Clinical Edge Journal Scan

Key clinical point: Bosutinib was effective and safe as a second or subsequent line of treatment in a real-life cohort of elderly patients with chronic-phase chronic myeloid leukemia (CML-CP) and multiple baseline comorbidities who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs).

Major finding: Overall, rates of cytogenic response, molecular response, 3-year event-free survival, and 3-year overall survival were 81.2%, 66.6%, 60.9%, and 86.4%, respectively. Grade 3/4 hematological and extra-hematological toxicities were reported in 6.9% and 18.8% of patients, respectively, with 11.9% of patients permanently discontinuing bosutinib because of toxicity.

Study details: Findings are from a retrospective analysis of 101 elderly (age, older than 65 years) patients with CML-CP treated with bosutinib in second or subsequent line. Patients switched to bosutinib because of intolerance (n=46) or resistance (n=55) to previous TKI therapies.

Disclosures: This study did not receive any type of funding. Some investigators including the lead author reported consulting for or receiving honoraria from various pharmaceutical companies.

Source: Latagliata R et al. Hematol Oncol. 2021 Feb 22. doi: 10.1002/hon.2851.

Key clinical point: Bosutinib was effective and safe as a second or subsequent line of treatment in a real-life cohort of elderly patients with chronic-phase chronic myeloid leukemia (CML-CP) and multiple baseline comorbidities who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs).

Major finding: Overall, rates of cytogenic response, molecular response, 3-year event-free survival, and 3-year overall survival were 81.2%, 66.6%, 60.9%, and 86.4%, respectively. Grade 3/4 hematological and extra-hematological toxicities were reported in 6.9% and 18.8% of patients, respectively, with 11.9% of patients permanently discontinuing bosutinib because of toxicity.

Study details: Findings are from a retrospective analysis of 101 elderly (age, older than 65 years) patients with CML-CP treated with bosutinib in second or subsequent line. Patients switched to bosutinib because of intolerance (n=46) or resistance (n=55) to previous TKI therapies.

Disclosures: This study did not receive any type of funding. Some investigators including the lead author reported consulting for or receiving honoraria from various pharmaceutical companies.

Source: Latagliata R et al. Hematol Oncol. 2021 Feb 22. doi: 10.1002/hon.2851.

Key clinical point: Bosutinib was effective and safe as a second or subsequent line of treatment in a real-life cohort of elderly patients with chronic-phase chronic myeloid leukemia (CML-CP) and multiple baseline comorbidities who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs).

Major finding: Overall, rates of cytogenic response, molecular response, 3-year event-free survival, and 3-year overall survival were 81.2%, 66.6%, 60.9%, and 86.4%, respectively. Grade 3/4 hematological and extra-hematological toxicities were reported in 6.9% and 18.8% of patients, respectively, with 11.9% of patients permanently discontinuing bosutinib because of toxicity.

Study details: Findings are from a retrospective analysis of 101 elderly (age, older than 65 years) patients with CML-CP treated with bosutinib in second or subsequent line. Patients switched to bosutinib because of intolerance (n=46) or resistance (n=55) to previous TKI therapies.

Disclosures: This study did not receive any type of funding. Some investigators including the lead author reported consulting for or receiving honoraria from various pharmaceutical companies.

Source: Latagliata R et al. Hematol Oncol. 2021 Feb 22. doi: 10.1002/hon.2851.

Key clinical point: Even after effective treatment with tyrosine kinase inhibitors, patients with chronic myeloid leukemia (CML) had notably altered global quality of life (QoL) and health utility scores.

Major finding: Compared with the general population, patients with CML had notably affected QoL in terms of social, role, and cognitive functioning with a mean difference of −16.0, −13.1, and −11.7, respectively. The utility score had a deviation from the reference norm of −0.15 on an average (standard deviation, 0.25) compared with the general population.

Study details: Findings are from a prospective web-based survey that assessed QoL and health utility scores in 383 patients with CML (92% in chronic-phase) in France.

Disclosures: This study was funded by the French National Agency for Research and the French Institute for Public Health Research. The authors declared no conflicts of interest.

Source: Foulon S et al. Qual Life Res. 2021 Mar 2. doi: 10.1007/s11136-021-02794-5.

Key clinical point: Even after effective treatment with tyrosine kinase inhibitors, patients with chronic myeloid leukemia (CML) had notably altered global quality of life (QoL) and health utility scores.

Major finding: Compared with the general population, patients with CML had notably affected QoL in terms of social, role, and cognitive functioning with a mean difference of −16.0, −13.1, and −11.7, respectively. The utility score had a deviation from the reference norm of −0.15 on an average (standard deviation, 0.25) compared with the general population.

