consulting for, being on speaker’s and advisory boards, or receiving honoraria from various pharmaceutical companies. The remaining authors had no disclosures.

Source: Richter J et al. Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01173-w.

Key clinical point: Combination of imatinib (IM) with cytarabine (AraC) or pegylated interferon alpha2a (PegIFN-α2a) or a higher IM dose (600 mg; IM-600) did not improve long-term survival vs. IM 400 mg (IM-400) in patients with chronic myeloid leukemia in the chronic phase (CML-CP).

Major finding: At 15 years, overall survival was similar across IM-400 (85%; 95% confidence interval [CI], 78%-90%), IM-600 (83%; 95% CI, 75%-88%), IM-400+AraC (80%; 95% CI, 73%-85%), and IM-400+PegIFN-α2a (82%; 95% CI, 75%-87%) arms. Progression-free survival was also similar between arms.

Study details: Findings are from French SPIRIT phase 3 trial including 787 patients with CML-CP randomly allocated to frontline treatment with IM-400 (n=223), IM-600 (n=171), IM-400+AraC (n=172), and IM-400+PegIFN-α2a (n=221).

Disclosures: The trial was supported by grants from the French Minister of Health, Novartis, and Roche Pharma. The lead author reported ties with Novartis, Roche, BMS, and Celgene. Some of the other authors also declared receiving honoraria and/or research support from various pharmaceutical companies.

Source: Guilhot F et al. Leukemia. 2021 Jan 22. doi: 10.1038/s41375-020-01117-w.

Key clinical point: Combination of imatinib (IM) with cytarabine (AraC) or pegylated interferon alpha2a (PegIFN-α2a) or a higher IM dose (600 mg; IM-600) did not improve long-term survival vs. IM 400 mg (IM-400) in patients with chronic myeloid leukemia in the chronic phase (CML-CP).

Major finding: At 15 years, overall survival was similar across IM-400 (85%; 95% confidence interval [CI], 78%-90%), IM-600 (83%; 95% CI, 75%-88%), IM-400+AraC (80%; 95% CI, 73%-85%), and IM-400+PegIFN-α2a (82%; 95% CI, 75%-87%) arms. Progression-free survival was also similar between arms.

Study details: Findings are from French SPIRIT phase 3 trial including 787 patients with CML-CP randomly allocated to frontline treatment with IM-400 (n=223), IM-600 (n=171), IM-400+AraC (n=172), and IM-400+PegIFN-α2a (n=221).

Disclosures: The trial was supported by grants from the French Minister of Health, Novartis, and Roche Pharma. The lead author reported ties with Novartis, Roche, BMS, and Celgene. Some of the other authors also declared receiving honoraria and/or research support from various pharmaceutical companies.

Source: Guilhot F et al. Leukemia. 2021 Jan 22. doi: 10.1038/s41375-020-01117-w.

Key clinical point: Combination of imatinib (IM) with cytarabine (AraC) or pegylated interferon alpha2a (PegIFN-α2a) or a higher IM dose (600 mg; IM-600) did not improve long-term survival vs. IM 400 mg (IM-400) in patients with chronic myeloid leukemia in the chronic phase (CML-CP).

Major finding: At 15 years, overall survival was similar across IM-400 (85%; 95% confidence interval [CI], 78%-90%), IM-600 (83%; 95% CI, 75%-88%), IM-400+AraC (80%; 95% CI, 73%-85%), and IM-400+PegIFN-α2a (82%; 95% CI, 75%-87%) arms. Progression-free survival was also similar between arms.

Study details: Findings are from French SPIRIT phase 3 trial including 787 patients with CML-CP randomly allocated to frontline treatment with IM-400 (n=223), IM-600 (n=171), IM-400+AraC (n=172), and IM-400+PegIFN-α2a (n=221).

Disclosures: The trial was supported by grants from the French Minister of Health, Novartis, and Roche Pharma. The lead author reported ties with Novartis, Roche, BMS, and Celgene. Some of the other authors also declared receiving honoraria and/or research support from various pharmaceutical companies.

Source: Guilhot F et al. Leukemia. 2021 Jan 22. doi: 10.1038/s41375-020-01117-w.

Peripheral neuropathy is a well-recognized complication of taxane therapy that can impact functioning and quality of life. Dose-reductions are applied in an effort to continue treatment and minimize risk of worsening neuropathy. In a prospective analysis of breast cancer patients receiving weekly paclitaxel, Timmins et al showed neuropathy symptoms affected 85% with severe symptoms in 38%, and about half of the cohort had persistent symptoms up to 12 months post-chemotherapy. Patients who received dose reductions reported worse neuropathy and symptom burden compared to those who received full dose paclitaxel chemotherapy. It is challenging to predict with certainty which patients may experience significant neuropathy, and important to acknowledge individual patients factors such as age and other medical co-morbidities. Additional research is warranted to refine individual risk assessment as well as prevention and management strategies.

