Breast Cancer

Key clinical point: Vaginal estrogen therapy (VET) or menopausal hormone therapy (MHT) did not increase the risk for recurrence/mortality in postmenopausal women with early-stage, estrogen receptor-positive (ER+) BC; however, the recurrence risk was higher in patients receiving aromatase inhibitors (AI)+VET.

Major finding: The recurrence risk among women receiving VET (adjusted hazard ratio [aHR] 1.08; 95% CI 0.89-1.32) or MHT (aHR 1.05; 95% CI 0.62-1.78) was similar to that among never-users of hormone therapy; however, the risk was elevated in patients receiving VET+AI (aHR 1.39; 95% CI 1.04-1.85). Neither VET (aHR 0.78; 95% CI 0.71-0.87) nor MHT (aHR 0.94; 95% CI 0.70-1.26) was associated with increased overall mortality, irrespective of the receipt of AI.

Study details: Findings are from an observational cohort study including 8461 postmenopausal women with early-stage, invasive, nonmetastatic, ER+ BC who received no endocrine treatment or 5-year adjuvant endocrine therapy.

Disclosures: This study was supported by Breast Friends, a part of the Danish Cancer Society. Some authors declared receiving support, honoraria, or institutional grants from several sources.

Source: Cold S et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022 (Jul 20). Doi: 10.1093/jnci/djac112

Key clinical point: Vaginal estrogen therapy (VET) or menopausal hormone therapy (MHT) did not increase the risk for recurrence/mortality in postmenopausal women with early-stage, estrogen receptor-positive (ER+) BC; however, the recurrence risk was higher in patients receiving aromatase inhibitors (AI)+VET.

Major finding: The recurrence risk among women receiving VET (adjusted hazard ratio [aHR] 1.08; 95% CI 0.89-1.32) or MHT (aHR 1.05; 95% CI 0.62-1.78) was similar to that among never-users of hormone therapy; however, the risk was elevated in patients receiving VET+AI (aHR 1.39; 95% CI 1.04-1.85). Neither VET (aHR 0.78; 95% CI 0.71-0.87) nor MHT (aHR 0.94; 95% CI 0.70-1.26) was associated with increased overall mortality, irrespective of the receipt of AI.

Study details: Findings are from an observational cohort study including 8461 postmenopausal women with early-stage, invasive, nonmetastatic, ER+ BC who received no endocrine treatment or 5-year adjuvant endocrine therapy.

Disclosures: This study was supported by Breast Friends, a part of the Danish Cancer Society. Some authors declared receiving support, honoraria, or institutional grants from several sources.

Source: Cold S et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022 (Jul 20). Doi: 10.1093/jnci/djac112

Key clinical point: Vaginal estrogen therapy (VET) or menopausal hormone therapy (MHT) did not increase the risk for recurrence/mortality in postmenopausal women with early-stage, estrogen receptor-positive (ER+) BC; however, the recurrence risk was higher in patients receiving aromatase inhibitors (AI)+VET.

Major finding: The recurrence risk among women receiving VET (adjusted hazard ratio [aHR] 1.08; 95% CI 0.89-1.32) or MHT (aHR 1.05; 95% CI 0.62-1.78) was similar to that among never-users of hormone therapy; however, the risk was elevated in patients receiving VET+AI (aHR 1.39; 95% CI 1.04-1.85). Neither VET (aHR 0.78; 95% CI 0.71-0.87) nor MHT (aHR 0.94; 95% CI 0.70-1.26) was associated with increased overall mortality, irrespective of the receipt of AI.

Study details: Findings are from an observational cohort study including 8461 postmenopausal women with early-stage, invasive, nonmetastatic, ER+ BC who received no endocrine treatment or 5-year adjuvant endocrine therapy.

Disclosures: This study was supported by Breast Friends, a part of the Danish Cancer Society. Some authors declared receiving support, honoraria, or institutional grants from several sources.

Source: Cold S et al. Systemic or vaginal hormone therapy after early breast cancer: A Danish observational cohort study. J Natl Cancer Inst. 2022 (Jul 20). Doi: 10.1093/jnci/djac112

Key clinical point: Postmenopausal patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) who achieve a preoperative endocrine prognostic index (PEPI) score of 0-1/pathological complete response (pCR) with only neoadjuvant endocrine therapy (NET) can be safely treated without adjuvant chemotherapy.

Major finding: After a median follow-up of 60 months, the 5-year recurrence-free survival (RFS) improved significantly in patients who had PEPI 0-1/pCR without chemotherapy vs PEPI ≥2 (hazard ratio 0.18; P  =  .028). In patients who had PEPI ≥2, the 5-year RFS was similar regardless of the receipt of adjuvant chemotherapy (P  =  .432).

Study details: Findings are from a phase 2 trial including 352 postmenopausal women with early-stage, strongly ER+ and HER2− BC who received NET for 4 months before surgery; after surgery, patients with PEPI 0-1/pCR and PEPI ≥2 were recommended only adjuvant ET and adjuvant ET±chemotherapy, respectively.

Disclosures: This study was supported by Novartis. The authors declared no conflicts of interest.

Source: Wang X et al. Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study. Breast Cancer Res Treat. 2022 (Aug 2(. Doi: 10.1007/s10549-022-06686-1

Key clinical point: Postmenopausal patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) who achieve a preoperative endocrine prognostic index (PEPI) score of 0-1/pathological complete response (pCR) with only neoadjuvant endocrine therapy (NET) can be safely treated without adjuvant chemotherapy.

Major finding: After a median follow-up of 60 months, the 5-year recurrence-free survival (RFS) improved significantly in patients who had PEPI 0-1/pCR without chemotherapy vs PEPI ≥2 (hazard ratio 0.18; P  =  .028). In patients who had PEPI ≥2, the 5-year RFS was similar regardless of the receipt of adjuvant chemotherapy (P  =  .432).

Study details: Findings are from a phase 2 trial including 352 postmenopausal women with early-stage, strongly ER+ and HER2− BC who received NET for 4 months before surgery; after surgery, patients with PEPI 0-1/pCR and PEPI ≥2 were recommended only adjuvant ET and adjuvant ET±chemotherapy, respectively.

Disclosures: This study was supported by Novartis. The authors declared no conflicts of interest.

Source: Wang X et al. Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study. Breast Cancer Res Treat. 2022 (Aug 2(. Doi: 10.1007/s10549-022-06686-1

Key clinical point: Postmenopausal patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) who achieve a preoperative endocrine prognostic index (PEPI) score of 0-1/pathological complete response (pCR) with only neoadjuvant endocrine therapy (NET) can be safely treated without adjuvant chemotherapy.

Major finding: After a median follow-up of 60 months, the 5-year recurrence-free survival (RFS) improved significantly in patients who had PEPI 0-1/pCR without chemotherapy vs PEPI ≥2 (hazard ratio 0.18; P  =  .028). In patients who had PEPI ≥2, the 5-year RFS was similar regardless of the receipt of adjuvant chemotherapy (P  =  .432).

Study details: Findings are from a phase 2 trial including 352 postmenopausal women with early-stage, strongly ER+ and HER2− BC who received NET for 4 months before surgery; after surgery, patients with PEPI 0-1/pCR and PEPI ≥2 were recommended only adjuvant ET and adjuvant ET±chemotherapy, respectively.

Disclosures: This study was supported by Novartis. The authors declared no conflicts of interest.

Source: Wang X et al. Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study. Breast Cancer Res Treat. 2022 (Aug 2(. Doi: 10.1007/s10549-022-06686-1

Key clinical point: Patients with metastatic breast cancer (BC) who received oral paclitaxel plus encequidar to facilitate the absorption of oral paclitaxel showed higher confirmed tumor response compared with 3 weekly intravenous (IV) paclitaxel doses.