Study details: Findings are from a prospective web-based survey that assessed QoL and health utility scores in 383 patients with CML (92% in chronic-phase) in France.

Disclosures: This study was funded by the French National Agency for Research and the French Institute for Public Health Research. The authors declared no conflicts of interest.

Source: Foulon S et al. Qual Life Res. 2021 Mar 2. doi: 10.1007/s11136-021-02794-5.

Key clinical point: Even after effective treatment with tyrosine kinase inhibitors, patients with chronic myeloid leukemia (CML) had notably altered global quality of life (QoL) and health utility scores.

Major finding: Compared with the general population, patients with CML had notably affected QoL in terms of social, role, and cognitive functioning with a mean difference of −16.0, −13.1, and −11.7, respectively. The utility score had a deviation from the reference norm of −0.15 on an average (standard deviation, 0.25) compared with the general population.

Study details: Findings are from a prospective web-based survey that assessed QoL and health utility scores in 383 patients with CML (92% in chronic-phase) in France.

Disclosures: This study was funded by the French National Agency for Research and the French Institute for Public Health Research. The authors declared no conflicts of interest.

Source: Foulon S et al. Qual Life Res. 2021 Mar 2. doi: 10.1007/s11136-021-02794-5.

Key clinical point: Combination of dasatinib and nivolumab was safe but did not show any clinical activity in patients with difficult-to-treat chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase (AP) who received at least 2 prior tyrosine kinase inhibitors (TKIs).

Major finding: No drug limiting toxicities were observed even with the maximum dose of both drugs. The most common grade 3 or higher adverse event (AE) of any cause was diarrhea (13%), of which only 3% were considered drug related. Serious AEs occurred in 48% of patients; however, only 2 were considered drug related. The overall response rate was low with none being durable.

Study details: Findings are from a phase 1b dose-escalation study involving 31 patients with CML in CP (n=24) or AP (n=7) who received 2 or more prior TKIs and showed progression, resistance, suboptimal response, or intolerance to the most recent therapy.

Disclosures: This trial was funded by Bristol Myers Squibb, Princeton, NJ, USA. The lead author along with other authors declared receiving grants, advisory boards, honoraria, and/or research funding from various pharmaceutical companies including Bristol Myers Squibb. R Swanink and PM Regueira were employees of Bristol Myers Squibb.

Source: Martínez-López J et al. Leuk Lymphoma. 2021 Mar 2. doi: 10.1080/10428194.2021.1889536.

Key clinical point: Combination of dasatinib and nivolumab was safe but did not show any clinical activity in patients with difficult-to-treat chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase (AP) who received at least 2 prior tyrosine kinase inhibitors (TKIs).

Major finding: No drug limiting toxicities were observed even with the maximum dose of both drugs. The most common grade 3 or higher adverse event (AE) of any cause was diarrhea (13%), of which only 3% were considered drug related. Serious AEs occurred in 48% of patients; however, only 2 were considered drug related. The overall response rate was low with none being durable.

Study details: Findings are from a phase 1b dose-escalation study involving 31 patients with CML in CP (n=24) or AP (n=7) who received 2 or more prior TKIs and showed progression, resistance, suboptimal response, or intolerance to the most recent therapy.

Disclosures: This trial was funded by Bristol Myers Squibb, Princeton, NJ, USA. The lead author along with other authors declared receiving grants, advisory boards, honoraria, and/or research funding from various pharmaceutical companies including Bristol Myers Squibb. R Swanink and PM Regueira were employees of Bristol Myers Squibb.

Source: Martínez-López J et al. Leuk Lymphoma. 2021 Mar 2. doi: 10.1080/10428194.2021.1889536.

Key clinical point: Combination of dasatinib and nivolumab was safe but did not show any clinical activity in patients with difficult-to-treat chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase (AP) who received at least 2 prior tyrosine kinase inhibitors (TKIs).

Major finding: No drug limiting toxicities were observed even with the maximum dose of both drugs. The most common grade 3 or higher adverse event (AE) of any cause was diarrhea (13%), of which only 3% were considered drug related. Serious AEs occurred in 48% of patients; however, only 2 were considered drug related. The overall response rate was low with none being durable.

Study details: Findings are from a phase 1b dose-escalation study involving 31 patients with CML in CP (n=24) or AP (n=7) who received 2 or more prior TKIs and showed progression, resistance, suboptimal response, or intolerance to the most recent therapy.

Disclosures: This trial was funded by Bristol Myers Squibb, Princeton, NJ, USA. The lead author along with other authors declared receiving grants, advisory boards, honoraria, and/or research funding from various pharmaceutical companies including Bristol Myers Squibb. R Swanink and PM Regueira were employees of Bristol Myers Squibb.