The treatment landscape for metastatic HER2-positive breast cancer is evolving at a rapid pace. Margetuximab is a chimeric antibody with similar epitope specificity to trastuzumab, but with an engineered Fc region that enhances immune activation. The phase 3 SOPHIA trial included 536 patients with pretreated HER2-positive advanced breast cancer and demonstrated modest improvement in progression free-survival with margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy (median PFS 5.8 versus 4.9 months; HR 0.76, p=0.03). The introduction of other therapies in this space (tucatinib, trastuzumab deruxtecan, neratinib) provides patients with many options, but simultaneously creates a complex treatment algorithm when it comes to therapy selection. Toxicity profiles and sites of metastases should be taken into consideration when deciding on best therapy for an individual patient.

Given the impressive outcomes seen with endocrine therapy plus CDK 4/6 inhibitors in the advanced HR+/HER2- population, these combinations are being studied in the curative setting. The phase 3 PALLAS study randomized 5,760 patients with stage I-III HR+/HER2- breast cancer to ongoing endocrine therapy with or without palbociclib for 2 years. Data from the second interim analysis of this trial showed similar invasive disease-free survival rates for the two arms (3 years iDFS 88.2% for palbociclib plus endocrine therapy versus 88.5% for endocrine therapy alone; HR 0.93, p=0.51). In contrast, the phase 3 monarchE trial showed improvement in iDFS with abemaciclib for 2 years with ongoing endocrine therapy compared to endocrine therapy alone (2 year iDFS rate of 92.3% versus 89.3%; HR 0.713, p=0.0009). Differences in study populations, mechanism of action of various CDK 4/6 inhibitors, dosing and drug exposure, may possibly impact results. Long-term follow-up and biomarker studies are desired to further delineate the role of CDK 4/6 inhibitors in this setting.

References:

Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, Cannady RS, Pratt-Chapman ML, Edge SB, Jacobs LA, Hurria A, Marks LB, LaMonte SJ, Warner E, Lyman GH, Ganz PA. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. 2016;34:611-35.

Ghoreishi Z, Keshavarz S, Asghari Jafarabadi M, Fathifar Z, Goodman KA, Esfahani A. Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer. BMC Cancer. 2018;18:958.

O'Shaughnessy JA, Johnston S, Harbeck N, Toi M, Im Y-H, Reinisch M, Shao Z, Kellokumpu Lehtinen PL, Huang C-S, Tryakin A, Goetz M, Rugo HS, Senkus E, Testa L, Andersson M, Tamura K, Steger GG, Del Mastro L, Cox J, Forrester T, Sherwood S, Li X, Wei R, Martin M, Rastogi P. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high risk early breast cancer. Presented at: 2020 Virtual San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract GS1-01.

Peripheral neuropathy is a well-recognized complication of taxane therapy that can impact functioning and quality of life. Dose-reductions are applied in an effort to continue treatment and minimize risk of worsening neuropathy. In a prospective analysis of breast cancer patients receiving weekly paclitaxel, Timmins et al showed neuropathy symptoms affected 85% with severe symptoms in 38%, and about half of the cohort had persistent symptoms up to 12 months post-chemotherapy. Patients who received dose reductions reported worse neuropathy and symptom burden compared to those who received full dose paclitaxel chemotherapy. It is challenging to predict with certainty which patients may experience significant neuropathy, and important to acknowledge individual patients factors such as age and other medical co-morbidities. Additional research is warranted to refine individual risk assessment as well as prevention and management strategies.

The treatment landscape for metastatic HER2-positive breast cancer is evolving at a rapid pace. Margetuximab is a chimeric antibody with similar epitope specificity to trastuzumab, but with an engineered Fc region that enhances immune activation. The phase 3 SOPHIA trial included 536 patients with pretreated HER2-positive advanced breast cancer and demonstrated modest improvement in progression free-survival with margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy (median PFS 5.8 versus 4.9 months; HR 0.76, p=0.03). The introduction of other therapies in this space (tucatinib, trastuzumab deruxtecan, neratinib) provides patients with many options, but simultaneously creates a complex treatment algorithm when it comes to therapy selection. Toxicity profiles and sites of metastases should be taken into consideration when deciding on best therapy for an individual patient.