Major finding: Confirmed tumor response rate improved significantly with oral paclitaxel+encequidar vs IV paclitaxel (36% vs 23%; P  =  .011). The incidence of grade ≥2 neuropathy (31% vs 8%) and grade 2 alopecia (48% vs 29%) were higher with IV paclitaxel vs oral paclitaxel+encequidar; however, the incidence of grade ≥3 gastrointestinal disorders (11.7% vs 3.7%) was higher with oral paclitaxel+encequidar vs IV paclitaxel.

Study details: Findings are from the open-label, phase 3 study including 402 postmenopausal women with metastatic BC who were randomly assigned to receive oral paclitaxel+encequidar or IV paclitaxel.

Disclosures: This study was supported by Athenex, Inc. Four authors declared being employees and owning stocks in Athenex, and the other authors reported ties with several sources, including Athenex.

Source: Rugo HS et al. Open-label, randomized, multicenter, phase III study comparing oral paclitaxel plus encequidar versus intravenous paclitaxel in patients with metastatic breast cancer. J Clin Oncol. 2022 (Jul 20). Doi: 10.1200/JCO.21.02953

Key clinical point: Patients with metastatic breast cancer (BC) who received oral paclitaxel plus encequidar to facilitate the absorption of oral paclitaxel showed higher confirmed tumor response compared with 3 weekly intravenous (IV) paclitaxel doses.

Major finding: Confirmed tumor response rate improved significantly with oral paclitaxel+encequidar vs IV paclitaxel (36% vs 23%; P  =  .011). The incidence of grade ≥2 neuropathy (31% vs 8%) and grade 2 alopecia (48% vs 29%) were higher with IV paclitaxel vs oral paclitaxel+encequidar; however, the incidence of grade ≥3 gastrointestinal disorders (11.7% vs 3.7%) was higher with oral paclitaxel+encequidar vs IV paclitaxel.

Study details: Findings are from the open-label, phase 3 study including 402 postmenopausal women with metastatic BC who were randomly assigned to receive oral paclitaxel+encequidar or IV paclitaxel.

Disclosures: This study was supported by Athenex, Inc. Four authors declared being employees and owning stocks in Athenex, and the other authors reported ties with several sources, including Athenex.

Source: Rugo HS et al. Open-label, randomized, multicenter, phase III study comparing oral paclitaxel plus encequidar versus intravenous paclitaxel in patients with metastatic breast cancer. J Clin Oncol. 2022 (Jul 20). Doi: 10.1200/JCO.21.02953

Key clinical point: Patients with metastatic breast cancer (BC) who received oral paclitaxel plus encequidar to facilitate the absorption of oral paclitaxel showed higher confirmed tumor response compared with 3 weekly intravenous (IV) paclitaxel doses.

Major finding: Confirmed tumor response rate improved significantly with oral paclitaxel+encequidar vs IV paclitaxel (36% vs 23%; P  =  .011). The incidence of grade ≥2 neuropathy (31% vs 8%) and grade 2 alopecia (48% vs 29%) were higher with IV paclitaxel vs oral paclitaxel+encequidar; however, the incidence of grade ≥3 gastrointestinal disorders (11.7% vs 3.7%) was higher with oral paclitaxel+encequidar vs IV paclitaxel.

Study details: Findings are from the open-label, phase 3 study including 402 postmenopausal women with metastatic BC who were randomly assigned to receive oral paclitaxel+encequidar or IV paclitaxel.

Disclosures: This study was supported by Athenex, Inc. Four authors declared being employees and owning stocks in Athenex, and the other authors reported ties with several sources, including Athenex.

Source: Rugo HS et al. Open-label, randomized, multicenter, phase III study comparing oral paclitaxel plus encequidar versus intravenous paclitaxel in patients with metastatic breast cancer. J Clin Oncol. 2022 (Jul 20). Doi: 10.1200/JCO.21.02953

Key clinical point: Neoadjuvant atezolizumab plus docetaxel, trastuzumab, and pertuzumab (PATH) demonstrated an acceptable pathological complete response (pCR) rate and a modest safety profile in patients with human epidermal growth factor receptor 2 (ERBB2)-positive early breast cancer (BC).

Major finding: Rate of pCR was 61% in the overall cohort and was higher in patients with hormone receptor-negative vs -positive subtype (77% vs 44%), stages IIA and IIB vs stage III BC (69% and 70% vs 39% respectively), and positive vs negative programmed cell death 1 expression (100% vs 53%). Few patients reported grade ≥3 neutropenia (12%) and febrile neutropenia (8%).

Study details: Findings are from a single-arm phase 2 trial including 67 patients with ERBB2-positive stage II/III BC who initiated 6 cycles of PATH+atezolizumab every 3 weeks.

Disclosures: This study was supported by the Ministry of Health and Welfare, Republic of Korea, and other sources. The authors declared serving on advisory boards or receiving personal fees, grants, honoraria, consulting fees, or nonfinancial support from several sources.

Source: Ahn HK et al. Response rate and safety of a neoadjuvant pertuzumab, atezolizumab, docetaxel, and trastuzumab regimen for patients with ERBB2-positive stage II/III breast cancer: The neo-PATH phase 2 nonrandomized clinical trial. JAMA Oncol. 2022 (Jul 7). Doi: 10.1001/jamaoncol.2022.2310

Key clinical point: Neoadjuvant atezolizumab plus docetaxel, trastuzumab, and pertuzumab (PATH) demonstrated an acceptable pathological complete response (pCR) rate and a modest safety profile in patients with human epidermal growth factor receptor 2 (ERBB2)-positive early breast cancer (BC).

Major finding: Rate of pCR was 61% in the overall cohort and was higher in patients with hormone receptor-negative vs -positive subtype (77% vs 44%), stages IIA and IIB vs stage III BC (69% and 70% vs 39% respectively), and positive vs negative programmed cell death 1 expression (100% vs 53%). Few patients reported grade ≥3 neutropenia (12%) and febrile neutropenia (8%).

Study details: Findings are from a single-arm phase 2 trial including 67 patients with ERBB2-positive stage II/III BC who initiated 6 cycles of PATH+atezolizumab every 3 weeks.

Disclosures: This study was supported by the Ministry of Health and Welfare, Republic of Korea, and other sources. The authors declared serving on advisory boards or receiving personal fees, grants, honoraria, consulting fees, or nonfinancial support from several sources.

Source: Ahn HK et al. Response rate and safety of a neoadjuvant pertuzumab, atezolizumab, docetaxel, and trastuzumab regimen for patients with ERBB2-positive stage II/III breast cancer: The neo-PATH phase 2 nonrandomized clinical trial. JAMA Oncol. 2022 (Jul 7). Doi: 10.1001/jamaoncol.2022.2310

Key clinical point: Neoadjuvant atezolizumab plus docetaxel, trastuzumab, and pertuzumab (PATH) demonstrated an acceptable pathological complete response (pCR) rate and a modest safety profile in patients with human epidermal growth factor receptor 2 (ERBB2)-positive early breast cancer (BC).

Major finding: Rate of pCR was 61% in the overall cohort and was higher in patients with hormone receptor-negative vs -positive subtype (77% vs 44%), stages IIA and IIB vs stage III BC (69% and 70% vs 39% respectively), and positive vs negative programmed cell death 1 expression (100% vs 53%). Few patients reported grade ≥3 neutropenia (12%) and febrile neutropenia (8%).

Study details: Findings are from a single-arm phase 2 trial including 67 patients with ERBB2-positive stage II/III BC who initiated 6 cycles of PATH+atezolizumab every 3 weeks.

Disclosures: This study was supported by the Ministry of Health and Welfare, Republic of Korea, and other sources. The authors declared serving on advisory boards or receiving personal fees, grants, honoraria, consulting fees, or nonfinancial support from several sources.