Source: Martínez-López J et al. Leuk Lymphoma. 2021 Mar 2. doi: 10.1080/10428194.2021.1889536.

Key clinical point: Imatinib treatment following interferon-α failure showed long-term efficacy in a real-life setting of patients with late chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: After a median of 4.5 months of therapy initiation, 84% of patients achieved complete cytogenic response as their best cytogenetic response. The estimated 18-year overall survival, event-free survival, and progression-free survival were 64.8%, 69%, and 64.4%, respectively. Imatinib discontinuation and CML-related deaths occurred in 36% and 34% of patients, respectively, and 86% of patients were in treatment-free remission at the last follow-up.

Study details: Findings are from a retrospective analysis of 139 patients with late CML-CP treated with imatinib following interferon-α therapy failure followed up for a median of 16.6 years.

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

Source: Pepe S et al. Leuk Lymphoma. 2021 Mar 16. doi: 10.1080/10428194.2021.1901094.

Key clinical point: Imatinib treatment following interferon-α failure showed long-term efficacy in a real-life setting of patients with late chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: After a median of 4.5 months of therapy initiation, 84% of patients achieved complete cytogenic response as their best cytogenetic response. The estimated 18-year overall survival, event-free survival, and progression-free survival were 64.8%, 69%, and 64.4%, respectively. Imatinib discontinuation and CML-related deaths occurred in 36% and 34% of patients, respectively, and 86% of patients were in treatment-free remission at the last follow-up.

Study details: Findings are from a retrospective analysis of 139 patients with late CML-CP treated with imatinib following interferon-α therapy failure followed up for a median of 16.6 years.

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

Source: Pepe S et al. Leuk Lymphoma. 2021 Mar 16. doi: 10.1080/10428194.2021.1901094.

Key clinical point: Imatinib treatment following interferon-α failure showed long-term efficacy in a real-life setting of patients with late chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: After a median of 4.5 months of therapy initiation, 84% of patients achieved complete cytogenic response as their best cytogenetic response. The estimated 18-year overall survival, event-free survival, and progression-free survival were 64.8%, 69%, and 64.4%, respectively. Imatinib discontinuation and CML-related deaths occurred in 36% and 34% of patients, respectively, and 86% of patients were in treatment-free remission at the last follow-up.

Study details: Findings are from a retrospective analysis of 139 patients with late CML-CP treated with imatinib following interferon-α therapy failure followed up for a median of 16.6 years.

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

Source: Pepe S et al. Leuk Lymphoma. 2021 Mar 16. doi: 10.1080/10428194.2021.1901094.

Key clinical point: Dasatinib and nilotinib as second-line treatments were equally effective, with a high molecular response (MR) and a tolerable safety profile in real-life patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 12 months, 47% and 38% of patients had a major MR and 18.2% and 16.6% had a deep MR in the dasatinib and nilotinib groups, respectively (P = .481). Grade 3-4 adverse events were more frequent in dasatinib vs. nilotinib groups (P = .003) with no effect on MR.

Study details: Findings are from a retrospective analysis of 131 patients with CML-CP who switched to second-line treatment with either dasatinib (n=72) or nilotinib (n=59) after frontline imatinib intolerance/resistance.

Disclosures: The authors did not declare any source of funding. M Breccia, M Martelli, and F Efficace reported receiving honoraria, personal fees, and grants from and being on the advisory board for various pharmaceutical companies. Other authors had no disclosures.

Source: Scalzulli E et al. Ann Hematol. 2021 Mar 7. doi: 10.1007/s00277-021-04477-0.

Key clinical point: Dasatinib and nilotinib as second-line treatments were equally effective, with a high molecular response (MR) and a tolerable safety profile in real-life patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 12 months, 47% and 38% of patients had a major MR and 18.2% and 16.6% had a deep MR in the dasatinib and nilotinib groups, respectively (P = .481). Grade 3-4 adverse events were more frequent in dasatinib vs. nilotinib groups (P = .003) with no effect on MR.

Study details: Findings are from a retrospective analysis of 131 patients with CML-CP who switched to second-line treatment with either dasatinib (n=72) or nilotinib (n=59) after frontline imatinib intolerance/resistance.

Disclosures: The authors did not declare any source of funding. M Breccia, M Martelli, and F Efficace reported receiving honoraria, personal fees, and grants from and being on the advisory board for various pharmaceutical companies. Other authors had no disclosures.

Source: Scalzulli E et al. Ann Hematol. 2021 Mar 7. doi: 10.1007/s00277-021-04477-0.