Given the impressive outcomes seen with endocrine therapy plus CDK 4/6 inhibitors in the advanced HR+/HER2- population, these combinations are being studied in the curative setting. The phase 3 PALLAS study randomized 5,760 patients with stage I-III HR+/HER2- breast cancer to ongoing endocrine therapy with or without palbociclib for 2 years. Data from the second interim analysis of this trial showed similar invasive disease-free survival rates for the two arms (3 years iDFS 88.2% for palbociclib plus endocrine therapy versus 88.5% for endocrine therapy alone; HR 0.93, p=0.51). In contrast, the phase 3 monarchE trial showed improvement in iDFS with abemaciclib for 2 years with ongoing endocrine therapy compared to endocrine therapy alone (2 year iDFS rate of 92.3% versus 89.3%; HR 0.713, p=0.0009). Differences in study populations, mechanism of action of various CDK 4/6 inhibitors, dosing and drug exposure, may possibly impact results. Long-term follow-up and biomarker studies are desired to further delineate the role of CDK 4/6 inhibitors in this setting.

References:

Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, Cannady RS, Pratt-Chapman ML, Edge SB, Jacobs LA, Hurria A, Marks LB, LaMonte SJ, Warner E, Lyman GH, Ganz PA. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. 2016;34:611-35.

Ghoreishi Z, Keshavarz S, Asghari Jafarabadi M, Fathifar Z, Goodman KA, Esfahani A. Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer. BMC Cancer. 2018;18:958.

O'Shaughnessy JA, Johnston S, Harbeck N, Toi M, Im Y-H, Reinisch M, Shao Z, Kellokumpu Lehtinen PL, Huang C-S, Tryakin A, Goetz M, Rugo HS, Senkus E, Testa L, Andersson M, Tamura K, Steger GG, Del Mastro L, Cox J, Forrester T, Sherwood S, Li X, Wei R, Martin M, Rastogi P. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high risk early breast cancer. Presented at: 2020 Virtual San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract GS1-01.

Peripheral neuropathy is a well-recognized complication of taxane therapy that can impact functioning and quality of life. Dose-reductions are applied in an effort to continue treatment and minimize risk of worsening neuropathy. In a prospective analysis of breast cancer patients receiving weekly paclitaxel, Timmins et al showed neuropathy symptoms affected 85% with severe symptoms in 38%, and about half of the cohort had persistent symptoms up to 12 months post-chemotherapy. Patients who received dose reductions reported worse neuropathy and symptom burden compared to those who received full dose paclitaxel chemotherapy. It is challenging to predict with certainty which patients may experience significant neuropathy, and important to acknowledge individual patients factors such as age and other medical co-morbidities. Additional research is warranted to refine individual risk assessment as well as prevention and management strategies.

The treatment landscape for metastatic HER2-positive breast cancer is evolving at a rapid pace. Margetuximab is a chimeric antibody with similar epitope specificity to trastuzumab, but with an engineered Fc region that enhances immune activation. The phase 3 SOPHIA trial included 536 patients with pretreated HER2-positive advanced breast cancer and demonstrated modest improvement in progression free-survival with margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy (median PFS 5.8 versus 4.9 months; HR 0.76, p=0.03). The introduction of other therapies in this space (tucatinib, trastuzumab deruxtecan, neratinib) provides patients with many options, but simultaneously creates a complex treatment algorithm when it comes to therapy selection. Toxicity profiles and sites of metastases should be taken into consideration when deciding on best therapy for an individual patient.

Given the impressive outcomes seen with endocrine therapy plus CDK 4/6 inhibitors in the advanced HR+/HER2- population, these combinations are being studied in the curative setting. The phase 3 PALLAS study randomized 5,760 patients with stage I-III HR+/HER2- breast cancer to ongoing endocrine therapy with or without palbociclib for 2 years. Data from the second interim analysis of this trial showed similar invasive disease-free survival rates for the two arms (3 years iDFS 88.2% for palbociclib plus endocrine therapy versus 88.5% for endocrine therapy alone; HR 0.93, p=0.51). In contrast, the phase 3 monarchE trial showed improvement in iDFS with abemaciclib for 2 years with ongoing endocrine therapy compared to endocrine therapy alone (2 year iDFS rate of 92.3% versus 89.3%; HR 0.713, p=0.0009). Differences in study populations, mechanism of action of various CDK 4/6 inhibitors, dosing and drug exposure, may possibly impact results. Long-term follow-up and biomarker studies are desired to further delineate the role of CDK 4/6 inhibitors in this setting.

References:

Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, Cannady RS, Pratt-Chapman ML, Edge SB, Jacobs LA, Hurria A, Marks LB, LaMonte SJ, Warner E, Lyman GH, Ganz PA. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. 2016;34:611-35.

Ghoreishi Z, Keshavarz S, Asghari Jafarabadi M, Fathifar Z, Goodman KA, Esfahani A. Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer. BMC Cancer. 2018;18:958.