Source: Ahn HK et al. Response rate and safety of a neoadjuvant pertuzumab, atezolizumab, docetaxel, and trastuzumab regimen for patients with ERBB2-positive stage II/III breast cancer: The neo-PATH phase 2 nonrandomized clinical trial. JAMA Oncol. 2022 (Jul 7). Doi: 10.1001/jamaoncol.2022.2310

Key clinical point: In patients with metastatic triple-negative breast cancer (TNBC), first-line treatment with nanoparticle albumin-bound (nab)-paclitaxel+cisplatin significantly reduced the risk for disease progression/death compared with gemcitabine+cisplatin, with both the combinations showing a consistent safety profile.

Major finding: Progression-free survival (stratified hazard ratio 0.67; P  =  .004) and objective response rate (81.1% vs 56.3%; P < .001) improved significantly in patients receiving nab-paclitaxel+cisplatin vs gemcitabine+cisplatin. Grade ≥3 only neuropathy (19% vs 0%) and nausea and vomiting (6% vs 1%) were higher in the nab-paclitaxel+cisplatin vs gemcitabine+cisplatin arm, whereas grade ≥3 thrombocytopenia (29.4% vs 3.9%) was more common in the gemcitabine+cisplatin vs nab-paclitaxel+cisplatin arm.

Study details: Findings are from an open-label phase 3 study including 254 patients with untreated metastatic TNBC who were randomly assigned to receive nab-paclitaxel+cisplatin or gemcitabine+cisplatin.

Disclosures: This study was funded by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Wang B et al. A randomized phase 3 trial of gemcitabine or nab-paclitaxel combined with cisplatin as first-line treatment in patients with metastatic triple-negative breast cancer. Nat Commun. 2022;13:4025 (Jul 12). Doi: 10.1038/s41467-022-31704-7

Key clinical point: In patients with metastatic triple-negative breast cancer (TNBC), first-line treatment with nanoparticle albumin-bound (nab)-paclitaxel+cisplatin significantly reduced the risk for disease progression/death compared with gemcitabine+cisplatin, with both the combinations showing a consistent safety profile.

Major finding: Progression-free survival (stratified hazard ratio 0.67; P  =  .004) and objective response rate (81.1% vs 56.3%; P < .001) improved significantly in patients receiving nab-paclitaxel+cisplatin vs gemcitabine+cisplatin. Grade ≥3 only neuropathy (19% vs 0%) and nausea and vomiting (6% vs 1%) were higher in the nab-paclitaxel+cisplatin vs gemcitabine+cisplatin arm, whereas grade ≥3 thrombocytopenia (29.4% vs 3.9%) was more common in the gemcitabine+cisplatin vs nab-paclitaxel+cisplatin arm.

Study details: Findings are from an open-label phase 3 study including 254 patients with untreated metastatic TNBC who were randomly assigned to receive nab-paclitaxel+cisplatin or gemcitabine+cisplatin.

Disclosures: This study was funded by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Wang B et al. A randomized phase 3 trial of gemcitabine or nab-paclitaxel combined with cisplatin as first-line treatment in patients with metastatic triple-negative breast cancer. Nat Commun. 2022;13:4025 (Jul 12). Doi: 10.1038/s41467-022-31704-7

Key clinical point: In patients with metastatic triple-negative breast cancer (TNBC), first-line treatment with nanoparticle albumin-bound (nab)-paclitaxel+cisplatin significantly reduced the risk for disease progression/death compared with gemcitabine+cisplatin, with both the combinations showing a consistent safety profile.

Major finding: Progression-free survival (stratified hazard ratio 0.67; P  =  .004) and objective response rate (81.1% vs 56.3%; P < .001) improved significantly in patients receiving nab-paclitaxel+cisplatin vs gemcitabine+cisplatin. Grade ≥3 only neuropathy (19% vs 0%) and nausea and vomiting (6% vs 1%) were higher in the nab-paclitaxel+cisplatin vs gemcitabine+cisplatin arm, whereas grade ≥3 thrombocytopenia (29.4% vs 3.9%) was more common in the gemcitabine+cisplatin vs nab-paclitaxel+cisplatin arm.

Study details: Findings are from an open-label phase 3 study including 254 patients with untreated metastatic TNBC who were randomly assigned to receive nab-paclitaxel+cisplatin or gemcitabine+cisplatin.

Disclosures: This study was funded by the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Wang B et al. A randomized phase 3 trial of gemcitabine or nab-paclitaxel combined with cisplatin as first-line treatment in patients with metastatic triple-negative breast cancer. Nat Commun. 2022;13:4025 (Jul 12). Doi: 10.1038/s41467-022-31704-7

Key clinical point: In patients with ductal carcinoma in situ (DCIS), tumor bed boost after postoperative whole breast irradiation (WBI) reduced local recurrence but with higher toxicity. Hypofractionated WBI was as effective as conventional WBI.

Major finding: The 5-year free-from-local-recurrence rates improved significantly with vs without tumor bed boost after postoperative WBI (hazard ratio 0.47; P < .001) and did not worsen with hypofractionated vs conventional WBI (P  =  .85). The rates of grade ≥2 breast pain (P  =  .003) and induration (P < .001) were higher with vs without tumor bed boost.

Study details: Findings are from a multicenter, phase 3 study including 1608 adult women with unilateral, non-low-risk DCIS who underwent breast-conserving surgery and were randomly assigned to receive WBI (conventional or hypofractionated) with or without tumor bed boost.

Disclosures: This study was funded by the National Health and Medical Research Council of Australia and other sources. Some authors declared receiving research grants, funding, or non-direct financial support from several sources.

Source: Chua BH et al. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3–07/TROG 07.01): A randomised, factorial, multicentre, open-label, phase 3 study Lancet. 2022;400(10350):431-440 (Aug 6). Doi: 10.1016/S0140-6736(22)01246-6

Key clinical point: In patients with ductal carcinoma in situ (DCIS), tumor bed boost after postoperative whole breast irradiation (WBI) reduced local recurrence but with higher toxicity. Hypofractionated WBI was as effective as conventional WBI.

Major finding: The 5-year free-from-local-recurrence rates improved significantly with vs without tumor bed boost after postoperative WBI (hazard ratio 0.47; P < .001) and did not worsen with hypofractionated vs conventional WBI (P  =  .85). The rates of grade ≥2 breast pain (P  =  .003) and induration (P < .001) were higher with vs without tumor bed boost.

Study details: Findings are from a multicenter, phase 3 study including 1608 adult women with unilateral, non-low-risk DCIS who underwent breast-conserving surgery and were randomly assigned to receive WBI (conventional or hypofractionated) with or without tumor bed boost.

Disclosures: This study was funded by the National Health and Medical Research Council of Australia and other sources. Some authors declared receiving research grants, funding, or non-direct financial support from several sources.

Source: Chua BH et al. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3–07/TROG 07.01): A randomised, factorial, multicentre, open-label, phase 3 study Lancet. 2022;400(10350):431-440 (Aug 6). Doi: 10.1016/S0140-6736(22)01246-6

Key clinical point: In patients with ductal carcinoma in situ (DCIS), tumor bed boost after postoperative whole breast irradiation (WBI) reduced local recurrence but with higher toxicity. Hypofractionated WBI was as effective as conventional WBI.

Major finding: The 5-year free-from-local-recurrence rates improved significantly with vs without tumor bed boost after postoperative WBI (hazard ratio 0.47; P < .001) and did not worsen with hypofractionated vs conventional WBI (P  =  .85). The rates of grade ≥2 breast pain (P  =  .003) and induration (P < .001) were higher with vs without tumor bed boost.

Study details: Findings are from a multicenter, phase 3 study including 1608 adult women with unilateral, non-low-risk DCIS who underwent breast-conserving surgery and were randomly assigned to receive WBI (conventional or hypofractionated) with or without tumor bed boost.

Disclosures: This study was funded by the National Health and Medical Research Council of Australia and other sources. Some authors declared receiving research grants, funding, or non-direct financial support from several sources.