Key clinical point: Dasatinib and nilotinib as second-line treatments were equally effective, with a high molecular response (MR) and a tolerable safety profile in real-life patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: At 12 months, 47% and 38% of patients had a major MR and 18.2% and 16.6% had a deep MR in the dasatinib and nilotinib groups, respectively (P = .481). Grade 3-4 adverse events were more frequent in dasatinib vs. nilotinib groups (P = .003) with no effect on MR.

Study details: Findings are from a retrospective analysis of 131 patients with CML-CP who switched to second-line treatment with either dasatinib (n=72) or nilotinib (n=59) after frontline imatinib intolerance/resistance.

Disclosures: The authors did not declare any source of funding. M Breccia, M Martelli, and F Efficace reported receiving honoraria, personal fees, and grants from and being on the advisory board for various pharmaceutical companies. Other authors had no disclosures.

Source: Scalzulli E et al. Ann Hematol. 2021 Mar 7. doi: 10.1007/s00277-021-04477-0.

Key clinical point: More than 3 years of frontline nilotinib treatment was effective with sustained long-term high treatment-free remission (TFR) rates and manageable safety in patients with Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Among patients who entered TFR, 41.6% remained in major molecular response (MMR), with 40.0% in MR^4.5, whereas 98.9% of patients who lost MMR regained after treatment reinitiation. No disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously.

Study details: Findings are from a 5-year follow-up of phase 2 ENESTfreedom trial including 190 adult patients with Ph+ CML-CP who received at least 2 years of frontline nilotinib treatment, achieved MR^4.5, and attempted TFR after undergoing a 1-year nilotinib treatment consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author along with other authors reported ties with various pharmaceutical companies including Novartis. P Aimone, S Li, and K Titorenko reported being employees of Novartis.

Source: Radich JP et al. Leukemia. 2021 Mar 11. doi: 10.1038/s41375-021-01205-5.

Key clinical point: More than 3 years of frontline nilotinib treatment was effective with sustained long-term high treatment-free remission (TFR) rates and manageable safety in patients with Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Among patients who entered TFR, 41.6% remained in major molecular response (MMR), with 40.0% in MR^4.5, whereas 98.9% of patients who lost MMR regained after treatment reinitiation. No disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously.

Study details: Findings are from a 5-year follow-up of phase 2 ENESTfreedom trial including 190 adult patients with Ph+ CML-CP who received at least 2 years of frontline nilotinib treatment, achieved MR^4.5, and attempted TFR after undergoing a 1-year nilotinib treatment consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author along with other authors reported ties with various pharmaceutical companies including Novartis. P Aimone, S Li, and K Titorenko reported being employees of Novartis.

Source: Radich JP et al. Leukemia. 2021 Mar 11. doi: 10.1038/s41375-021-01205-5.

Key clinical point: More than 3 years of frontline nilotinib treatment was effective with sustained long-term high treatment-free remission (TFR) rates and manageable safety in patients with Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Among patients who entered TFR, 41.6% remained in major molecular response (MMR), with 40.0% in MR^4.5, whereas 98.9% of patients who lost MMR regained after treatment reinitiation. No disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously.

Study details: Findings are from a 5-year follow-up of phase 2 ENESTfreedom trial including 190 adult patients with Ph+ CML-CP who received at least 2 years of frontline nilotinib treatment, achieved MR^4.5, and attempted TFR after undergoing a 1-year nilotinib treatment consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author along with other authors reported ties with various pharmaceutical companies including Novartis. P Aimone, S Li, and K Titorenko reported being employees of Novartis.

Source: Radich JP et al. Leukemia. 2021 Mar 11. doi: 10.1038/s41375-021-01205-5.

Key clinical point: Initial rate of BCR-ABL1 decline, measured as halving time, was a strong predictor of sustained treatment-free remission (TFR) post-tyrosine kinase inhibitor (TKI) cessation in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with firstline TKI therapies.

Major finding: Patients with a sustained TFR had a shorter BCR-ABL1 halving time vs. those with molecular relapse (10.1 vs. 21.7 days; P less than .001). The probability of sustained TFR was 80% vs. 4% among patients with halving time less than 9.35 days vs. more than 21.85 days (P less than .001).

Study details: Findings are from a retrospective analysis of 115 adult patients with CML-CP who attempted TFR and were followed up for at least 12 months post-TKI discontinuation.

Disclosures: The authors did not declare any source of funding. Some of the investigators including the lead author reported receiving honoraria and travel and accommodation expenses; being on the advisory board; and receiving research funding from various pharmaceutical companies.