O'Shaughnessy JA, Johnston S, Harbeck N, Toi M, Im Y-H, Reinisch M, Shao Z, Kellokumpu Lehtinen PL, Huang C-S, Tryakin A, Goetz M, Rugo HS, Senkus E, Testa L, Andersson M, Tamura K, Steger GG, Del Mastro L, Cox J, Forrester T, Sherwood S, Li X, Wei R, Martin M, Rastogi P. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high risk early breast cancer. Presented at: 2020 Virtual San Antonio Breast Cancer Symposium; December 8-11, 2020. Abstract GS1-01.

Key clinical point: Adjuvant radiation therapy (RT) alone or in combination with endocrine therapy (ET) was associated with a lower risk for recurrence than ET alone in older women with early node-negative, human receptor-positive (HR+) breast cancer (BC). In addition, most older women with stage I HR+ breast cancers continue to receive radiation, at higher rates than patients with node-negative stage II tumors.

Major finding: Compared with ET alone, use of RT+ET (hazard ratio [HR], 0.62; P less than .0001) and RT alone (HR, 0.75; P less than .0001) was associated with a lower risk for recurrence at a median follow-up of 48 months. RT was received by 65.5% of patients, with no decrease over time. However, patients with T2 vs. T1 tumors remained less likely to receive RT (odds ratio, 0.83; P = .0024).

Study details: This study evaluated the use of adjuvant RT (n=2,046), ET (n=2,407), or RT+ET (n=4,643) after breast-conserving therapeutic surgery in older women (age at diagnosis, 66 years or more) with T1-2 node-negative, HR+ BC.

Disclosures: This study was supported by grants from the Cancer Information and Population Health Resource, UNC Lineberger Comprehensive Cancer Center, and the American Society for Radiation Oncology. Some of the study investigators reported employment and ownership in various pharmaceutical companies.

Source: Reeder-Hayes KE et al. J Geriatr Oncol. 2021 Feb 4. doi: 10.1016/j.jgo.2021.01.003.

Key clinical point: Adjuvant radiation therapy (RT) alone or in combination with endocrine therapy (ET) was associated with a lower risk for recurrence than ET alone in older women with early node-negative, human receptor-positive (HR+) breast cancer (BC). In addition, most older women with stage I HR+ breast cancers continue to receive radiation, at higher rates than patients with node-negative stage II tumors.

Major finding: Compared with ET alone, use of RT+ET (hazard ratio [HR], 0.62; P less than .0001) and RT alone (HR, 0.75; P less than .0001) was associated with a lower risk for recurrence at a median follow-up of 48 months. RT was received by 65.5% of patients, with no decrease over time. However, patients with T2 vs. T1 tumors remained less likely to receive RT (odds ratio, 0.83; P = .0024).

Study details: This study evaluated the use of adjuvant RT (n=2,046), ET (n=2,407), or RT+ET (n=4,643) after breast-conserving therapeutic surgery in older women (age at diagnosis, 66 years or more) with T1-2 node-negative, HR+ BC.

Disclosures: This study was supported by grants from the Cancer Information and Population Health Resource, UNC Lineberger Comprehensive Cancer Center, and the American Society for Radiation Oncology. Some of the study investigators reported employment and ownership in various pharmaceutical companies.

Source: Reeder-Hayes KE et al. J Geriatr Oncol. 2021 Feb 4. doi: 10.1016/j.jgo.2021.01.003.

Key clinical point: Adjuvant radiation therapy (RT) alone or in combination with endocrine therapy (ET) was associated with a lower risk for recurrence than ET alone in older women with early node-negative, human receptor-positive (HR+) breast cancer (BC). In addition, most older women with stage I HR+ breast cancers continue to receive radiation, at higher rates than patients with node-negative stage II tumors.

Major finding: Compared with ET alone, use of RT+ET (hazard ratio [HR], 0.62; P less than .0001) and RT alone (HR, 0.75; P less than .0001) was associated with a lower risk for recurrence at a median follow-up of 48 months. RT was received by 65.5% of patients, with no decrease over time. However, patients with T2 vs. T1 tumors remained less likely to receive RT (odds ratio, 0.83; P = .0024).

Study details: This study evaluated the use of adjuvant RT (n=2,046), ET (n=2,407), or RT+ET (n=4,643) after breast-conserving therapeutic surgery in older women (age at diagnosis, 66 years or more) with T1-2 node-negative, HR+ BC.

Disclosures: This study was supported by grants from the Cancer Information and Population Health Resource, UNC Lineberger Comprehensive Cancer Center, and the American Society for Radiation Oncology. Some of the study investigators reported employment and ownership in various pharmaceutical companies.

Source: Reeder-Hayes KE et al. J Geriatr Oncol. 2021 Feb 4. doi: 10.1016/j.jgo.2021.01.003.