Source: Chua BH et al. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3–07/TROG 07.01): A randomised, factorial, multicentre, open-label, phase 3 study Lancet. 2022;400(10350):431-440 (Aug 6). Doi: 10.1016/S0140-6736(22)01246-6

Key clinical point: First-line treatment with pembrolizumab and chemotherapy improved overall survival (OS) compared with chemotherapy alone in patients with advanced triple-negative breast cancer (TNBC) whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS) of ≥10.

Major finding: Pembrolizumab+chemotherapy vs placebo+chemotherapy improved OS in patients whose tumors expressed PD-L1 with a CPS of ≥10 (hazard ratio for death 0.73; P  =  .0185); however, no survival benefits were observed in patients with PD-L1 CPS of ≥1 (P  =  .1125). Grade ≥3 adverse events were reported by 68.1% and 66.9% of patients in the pembrolizumab+chemotherapy and placebo+chemotherapy groups, respectively.

Study details: Findings are from an interim analysis of the phase 3 KEYNOTE-355 trial including 847 patients with locally recurrent inoperable or metastatic TNBC who were randomly assigned to receive pembrolizumab+chemotherapy or placebo+chemotherapy.

Disclosures: This study was funded by Merck Sharp and Dohme. Four authors declared being employees of or owning stocks in Merck, and the other authors reported ties with several sources, including Merck.

Source: Cortes J et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387:217-226 (Jul 21). Doi: 10.1056/NEJMoa2202809

Key clinical point: First-line treatment with pembrolizumab and chemotherapy improved overall survival (OS) compared with chemotherapy alone in patients with advanced triple-negative breast cancer (TNBC) whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS) of ≥10.

Major finding: Pembrolizumab+chemotherapy vs placebo+chemotherapy improved OS in patients whose tumors expressed PD-L1 with a CPS of ≥10 (hazard ratio for death 0.73; P  =  .0185); however, no survival benefits were observed in patients with PD-L1 CPS of ≥1 (P  =  .1125). Grade ≥3 adverse events were reported by 68.1% and 66.9% of patients in the pembrolizumab+chemotherapy and placebo+chemotherapy groups, respectively.

Study details: Findings are from an interim analysis of the phase 3 KEYNOTE-355 trial including 847 patients with locally recurrent inoperable or metastatic TNBC who were randomly assigned to receive pembrolizumab+chemotherapy or placebo+chemotherapy.

Disclosures: This study was funded by Merck Sharp and Dohme. Four authors declared being employees of or owning stocks in Merck, and the other authors reported ties with several sources, including Merck.

Source: Cortes J et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387:217-226 (Jul 21). Doi: 10.1056/NEJMoa2202809

Key clinical point: First-line treatment with pembrolizumab and chemotherapy improved overall survival (OS) compared with chemotherapy alone in patients with advanced triple-negative breast cancer (TNBC) whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS) of ≥10.

Major finding: Pembrolizumab+chemotherapy vs placebo+chemotherapy improved OS in patients whose tumors expressed PD-L1 with a CPS of ≥10 (hazard ratio for death 0.73; P  =  .0185); however, no survival benefits were observed in patients with PD-L1 CPS of ≥1 (P  =  .1125). Grade ≥3 adverse events were reported by 68.1% and 66.9% of patients in the pembrolizumab+chemotherapy and placebo+chemotherapy groups, respectively.

Study details: Findings are from an interim analysis of the phase 3 KEYNOTE-355 trial including 847 patients with locally recurrent inoperable or metastatic TNBC who were randomly assigned to receive pembrolizumab+chemotherapy or placebo+chemotherapy.

Disclosures: This study was funded by Merck Sharp and Dohme. Four authors declared being employees of or owning stocks in Merck, and the other authors reported ties with several sources, including Merck.

Source: Cortes J et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387:217-226 (Jul 21). Doi: 10.1056/NEJMoa2202809

Lung disease as an adverse effect of the targeted cancer drug trastuzumab deruxtecan (T-DXd, Enhertu) is not negligible, although the benefit-to-risk relationship with use of the drug is still positive, say researchers who report a review of early clinical trials with the drug.

T-DXd is a monoclonal antibody that targets HER2. It is approved for use in HER2-positive breast, gastric, and lung cancers.

In the new study, investigators analyzed data from early clinical trials that involved patients with advanced cancers who had been heavily pretreated. They found an incidence of just over 15% for interstitial lung disease (ILD)/pneumonitis associated with the drug. Most patients (77.4%) had grade 1 or 2 ILD, but 2.2% of patients had grade 5 ILD.

“Interstitial lung disease is a known risk factor in patients treated with antibody conjugates for cancer,” commented lead author Charles Powell, MD, Icahn School of Medicine at Mount Sinai, New York. This adverse effect can lead to lung fibrosis and can become severe, life threatening, and even fatal, the authors warned.

The authors also discussed management of the event, which involves corticosteroids, and recommended that any patient who develops ILD of grade 3 or higher be hospitalized.

Close monitoring and proactive management may reduce the risk of ILD, they suggested.

Indeed, the incidence of this adverse effect was lower in a later phase 3 trial of the drug (10.5% in the DESTINY-Breast03 trial) and that the adverse events were less severe in this patient population (none of these events were of grade 4 or 5).

“Increased knowledge ... and implementation of ILD/pneumonitis monitoring, diagnosis, and management guidelines” may have resulted in this adverse effect being identified early and treated before it progressed, they commented.

ILD is highlighted in a boxed warning on the product label.

The study was published online in ESMO Open.

In their review, the investigators evaluated nine early-stage monotherapy clinical trials (phases 1 and 2) involving a total of 1,150 patients (breast cancer, 44.3%; gastric cancer, 25.6%; lung cancer, 17.7%; colorectal cancer, 9.3%, other cancers, 3.0%).

These patients had advanced cancer and had been heavily pretreated with a median of four prior lines of therapy. They received one or more doses of at least 5.4 mg/kg of T-DXd.

Nearly half of the cohort were treated for more than 6 months. A total of 276 potential ILD/pneumonitis events were sent for adjudication; of those, 85% were adjudicated as ILD/pneumonitis.

The overall incidence of adjudicated ILD/pneumonitis events was 15.4%; most were low-grade events. Some 87% of patients experienced their first ILD event within 12 months of treatment. The median time to experiencing an ILD/pneumonitis event was 5.4 months.

Some of the patients who developed grade 1 ILD/pneumonitis were treated and the adverse event resolved. These patients were then rechallenged with the drug. Only 3 of the 47 rechallenged patients experienced recurrence of ILD/pneumonitis, the authors noted.

“Rechallenge with T-DXd after complete resolution of grade 1 events is possible and warrants further investigation,” they commented. They cautioned, however, that rechallenge is not recommended for all patients, at least not for those with grade 2 or higher ILD/pneumonitis.

Overall, the authors concluded that the “benefit-risk of T-DXd treatment is positive,” but they warned that some patients may be at increased risk of developing ILD/pneumonitis

Baseline factors that increase the risk of developing an ILD/pneumonitis event include the following: being younger than 65 years, receiving a T-DXd dose of more than6.4 mg/kg, having a baseline oxygen saturation level of less than 95%, having moderate to severe renal impairment, and having lung comorbidities. In addition, patients who had initially been diagnosed with cancer more than 4 years before receiving the drug were at higher risk of developing ILD/pneumonitis.

“Using learnings from the early clinical trials experience, physician education and patient management protocols were revised and disseminated by the study sponsors [and] more recent trial data in earlier lines of therapy has demonstrated lower rates of ILD events, suggesting close monitoring and proactive management of ILD/pneumonitis is warranted for all patients,” Dr. Powell said in a statement.

The T-DXd clinical trials were sponsored by AstraZeneca and Daiichi Sankyo. Dr. Powell has received fees from Daiichi Sankyo, AstraZeneca, and Voluntis.