Source: Shanmuganathan N et al. Blood. 2021 Mar 4. doi: 10.1182/blood.2020005514.

Key clinical point: Initial rate of BCR-ABL1 decline, measured as halving time, was a strong predictor of sustained treatment-free remission (TFR) post-tyrosine kinase inhibitor (TKI) cessation in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with firstline TKI therapies.

Major finding: Patients with a sustained TFR had a shorter BCR-ABL1 halving time vs. those with molecular relapse (10.1 vs. 21.7 days; P less than .001). The probability of sustained TFR was 80% vs. 4% among patients with halving time less than 9.35 days vs. more than 21.85 days (P less than .001).

Study details: Findings are from a retrospective analysis of 115 adult patients with CML-CP who attempted TFR and were followed up for at least 12 months post-TKI discontinuation.

Disclosures: The authors did not declare any source of funding. Some of the investigators including the lead author reported receiving honoraria and travel and accommodation expenses; being on the advisory board; and receiving research funding from various pharmaceutical companies.

Source: Shanmuganathan N et al. Blood. 2021 Mar 4. doi: 10.1182/blood.2020005514.

Key clinical point: Initial rate of BCR-ABL1 decline, measured as halving time, was a strong predictor of sustained treatment-free remission (TFR) post-tyrosine kinase inhibitor (TKI) cessation in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with firstline TKI therapies.

Major finding: Patients with a sustained TFR had a shorter BCR-ABL1 halving time vs. those with molecular relapse (10.1 vs. 21.7 days; P less than .001). The probability of sustained TFR was 80% vs. 4% among patients with halving time less than 9.35 days vs. more than 21.85 days (P less than .001).

Study details: Findings are from a retrospective analysis of 115 adult patients with CML-CP who attempted TFR and were followed up for at least 12 months post-TKI discontinuation.

Disclosures: The authors did not declare any source of funding. Some of the investigators including the lead author reported receiving honoraria and travel and accommodation expenses; being on the advisory board; and receiving research funding from various pharmaceutical companies.

Source: Shanmuganathan N et al. Blood. 2021 Mar 4. doi: 10.1182/blood.2020005514.

Key clinical point: High red blood cell distribution width (RDW) at diagnosis was associated with poor prognosis and treatment response in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs).

Major finding: High RDW was a significant predictor of poor overall survival (hazard ratio, [HR], 9.741; P = .005) and progression-free survival (HR, 16.74; P = .009). Patients with high RDW had worse treatment responses at 3 months (P = .03) and 6 months (P = .02).

Study details: Findings are from a retrospective analysis of 93 patients with newly diagnosed CML-CP and treated with TKIs. Patients were categorized into low (18.65% or lesser; n=58) and high (more than 18.65%; n=35) RDW groups.

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

Source: Mao XL et al. Medicine. 2021 Mar 12. doi: 10.1097/MD.0000000000024003.

Key clinical point: High red blood cell distribution width (RDW) at diagnosis was associated with poor prognosis and treatment response in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs).

Major finding: High RDW was a significant predictor of poor overall survival (hazard ratio, [HR], 9.741; P = .005) and progression-free survival (HR, 16.74; P = .009). Patients with high RDW had worse treatment responses at 3 months (P = .03) and 6 months (P = .02).

Study details: Findings are from a retrospective analysis of 93 patients with newly diagnosed CML-CP and treated with TKIs. Patients were categorized into low (18.65% or lesser; n=58) and high (more than 18.65%; n=35) RDW groups.

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

Source: Mao XL et al. Medicine. 2021 Mar 12. doi: 10.1097/MD.0000000000024003.

Key clinical point: High red blood cell distribution width (RDW) at diagnosis was associated with poor prognosis and treatment response in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs).

Major finding: High RDW was a significant predictor of poor overall survival (hazard ratio, [HR], 9.741; P = .005) and progression-free survival (HR, 16.74; P = .009). Patients with high RDW had worse treatment responses at 3 months (P = .03) and 6 months (P = .02).

Study details: Findings are from a retrospective analysis of 93 patients with newly diagnosed CML-CP and treated with TKIs. Patients were categorized into low (18.65% or lesser; n=58) and high (more than 18.65%; n=35) RDW groups.

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

Source: Mao XL et al. Medicine. 2021 Mar 12. doi: 10.1097/MD.0000000000024003.

Adjuvant endocrine therapy (ET) has been shown to reduce risk of recurrence and improve survival in HR+ early breast cancer (EBC). A retrospective matched cohort analysis of 1,972 patients ≥70 years of age with HR+/HER2-negative, node-negative EBC and multiple medical co-morbidities, demonstrated higher median overall survival (OS) in patients who received ET versus those who did not (79.2 months compared to 67.7 months, p<0.0001). Older women with multiple medical co-morbidities may be at greater risk of toxicities related to ET, which can impact quality of life and adherence. The probability of initiating ET has been shown to be greater among patients who underwent radiation, thus highlighting the need to identify those who will adhere to ET when making decisions regarding radiation therapy to optimize care. ET should be discussed with all women who are candidates for this therapy, with a focus on individualized benefit and risk of these agents.

Studies of immunotherapy in metastatic triple-negative breast cancer have shown promising results, notably in patients with PD-L1 enriched tumors (IMpassion 130 and KEYNOTE-355). KEYNOTE-119 was a phase 3 study including 1,098 patients with metastatic TNBC who had received one or two previous systemic therapies for metastatic disease and progressed on most recent treatment, with randomization to pembrolizumab or physician’s choice chemotherapy . Median OS for pembrolizumab compared to chemotherapy was similar in the overall population (9.9 months versus 10.8 months, HR 0.97) and in patients with PD-L1 CPS score of ≥10 (12.7 months versus 11.6 months, HR 0.78, p=0.057). Although not statistically significant, greater PD-L1 expression was associated with longer median OS with pembrolizumab. Responses to immunotherapy may be durable in select patients, and these agents have an overall favorable toxicity profile. Novel immunotherapy combinations as well as biomarkers to predict response are certainly desired in this space.

Combination endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for metastatic HR+/HER2-negative breast cancer. Neutropenia is a common adverse event (AE) seen with the CDK 4/6 inhibitor palbociclib, and dosing guidelines provide a clear algorithm for drug monitoring and adjustment for cytopenias. Cutaneous toxicities, although not commonly seen, have been reported in the literature. Chawla and colleagues performed a retrospective analysis including 324 patients with advanced HR+/HER2-negative breast cancer who received palbociclib plus endocrine therapy. Cutaneous AEs were seen in 14.2%, with a significant proportion occurring early (41% occurred during or after the first cycle) and 50% resolved within 14 days (average 43 days). Of those who developed cutaneous AEs (n=46), only 15% and 4% required temporary hold and permanent cessation of therapy, respectively. These findings indicate a low overall incidence of cutaneous AEs associated with palbociclib, however highlight the importance of prompt recognition, management, and dermatology referral as appropriate, to help maintain patients on effective cancer-directed therapy.

References:

Yau C, van der Noordaa M, Wei J, et al. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: a multi-center pooled analysis. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS5-01.

Wei M, Wang X, Zimmerman DN, Burt LM, Haaland B, Henry NL. Endocrine therapy and radiotherapy use among older women with hormone receptor-positive, clinically node-negative breast cancer. Breast Cancer Res Treat. 2021 Jan 9. doi: 10.1007/s10549-020-06071-w.Epub ahead of print.

Emens LA, Adams S, Barrios CH, et al. IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab plus nabpaclitaxel versus placebo plus nabpaclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. Presented at: ESMO Virtual Congress 2020, Ann Oncol. 2020;31S:ESMO #LBA16.

Khan NAJ, Alsharedi M. Bullous Skin Rash: A Rare Case of Palbociclib-Induced Dermatological Toxicity. Cureus. 2020 Sep 3;12(9):e10229. doi: 10.7759/cureus.10229.

Adjuvant endocrine therapy (ET) has been shown to reduce risk of recurrence and improve survival in HR+ early breast cancer (EBC). A retrospective matched cohort analysis of 1,972 patients ≥70 years of age with HR+/HER2-negative, node-negative EBC and multiple medical co-morbidities, demonstrated higher median overall survival (OS) in patients who received ET versus those who did not (79.2 months compared to 67.7 months, p<0.0001). Older women with multiple medical co-morbidities may be at greater risk of toxicities related to ET, which can impact quality of life and adherence. The probability of initiating ET has been shown to be greater among patients who underwent radiation, thus highlighting the need to identify those who will adhere to ET when making decisions regarding radiation therapy to optimize care. ET should be discussed with all women who are candidates for this therapy, with a focus on individualized benefit and risk of these agents.

Studies of immunotherapy in metastatic triple-negative breast cancer have shown promising results, notably in patients with PD-L1 enriched tumors (IMpassion 130 and KEYNOTE-355). KEYNOTE-119 was a phase 3 study including 1,098 patients with metastatic TNBC who had received one or two previous systemic therapies for metastatic disease and progressed on most recent treatment, with randomization to pembrolizumab or physician’s choice chemotherapy . Median OS for pembrolizumab compared to chemotherapy was similar in the overall population (9.9 months versus 10.8 months, HR 0.97) and in patients with PD-L1 CPS score of ≥10 (12.7 months versus 11.6 months, HR 0.78, p=0.057). Although not statistically significant, greater PD-L1 expression was associated with longer median OS with pembrolizumab. Responses to immunotherapy may be durable in select patients, and these agents have an overall favorable toxicity profile. Novel immunotherapy combinations as well as biomarkers to predict response are certainly desired in this space.