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

Lung disease as an adverse effect of the targeted cancer drug trastuzumab deruxtecan (T-DXd, Enhertu) is not negligible, although the benefit-to-risk relationship with use of the drug is still positive, say researchers who report a review of early clinical trials with the drug.

T-DXd is a monoclonal antibody that targets HER2. It is approved for use in HER2-positive breast, gastric, and lung cancers.

In the new study, investigators analyzed data from early clinical trials that involved patients with advanced cancers who had been heavily pretreated. They found an incidence of just over 15% for interstitial lung disease (ILD)/pneumonitis associated with the drug. Most patients (77.4%) had grade 1 or 2 ILD, but 2.2% of patients had grade 5 ILD.

“Interstitial lung disease is a known risk factor in patients treated with antibody conjugates for cancer,” commented lead author Charles Powell, MD, Icahn School of Medicine at Mount Sinai, New York. This adverse effect can lead to lung fibrosis and can become severe, life threatening, and even fatal, the authors warned.

The authors also discussed management of the event, which involves corticosteroids, and recommended that any patient who develops ILD of grade 3 or higher be hospitalized.

Close monitoring and proactive management may reduce the risk of ILD, they suggested.

Indeed, the incidence of this adverse effect was lower in a later phase 3 trial of the drug (10.5% in the DESTINY-Breast03 trial) and that the adverse events were less severe in this patient population (none of these events were of grade 4 or 5).

“Increased knowledge ... and implementation of ILD/pneumonitis monitoring, diagnosis, and management guidelines” may have resulted in this adverse effect being identified early and treated before it progressed, they commented.

ILD is highlighted in a boxed warning on the product label.

The study was published online in ESMO Open.

In their review, the investigators evaluated nine early-stage monotherapy clinical trials (phases 1 and 2) involving a total of 1,150 patients (breast cancer, 44.3%; gastric cancer, 25.6%; lung cancer, 17.7%; colorectal cancer, 9.3%, other cancers, 3.0%).

These patients had advanced cancer and had been heavily pretreated with a median of four prior lines of therapy. They received one or more doses of at least 5.4 mg/kg of T-DXd.

Nearly half of the cohort were treated for more than 6 months. A total of 276 potential ILD/pneumonitis events were sent for adjudication; of those, 85% were adjudicated as ILD/pneumonitis.

The overall incidence of adjudicated ILD/pneumonitis events was 15.4%; most were low-grade events. Some 87% of patients experienced their first ILD event within 12 months of treatment. The median time to experiencing an ILD/pneumonitis event was 5.4 months.

Some of the patients who developed grade 1 ILD/pneumonitis were treated and the adverse event resolved. These patients were then rechallenged with the drug. Only 3 of the 47 rechallenged patients experienced recurrence of ILD/pneumonitis, the authors noted.

“Rechallenge with T-DXd after complete resolution of grade 1 events is possible and warrants further investigation,” they commented. They cautioned, however, that rechallenge is not recommended for all patients, at least not for those with grade 2 or higher ILD/pneumonitis.

Overall, the authors concluded that the “benefit-risk of T-DXd treatment is positive,” but they warned that some patients may be at increased risk of developing ILD/pneumonitis

Baseline factors that increase the risk of developing an ILD/pneumonitis event include the following: being younger than 65 years, receiving a T-DXd dose of more than6.4 mg/kg, having a baseline oxygen saturation level of less than 95%, having moderate to severe renal impairment, and having lung comorbidities. In addition, patients who had initially been diagnosed with cancer more than 4 years before receiving the drug were at higher risk of developing ILD/pneumonitis.

“Using learnings from the early clinical trials experience, physician education and patient management protocols were revised and disseminated by the study sponsors [and] more recent trial data in earlier lines of therapy has demonstrated lower rates of ILD events, suggesting close monitoring and proactive management of ILD/pneumonitis is warranted for all patients,” Dr. Powell said in a statement.

The T-DXd clinical trials were sponsored by AstraZeneca and Daiichi Sankyo. Dr. Powell has received fees from Daiichi Sankyo, AstraZeneca, and Voluntis.

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

Lung disease as an adverse effect of the targeted cancer drug trastuzumab deruxtecan (T-DXd, Enhertu) is not negligible, although the benefit-to-risk relationship with use of the drug is still positive, say researchers who report a review of early clinical trials with the drug.

T-DXd is a monoclonal antibody that targets HER2. It is approved for use in HER2-positive breast, gastric, and lung cancers.

In the new study, investigators analyzed data from early clinical trials that involved patients with advanced cancers who had been heavily pretreated. They found an incidence of just over 15% for interstitial lung disease (ILD)/pneumonitis associated with the drug. Most patients (77.4%) had grade 1 or 2 ILD, but 2.2% of patients had grade 5 ILD.

“Interstitial lung disease is a known risk factor in patients treated with antibody conjugates for cancer,” commented lead author Charles Powell, MD, Icahn School of Medicine at Mount Sinai, New York. This adverse effect can lead to lung fibrosis and can become severe, life threatening, and even fatal, the authors warned.

The authors also discussed management of the event, which involves corticosteroids, and recommended that any patient who develops ILD of grade 3 or higher be hospitalized.

Close monitoring and proactive management may reduce the risk of ILD, they suggested.

Indeed, the incidence of this adverse effect was lower in a later phase 3 trial of the drug (10.5% in the DESTINY-Breast03 trial) and that the adverse events were less severe in this patient population (none of these events were of grade 4 or 5).

“Increased knowledge ... and implementation of ILD/pneumonitis monitoring, diagnosis, and management guidelines” may have resulted in this adverse effect being identified early and treated before it progressed, they commented.

ILD is highlighted in a boxed warning on the product label.

The study was published online in ESMO Open.

In their review, the investigators evaluated nine early-stage monotherapy clinical trials (phases 1 and 2) involving a total of 1,150 patients (breast cancer, 44.3%; gastric cancer, 25.6%; lung cancer, 17.7%; colorectal cancer, 9.3%, other cancers, 3.0%).

These patients had advanced cancer and had been heavily pretreated with a median of four prior lines of therapy. They received one or more doses of at least 5.4 mg/kg of T-DXd.

Nearly half of the cohort were treated for more than 6 months. A total of 276 potential ILD/pneumonitis events were sent for adjudication; of those, 85% were adjudicated as ILD/pneumonitis.

The overall incidence of adjudicated ILD/pneumonitis events was 15.4%; most were low-grade events. Some 87% of patients experienced their first ILD event within 12 months of treatment. The median time to experiencing an ILD/pneumonitis event was 5.4 months.

Some of the patients who developed grade 1 ILD/pneumonitis were treated and the adverse event resolved. These patients were then rechallenged with the drug. Only 3 of the 47 rechallenged patients experienced recurrence of ILD/pneumonitis, the authors noted.

“Rechallenge with T-DXd after complete resolution of grade 1 events is possible and warrants further investigation,” they commented. They cautioned, however, that rechallenge is not recommended for all patients, at least not for those with grade 2 or higher ILD/pneumonitis.

Overall, the authors concluded that the “benefit-risk of T-DXd treatment is positive,” but they warned that some patients may be at increased risk of developing ILD/pneumonitis

Baseline factors that increase the risk of developing an ILD/pneumonitis event include the following: being younger than 65 years, receiving a T-DXd dose of more than6.4 mg/kg, having a baseline oxygen saturation level of less than 95%, having moderate to severe renal impairment, and having lung comorbidities. In addition, patients who had initially been diagnosed with cancer more than 4 years before receiving the drug were at higher risk of developing ILD/pneumonitis.

“Using learnings from the early clinical trials experience, physician education and patient management protocols were revised and disseminated by the study sponsors [and] more recent trial data in earlier lines of therapy has demonstrated lower rates of ILD events, suggesting close monitoring and proactive management of ILD/pneumonitis is warranted for all patients,” Dr. Powell said in a statement.