Combination endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for metastatic HR+/HER2-negative breast cancer. Neutropenia is a common adverse event (AE) seen with the CDK 4/6 inhibitor palbociclib, and dosing guidelines provide a clear algorithm for drug monitoring and adjustment for cytopenias. Cutaneous toxicities, although not commonly seen, have been reported in the literature. Chawla and colleagues performed a retrospective analysis including 324 patients with advanced HR+/HER2-negative breast cancer who received palbociclib plus endocrine therapy. Cutaneous AEs were seen in 14.2%, with a significant proportion occurring early (41% occurred during or after the first cycle) and 50% resolved within 14 days (average 43 days). Of those who developed cutaneous AEs (n=46), only 15% and 4% required temporary hold and permanent cessation of therapy, respectively. These findings indicate a low overall incidence of cutaneous AEs associated with palbociclib, however highlight the importance of prompt recognition, management, and dermatology referral as appropriate, to help maintain patients on effective cancer-directed therapy.

References:

Yau C, van der Noordaa M, Wei J, et al. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: a multi-center pooled analysis. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS5-01.

Wei M, Wang X, Zimmerman DN, Burt LM, Haaland B, Henry NL. Endocrine therapy and radiotherapy use among older women with hormone receptor-positive, clinically node-negative breast cancer. Breast Cancer Res Treat. 2021 Jan 9. doi: 10.1007/s10549-020-06071-w.Epub ahead of print.

Emens LA, Adams S, Barrios CH, et al. IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab plus nabpaclitaxel versus placebo plus nabpaclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. Presented at: ESMO Virtual Congress 2020, Ann Oncol. 2020;31S:ESMO #LBA16.

Khan NAJ, Alsharedi M. Bullous Skin Rash: A Rare Case of Palbociclib-Induced Dermatological Toxicity. Cureus. 2020 Sep 3;12(9):e10229. doi: 10.7759/cureus.10229.

Adjuvant endocrine therapy (ET) has been shown to reduce risk of recurrence and improve survival in HR+ early breast cancer (EBC). A retrospective matched cohort analysis of 1,972 patients ≥70 years of age with HR+/HER2-negative, node-negative EBC and multiple medical co-morbidities, demonstrated higher median overall survival (OS) in patients who received ET versus those who did not (79.2 months compared to 67.7 months, p<0.0001). Older women with multiple medical co-morbidities may be at greater risk of toxicities related to ET, which can impact quality of life and adherence. The probability of initiating ET has been shown to be greater among patients who underwent radiation, thus highlighting the need to identify those who will adhere to ET when making decisions regarding radiation therapy to optimize care. ET should be discussed with all women who are candidates for this therapy, with a focus on individualized benefit and risk of these agents.

Studies of immunotherapy in metastatic triple-negative breast cancer have shown promising results, notably in patients with PD-L1 enriched tumors (IMpassion 130 and KEYNOTE-355). KEYNOTE-119 was a phase 3 study including 1,098 patients with metastatic TNBC who had received one or two previous systemic therapies for metastatic disease and progressed on most recent treatment, with randomization to pembrolizumab or physician’s choice chemotherapy . Median OS for pembrolizumab compared to chemotherapy was similar in the overall population (9.9 months versus 10.8 months, HR 0.97) and in patients with PD-L1 CPS score of ≥10 (12.7 months versus 11.6 months, HR 0.78, p=0.057). Although not statistically significant, greater PD-L1 expression was associated with longer median OS with pembrolizumab. Responses to immunotherapy may be durable in select patients, and these agents have an overall favorable toxicity profile. Novel immunotherapy combinations as well as biomarkers to predict response are certainly desired in this space.

Combination endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for metastatic HR+/HER2-negative breast cancer. Neutropenia is a common adverse event (AE) seen with the CDK 4/6 inhibitor palbociclib, and dosing guidelines provide a clear algorithm for drug monitoring and adjustment for cytopenias. Cutaneous toxicities, although not commonly seen, have been reported in the literature. Chawla and colleagues performed a retrospective analysis including 324 patients with advanced HR+/HER2-negative breast cancer who received palbociclib plus endocrine therapy. Cutaneous AEs were seen in 14.2%, with a significant proportion occurring early (41% occurred during or after the first cycle) and 50% resolved within 14 days (average 43 days). Of those who developed cutaneous AEs (n=46), only 15% and 4% required temporary hold and permanent cessation of therapy, respectively. These findings indicate a low overall incidence of cutaneous AEs associated with palbociclib, however highlight the importance of prompt recognition, management, and dermatology referral as appropriate, to help maintain patients on effective cancer-directed therapy.