The T-DXd clinical trials were sponsored by AstraZeneca and Daiichi Sankyo. Dr. Powell has received fees from Daiichi Sankyo, AstraZeneca, and Voluntis.

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

The field of radiation oncology has rapidly evolved in recent years, thanks in large part to findings from randomized clinical trials (RCTs) that have helped shift therapeutic standards, a review of the literature shows.

The authors assessed all RCTs involving radiotherapy from 2018 to 2021, with the goal of identifying the latest practice-changing data, emerging concepts, and areas that require further study.

Highlights from this research reveal how high-tech radiotherapy, such as hypofractionation and stereotactic body radiotherapy, has improved care for many patients, how personalized radiotherapy using image-based guidance has helped tailor treatments, and how endpoints that focus on quality of life and patient satisfaction are emerging.

For instance, Charles B. Simone II, MD, FACRO, who was not involved in the current work, pointed to “a proliferation of trials assessing hypofractionation in the curative setting and stereotactic body radiation therapy in the curative and poly- and oligometastatic settings that have allowed for increased patient convenience and dose intensification, respectively.”

Dr. Simone, chief medical officer, New York Proton Center, Memorial Sloan Kettering Cancer Center, also noted that the first personalized radiotherapy trials using imaging and biological markers have “the profound potential to individualize treatment and improve patient outcomes.”

The review was published in the European Journal of Cancer.
 

An evolving field

Given the fast-changing landscape for cancer therapeutics and a deluge of research studies, the authors wanted to understand the most notable advances established in recent trials as well as caveats to some approaches and emerging areas to watch.

In the review, Sophie Espenel, MD, from the department of radiation oncology, Gustave Roussy Cancer Campus, Villejuif, France, and colleagues identified 1,347 radiotherapy RCTs that were conducted from January 2018 to December 2021. Of these, the authors selected 110 large phase 2 or 3 RCTs that contained data showing practice-changing or emerging concepts.

Overall, the studies showed “great dynamism” in radiation oncology research and covered a wide range of radiotherapy practices, according to Dr. Espenel and coauthors.

A central area of research has focused on radioimmunotherapy, an approach that aims to enhance the antitumor immune response. One RCT in the preoperative setting showed, for instance, that concurrent stereotactic body radiotherapy delivered at 24 Gy over eight fractions, along with the anti–PD-L1 agent durvalumab, increased major pathologic complete response rates almost eightfold in comparison with durvalumab alone for patients with early-stage lung cancer (53.3% vs. 6.7%).

Although promising, not all trials that evaluated a concurrent chemoradiotherapy-immunotherapy strategy showed positive results. One RCT of locally advanced head and neck squamous cell carcinoma, for instance, found that median progression-free survival was not reached when adding the anti–PD-L1 avelumab to chemoradiotherapy. In addition, trials in the metastatic setting have shown conflicting results, the authors note.

Another topic of interest is that of newer radiosensitizers. A trial that evaluated high-risk locoregionally advanced head and neck squamous cell carcinoma highlighted the efficacy of xevinapant, a pro-apoptotic agent that inhibits apoptosis proteins. Xevinapant was used for the first time in conjunction with a standard high-dose cisplatin chemoradiotherapy. In this study, locoregional control at 18 months was achieved for 54% of patients who received xevinapant vs. 33% of those who received standard care. The toxicity profiles were similar.

The use of high-tech radiotherapy is gaining ground. It allows patients to receive more targeted treatments at lower doses and in shorter time frames. One trial found, for instance, that a more hypofractionated adjuvant whole breast approach, using 26 Gy in five fractions over a week, is as effective and safe as 40 Gy in 15 fractions over 3 weeks. The researchers found that there was no difference in the incidence of locoregional relapses, disease-free survival, and overall survival between the regimens.

Dr. Simone also noted that advanced treatment modalities, such as intensity-modulated radiotherapy, stereotactic radiosurgery, and proton therapy, have the potential to improve patient-reported adverse events and clinical outcomes. “I have seen this both in my clinical practice and in several recent publications,” he says.

Personalization of radiotherapy is also an emerging area that may allow for more tailored treatments with improved outcomes. The authors highlighted a study that found that PMSA PET-CT was better than conventional CT for accurately staging prostate cancer. This approach was also less expensive and led to less radiation exposure.

On the basis of this research, “PMSA PET-CT has since become the [standard of care] for prostate cancer staging,” the authors explain.

Dr. Espenel and colleagues note that as patients survive longer, quality of life and patient satisfaction are increasingly becoming endpoints in RCTs. Experts are focusing more attention on sequelae of treatments and advances in technology that can spare critical organs from radiation and reduce overall treatment time.

Shared decision-making is becoming increasingly possible in many cases as well. For example, with some clinical trials that involved different treatment modalities, outcomes were equivalent, but toxicity profiles differed, allowing patients to choose therapeutic options tailored to their preferences.

Overall, these data demonstrate “a great dynamism of radiation oncology research in most primary tumor types,” the researchers write.

The study received no outside financial support. The authors have disclosed no relevant financial relationships. Dr. Simone is chair of the American Society for Radiation Oncology Lung Resource Panel and the American Society for Radiation Oncology Veteran Affairs Radiation Oncology Quality Surveillance Blue Ribbon Lung Panel and has received honorarium from Varian Medical Systems.

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

The field of radiation oncology has rapidly evolved in recent years, thanks in large part to findings from randomized clinical trials (RCTs) that have helped shift therapeutic standards, a review of the literature shows.

The authors assessed all RCTs involving radiotherapy from 2018 to 2021, with the goal of identifying the latest practice-changing data, emerging concepts, and areas that require further study.

Highlights from this research reveal how high-tech radiotherapy, such as hypofractionation and stereotactic body radiotherapy, has improved care for many patients, how personalized radiotherapy using image-based guidance has helped tailor treatments, and how endpoints that focus on quality of life and patient satisfaction are emerging.

For instance, Charles B. Simone II, MD, FACRO, who was not involved in the current work, pointed to “a proliferation of trials assessing hypofractionation in the curative setting and stereotactic body radiation therapy in the curative and poly- and oligometastatic settings that have allowed for increased patient convenience and dose intensification, respectively.”

Dr. Simone, chief medical officer, New York Proton Center, Memorial Sloan Kettering Cancer Center, also noted that the first personalized radiotherapy trials using imaging and biological markers have “the profound potential to individualize treatment and improve patient outcomes.”

The review was published in the European Journal of Cancer.
 

An evolving field

Given the fast-changing landscape for cancer therapeutics and a deluge of research studies, the authors wanted to understand the most notable advances established in recent trials as well as caveats to some approaches and emerging areas to watch.

In the review, Sophie Espenel, MD, from the department of radiation oncology, Gustave Roussy Cancer Campus, Villejuif, France, and colleagues identified 1,347 radiotherapy RCTs that were conducted from January 2018 to December 2021. Of these, the authors selected 110 large phase 2 or 3 RCTs that contained data showing practice-changing or emerging concepts.

Overall, the studies showed “great dynamism” in radiation oncology research and covered a wide range of radiotherapy practices, according to Dr. Espenel and coauthors.

A central area of research has focused on radioimmunotherapy, an approach that aims to enhance the antitumor immune response. One RCT in the preoperative setting showed, for instance, that concurrent stereotactic body radiotherapy delivered at 24 Gy over eight fractions, along with the anti–PD-L1 agent durvalumab, increased major pathologic complete response rates almost eightfold in comparison with durvalumab alone for patients with early-stage lung cancer (53.3% vs. 6.7%).

Although promising, not all trials that evaluated a concurrent chemoradiotherapy-immunotherapy strategy showed positive results. One RCT of locally advanced head and neck squamous cell carcinoma, for instance, found that median progression-free survival was not reached when adding the anti–PD-L1 avelumab to chemoradiotherapy. In addition, trials in the metastatic setting have shown conflicting results, the authors note.