References:

Yau C, van der Noordaa M, Wei J, et al. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: a multi-center pooled analysis. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS5-01.

Wei M, Wang X, Zimmerman DN, Burt LM, Haaland B, Henry NL. Endocrine therapy and radiotherapy use among older women with hormone receptor-positive, clinically node-negative breast cancer. Breast Cancer Res Treat. 2021 Jan 9. doi: 10.1007/s10549-020-06071-w.Epub ahead of print.

Emens LA, Adams S, Barrios CH, et al. IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab plus nabpaclitaxel versus placebo plus nabpaclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. Presented at: ESMO Virtual Congress 2020, Ann Oncol. 2020;31S:ESMO #LBA16.

Khan NAJ, Alsharedi M. Bullous Skin Rash: A Rare Case of Palbociclib-Induced Dermatological Toxicity. Cureus. 2020 Sep 3;12(9):e10229. doi: 10.7759/cureus.10229.

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who achieved a pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and chemotherapy (nPTC) and then received adjuvant trastuzumab remained at risk for recurrence, indicating the need for alternative therapies.

Major finding: At 4 years, the invasive disease-free survival rates for the overall, node-positive, and node-negative cohorts were 90.0% (95% confidence interval [CI], 84.6%-93.6%), 86.2% (95% CI, 78.1%-91.4%), and 96.0% (95% CI, 88.0%-98.7%), respectively.

Study details: Findings are from a real-world, retrospective analysis of 217 patients with HER2+ locally advanced, high-risk early-stage BC, including 135 patients with node-positive and 77 with node-negative disease. Patients received nPTC, had pCR, and then received adjuvant trastuzumab.

Disclosures: This study was funded by Genentech, Inc. Some investigators including the lead author reported ties with various pharmaceutical companies, including Genentech. J Sussell, A Cheng, and A Fung declared being employees of Genentech, Inc.

Source: O’Shaughnessy J et al. Breast Cancer Res Treat. 2021 Mar 1. doi: 10.1007/s10549-021-06137-3.

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who achieved a pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and chemotherapy (nPTC) and then received adjuvant trastuzumab remained at risk for recurrence, indicating the need for alternative therapies.

Major finding: At 4 years, the invasive disease-free survival rates for the overall, node-positive, and node-negative cohorts were 90.0% (95% confidence interval [CI], 84.6%-93.6%), 86.2% (95% CI, 78.1%-91.4%), and 96.0% (95% CI, 88.0%-98.7%), respectively.

Study details: Findings are from a real-world, retrospective analysis of 217 patients with HER2+ locally advanced, high-risk early-stage BC, including 135 patients with node-positive and 77 with node-negative disease. Patients received nPTC, had pCR, and then received adjuvant trastuzumab.

Disclosures: This study was funded by Genentech, Inc. Some investigators including the lead author reported ties with various pharmaceutical companies, including Genentech. J Sussell, A Cheng, and A Fung declared being employees of Genentech, Inc.

Source: O’Shaughnessy J et al. Breast Cancer Res Treat. 2021 Mar 1. doi: 10.1007/s10549-021-06137-3.

Key clinical point: Patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who achieved a pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and chemotherapy (nPTC) and then received adjuvant trastuzumab remained at risk for recurrence, indicating the need for alternative therapies.

Major finding: At 4 years, the invasive disease-free survival rates for the overall, node-positive, and node-negative cohorts were 90.0% (95% confidence interval [CI], 84.6%-93.6%), 86.2% (95% CI, 78.1%-91.4%), and 96.0% (95% CI, 88.0%-98.7%), respectively.

Study details: Findings are from a real-world, retrospective analysis of 217 patients with HER2+ locally advanced, high-risk early-stage BC, including 135 patients with node-positive and 77 with node-negative disease. Patients received nPTC, had pCR, and then received adjuvant trastuzumab.

Disclosures: This study was funded by Genentech, Inc. Some investigators including the lead author reported ties with various pharmaceutical companies, including Genentech. J Sussell, A Cheng, and A Fung declared being employees of Genentech, Inc.

Source: O’Shaughnessy J et al. Breast Cancer Res Treat. 2021 Mar 1. doi: 10.1007/s10549-021-06137-3.