Another topic of interest is that of newer radiosensitizers. A trial that evaluated high-risk locoregionally advanced head and neck squamous cell carcinoma highlighted the efficacy of xevinapant, a pro-apoptotic agent that inhibits apoptosis proteins. Xevinapant was used for the first time in conjunction with a standard high-dose cisplatin chemoradiotherapy. In this study, locoregional control at 18 months was achieved for 54% of patients who received xevinapant vs. 33% of those who received standard care. The toxicity profiles were similar.

The use of high-tech radiotherapy is gaining ground. It allows patients to receive more targeted treatments at lower doses and in shorter time frames. One trial found, for instance, that a more hypofractionated adjuvant whole breast approach, using 26 Gy in five fractions over a week, is as effective and safe as 40 Gy in 15 fractions over 3 weeks. The researchers found that there was no difference in the incidence of locoregional relapses, disease-free survival, and overall survival between the regimens.

Dr. Simone also noted that advanced treatment modalities, such as intensity-modulated radiotherapy, stereotactic radiosurgery, and proton therapy, have the potential to improve patient-reported adverse events and clinical outcomes. “I have seen this both in my clinical practice and in several recent publications,” he says.

Personalization of radiotherapy is also an emerging area that may allow for more tailored treatments with improved outcomes. The authors highlighted a study that found that PMSA PET-CT was better than conventional CT for accurately staging prostate cancer. This approach was also less expensive and led to less radiation exposure.

On the basis of this research, “PMSA PET-CT has since become the [standard of care] for prostate cancer staging,” the authors explain.

Dr. Espenel and colleagues note that as patients survive longer, quality of life and patient satisfaction are increasingly becoming endpoints in RCTs. Experts are focusing more attention on sequelae of treatments and advances in technology that can spare critical organs from radiation and reduce overall treatment time.

Shared decision-making is becoming increasingly possible in many cases as well. For example, with some clinical trials that involved different treatment modalities, outcomes were equivalent, but toxicity profiles differed, allowing patients to choose therapeutic options tailored to their preferences.

Overall, these data demonstrate “a great dynamism of radiation oncology research in most primary tumor types,” the researchers write.

The study received no outside financial support. The authors have disclosed no relevant financial relationships. Dr. Simone is chair of the American Society for Radiation Oncology Lung Resource Panel and the American Society for Radiation Oncology Veteran Affairs Radiation Oncology Quality Surveillance Blue Ribbon Lung Panel and has received honorarium from Varian Medical Systems.

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

The field of radiation oncology has rapidly evolved in recent years, thanks in large part to findings from randomized clinical trials (RCTs) that have helped shift therapeutic standards, a review of the literature shows.

The authors assessed all RCTs involving radiotherapy from 2018 to 2021, with the goal of identifying the latest practice-changing data, emerging concepts, and areas that require further study.

Highlights from this research reveal how high-tech radiotherapy, such as hypofractionation and stereotactic body radiotherapy, has improved care for many patients, how personalized radiotherapy using image-based guidance has helped tailor treatments, and how endpoints that focus on quality of life and patient satisfaction are emerging.

For instance, Charles B. Simone II, MD, FACRO, who was not involved in the current work, pointed to “a proliferation of trials assessing hypofractionation in the curative setting and stereotactic body radiation therapy in the curative and poly- and oligometastatic settings that have allowed for increased patient convenience and dose intensification, respectively.”

Dr. Simone, chief medical officer, New York Proton Center, Memorial Sloan Kettering Cancer Center, also noted that the first personalized radiotherapy trials using imaging and biological markers have “the profound potential to individualize treatment and improve patient outcomes.”

The review was published in the European Journal of Cancer.
 

An evolving field

Given the fast-changing landscape for cancer therapeutics and a deluge of research studies, the authors wanted to understand the most notable advances established in recent trials as well as caveats to some approaches and emerging areas to watch.

In the review, Sophie Espenel, MD, from the department of radiation oncology, Gustave Roussy Cancer Campus, Villejuif, France, and colleagues identified 1,347 radiotherapy RCTs that were conducted from January 2018 to December 2021. Of these, the authors selected 110 large phase 2 or 3 RCTs that contained data showing practice-changing or emerging concepts.

Overall, the studies showed “great dynamism” in radiation oncology research and covered a wide range of radiotherapy practices, according to Dr. Espenel and coauthors.

A central area of research has focused on radioimmunotherapy, an approach that aims to enhance the antitumor immune response. One RCT in the preoperative setting showed, for instance, that concurrent stereotactic body radiotherapy delivered at 24 Gy over eight fractions, along with the anti–PD-L1 agent durvalumab, increased major pathologic complete response rates almost eightfold in comparison with durvalumab alone for patients with early-stage lung cancer (53.3% vs. 6.7%).

Although promising, not all trials that evaluated a concurrent chemoradiotherapy-immunotherapy strategy showed positive results. One RCT of locally advanced head and neck squamous cell carcinoma, for instance, found that median progression-free survival was not reached when adding the anti–PD-L1 avelumab to chemoradiotherapy. In addition, trials in the metastatic setting have shown conflicting results, the authors note.

Another topic of interest is that of newer radiosensitizers. A trial that evaluated high-risk locoregionally advanced head and neck squamous cell carcinoma highlighted the efficacy of xevinapant, a pro-apoptotic agent that inhibits apoptosis proteins. Xevinapant was used for the first time in conjunction with a standard high-dose cisplatin chemoradiotherapy. In this study, locoregional control at 18 months was achieved for 54% of patients who received xevinapant vs. 33% of those who received standard care. The toxicity profiles were similar.

The use of high-tech radiotherapy is gaining ground. It allows patients to receive more targeted treatments at lower doses and in shorter time frames. One trial found, for instance, that a more hypofractionated adjuvant whole breast approach, using 26 Gy in five fractions over a week, is as effective and safe as 40 Gy in 15 fractions over 3 weeks. The researchers found that there was no difference in the incidence of locoregional relapses, disease-free survival, and overall survival between the regimens.

Dr. Simone also noted that advanced treatment modalities, such as intensity-modulated radiotherapy, stereotactic radiosurgery, and proton therapy, have the potential to improve patient-reported adverse events and clinical outcomes. “I have seen this both in my clinical practice and in several recent publications,” he says.

Personalization of radiotherapy is also an emerging area that may allow for more tailored treatments with improved outcomes. The authors highlighted a study that found that PMSA PET-CT was better than conventional CT for accurately staging prostate cancer. This approach was also less expensive and led to less radiation exposure.

On the basis of this research, “PMSA PET-CT has since become the [standard of care] for prostate cancer staging,” the authors explain.

Dr. Espenel and colleagues note that as patients survive longer, quality of life and patient satisfaction are increasingly becoming endpoints in RCTs. Experts are focusing more attention on sequelae of treatments and advances in technology that can spare critical organs from radiation and reduce overall treatment time.

Shared decision-making is becoming increasingly possible in many cases as well. For example, with some clinical trials that involved different treatment modalities, outcomes were equivalent, but toxicity profiles differed, allowing patients to choose therapeutic options tailored to their preferences.

Overall, these data demonstrate “a great dynamism of radiation oncology research in most primary tumor types,” the researchers write.

The study received no outside financial support. The authors have disclosed no relevant financial relationships. Dr. Simone is chair of the American Society for Radiation Oncology Lung Resource Panel and the American Society for Radiation Oncology Veteran Affairs Radiation Oncology Quality Surveillance Blue Ribbon Lung Panel and has received honorarium from Varian Medical Systems.

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

The PREDICT score does not seem to be particularly accurate when it comes to estimating overall survival (OS) in patients with HER2-positive early breast cancer who are treated with modern chemotherapy and anti-HER2 targeted therapies. This is the conclusion of an international study published in the journal npj Breast Cancer. The work was supervised by Matteo Lambertini, MD, PhD, an oncologist at the IRCCS San Martino Polyclinic Hospital in Genoa, Italy.

As the authors explain, “PREDICT is a publicly available online tool that helps to predict the individual prognosis of patients with early breast cancer and to show the impact of adjuvant treatments administered after breast cancer surgery.” The tool uses traditional clinical-pathological factors. The authors also point out that the original version of this tool was validated in several datasets of patients with breast cancer. In 2011, it was updated to include HER2 status.

The investigators noted that, although the use of PREDICT is recommended to aid decision-making in the adjuvant setting, its prognostic role in patients with HER2-positive early breast cancer who are treated with modern chemotherapy and anti-HER2 therapies – even trastuzumab-based ones – remains unclear.

Therefore, they decided to analyze PREDICT’s prognostic performance using data extracted from the ALTTO trial, the largest adjuvant study ever conducted in the field of HER2-positive early breast cancer. That trial “represented a unique opportunity to investigate the reliability and prognostic performance of PREDICT in women with HER2-positive disease,” according to the investigators. They went on to specify that ALTTO evaluated adjuvant lapatinib plus trastuzumab vs. trastuzumab alone in 8,381 patients – 2,794 of whom were included in their own analysis.

What the analysis found was that, overall, PREDICT underestimated 5-year OS by 6.7%. The observed 5-year OS was 94.7%, and the predicted 5-year OS was 88.0%.

“The underestimation was consistent across all subgroups, including those according to the type of anti-HER2 therapy. The highest absolute differences were observed for patients with hormone receptor–negative disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively),” they wrote. Furthermore, they reported that “the suboptimal performance of this prognostic tool was observed irrespective of type of anti-HER2 treatment, type of chemotherapy regimen, age of the patients at the time of diagnosis, central hormone receptor status, pathological nodal status, and pathological tumor size.”

To potentially explain the reasons for the underestimation of patients’ OS, the authors questioned whether the population used to validate PREDICT accurately mirrored the real-world population of patients with HER2-positive disease treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies. “Moreover, the current standard of care for early breast cancer is even superior to the treatment received by many patients in the ALTTO study. … As such, the discordance between OS estimated by PREDICT and the current real-world OS is expected to be even higher. Therefore,” the researchers concluded, “our results suggest that the current version of PREDICT should be used with caution for prognostication in HER2-positive early breast cancer patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.”

A version of this article first appeared on Medscape.com. This article was translated from Univadis Italy.

The PREDICT score does not seem to be particularly accurate when it comes to estimating overall survival (OS) in patients with HER2-positive early breast cancer who are treated with modern chemotherapy and anti-HER2 targeted therapies. This is the conclusion of an international study published in the journal npj Breast Cancer. The work was supervised by Matteo Lambertini, MD, PhD, an oncologist at the IRCCS San Martino Polyclinic Hospital in Genoa, Italy.

As the authors explain, “PREDICT is a publicly available online tool that helps to predict the individual prognosis of patients with early breast cancer and to show the impact of adjuvant treatments administered after breast cancer surgery.” The tool uses traditional clinical-pathological factors. The authors also point out that the original version of this tool was validated in several datasets of patients with breast cancer. In 2011, it was updated to include HER2 status.

The investigators noted that, although the use of PREDICT is recommended to aid decision-making in the adjuvant setting, its prognostic role in patients with HER2-positive early breast cancer who are treated with modern chemotherapy and anti-HER2 therapies – even trastuzumab-based ones – remains unclear.

Therefore, they decided to analyze PREDICT’s prognostic performance using data extracted from the ALTTO trial, the largest adjuvant study ever conducted in the field of HER2-positive early breast cancer. That trial “represented a unique opportunity to investigate the reliability and prognostic performance of PREDICT in women with HER2-positive disease,” according to the investigators. They went on to specify that ALTTO evaluated adjuvant lapatinib plus trastuzumab vs. trastuzumab alone in 8,381 patients – 2,794 of whom were included in their own analysis.

What the analysis found was that, overall, PREDICT underestimated 5-year OS by 6.7%. The observed 5-year OS was 94.7%, and the predicted 5-year OS was 88.0%.

“The underestimation was consistent across all subgroups, including those according to the type of anti-HER2 therapy. The highest absolute differences were observed for patients with hormone receptor–negative disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively),” they wrote. Furthermore, they reported that “the suboptimal performance of this prognostic tool was observed irrespective of type of anti-HER2 treatment, type of chemotherapy regimen, age of the patients at the time of diagnosis, central hormone receptor status, pathological nodal status, and pathological tumor size.”

To potentially explain the reasons for the underestimation of patients’ OS, the authors questioned whether the population used to validate PREDICT accurately mirrored the real-world population of patients with HER2-positive disease treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies. “Moreover, the current standard of care for early breast cancer is even superior to the treatment received by many patients in the ALTTO study. … As such, the discordance between OS estimated by PREDICT and the current real-world OS is expected to be even higher. Therefore,” the researchers concluded, “our results suggest that the current version of PREDICT should be used with caution for prognostication in HER2-positive early breast cancer patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.”

A version of this article first appeared on Medscape.com. This article was translated from Univadis Italy.

The PREDICT score does not seem to be particularly accurate when it comes to estimating overall survival (OS) in patients with HER2-positive early breast cancer who are treated with modern chemotherapy and anti-HER2 targeted therapies. This is the conclusion of an international study published in the journal npj Breast Cancer. The work was supervised by Matteo Lambertini, MD, PhD, an oncologist at the IRCCS San Martino Polyclinic Hospital in Genoa, Italy.

As the authors explain, “PREDICT is a publicly available online tool that helps to predict the individual prognosis of patients with early breast cancer and to show the impact of adjuvant treatments administered after breast cancer surgery.” The tool uses traditional clinical-pathological factors. The authors also point out that the original version of this tool was validated in several datasets of patients with breast cancer. In 2011, it was updated to include HER2 status.

The investigators noted that, although the use of PREDICT is recommended to aid decision-making in the adjuvant setting, its prognostic role in patients with HER2-positive early breast cancer who are treated with modern chemotherapy and anti-HER2 therapies – even trastuzumab-based ones – remains unclear.

Therefore, they decided to analyze PREDICT’s prognostic performance using data extracted from the ALTTO trial, the largest adjuvant study ever conducted in the field of HER2-positive early breast cancer. That trial “represented a unique opportunity to investigate the reliability and prognostic performance of PREDICT in women with HER2-positive disease,” according to the investigators. They went on to specify that ALTTO evaluated adjuvant lapatinib plus trastuzumab vs. trastuzumab alone in 8,381 patients – 2,794 of whom were included in their own analysis.

What the analysis found was that, overall, PREDICT underestimated 5-year OS by 6.7%. The observed 5-year OS was 94.7%, and the predicted 5-year OS was 88.0%.

“The underestimation was consistent across all subgroups, including those according to the type of anti-HER2 therapy. The highest absolute differences were observed for patients with hormone receptor–negative disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively),” they wrote. Furthermore, they reported that “the suboptimal performance of this prognostic tool was observed irrespective of type of anti-HER2 treatment, type of chemotherapy regimen, age of the patients at the time of diagnosis, central hormone receptor status, pathological nodal status, and pathological tumor size.”

To potentially explain the reasons for the underestimation of patients’ OS, the authors questioned whether the population used to validate PREDICT accurately mirrored the real-world population of patients with HER2-positive disease treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies. “Moreover, the current standard of care for early breast cancer is even superior to the treatment received by many patients in the ALTTO study. … As such, the discordance between OS estimated by PREDICT and the current real-world OS is expected to be even higher. Therefore,” the researchers concluded, “our results suggest that the current version of PREDICT should be used with caution for prognostication in HER2-positive early breast cancer patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.”

A version of this article first appeared on Medscape.com. This article was translated from Univadis Italy.