Post San Antonio 2024 update: chemotherapy, immunotherapy and management of side effects
- Open Access
- 03.09.2025
- short review
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Summary
Review
At the 47th San Antonio Breast Cancer Symposium several studies aimed at defining optimal (neo)adjuvant chemotherapy for patients with luminal breast cancer. Additionally, new findings on immune checkpoint inhibitors for early triple-negative breast cancer (TNBC) were presented, and olanzapine was confirmed as an effective treatment for refractory chemotherapy-induced nausea. The most important studies on chemotherapy, immunotherapy, and side effect management presented at the symposium are summarized in this article.
Chemotherapy
Chen et al. (GS3-03): TAILORx—anthracyclines in patients with high genomic risk [1]
A post hoc analysis of the TAILORx study examined which patients with node-negative HR+/HER2 breast cancer benefit from adjuvant anthracycline-containing chemotherapy. In TAILORx over 10,000 patients were treated based on the Oncotype DX Recurrence Score (RS) with or without adjuvant chemotherapy. Both anthracycline-containing and anthracycline-free regimens were allowed. The analysis included 2549 patients with a RS > 11, who received chemotherapy, either docetaxel/cyclophosphamide (TC; n = 2111) or doxorubicin, cyclophosphamide, and a taxane (T-AC; sequential or concurrent; n = 438). Patients receiving anthracyclines had slightly more risk factors for recurrence and were younger (median age 53 vs. 55). Only patients with a RS ≥ 31 appeared to benefit from anthracyclines (hazard ratio [HR] 0.32; P = 0.009), while those with RS < 31 did not (HR 1.24; P = 0.484). The benefit of anthracyclines increased linearly with higher RS. Of note, in a subgroup analysis of patients with RS ≥ 31, the additional benefit of anthracyclines was limited to patients with tumors > 2 cm
This observation is consistent with that from the FLEX registry, where only patients with a MammaPrint high 2 (−1.000 to −0.570) seemed to benefit from the use of anthracycline (3-year recurrence-free survival [RFS]: +11.3% at high 2 vs. −1.8% at high 1; OʼShaughnessy et al. ASCO 2024; abstr. #511).
Kuemmel et al. (GS3–04): WSG-ADAPT—weekly nab–paclitaxel vs. biweekly paclitaxel [2]
A subprotocol of the ADAPT HR+/HER2– chemotherapy study by the West German Study Group (WSG) compared weekly nanoparticle albumin-bound (nab)–paclitaxel (125 mg/m2 for 8 doses) to biweekly paclitaxel (175 mg/m2 for 4 doses), followed by four cycles of dose-dense EC (epirubicin/cyclophosphamide) in patients with high-risk HR+/HER2– early breast cancer. In the neoadjuvant cohort, the nab–paclitaxel arm showed a higher pathologic complete response (pCR) rate (20.8% vs. 12.9%), but this did not translate into a statistically significant difference in disease-free survival (DFS). Therapy discontinuation rates were similar (7.9% vs. 7.8%), though nab–paclitaxel had slightly more hematologic side effects. Overall neuropathy rates were higher in the paclitaxel arm (23.2% vs. 20.8%), but grade 3 neuropathies were more frequent with nab–paclitaxel (6.9% vs. 3.6%). Thus, weekly nab–paclitaxel does not replace the dose-dense paclitaxel regimen as standard, but offers an alternative for HR+/HER2-patients.
Louis et al. (RF1–03): TRAIN-3—shortened neoadjuvant therapy in radiological complete response [3]
The Dutch phase II TRAIN-3 study investigated shortening neoadjuvant chemotherapy from 9 to 6 or even 3 cycles in patients with HER2-positive stage II or III breast cancer (both HR+ and HR−), who achieved a radiological complete response (rCR) at the interim staging. rCR was defined based on breast magnetic resonance imaging (MRI), axillary ultrasound and a vacuum-assisted core biopsy of the tumor bed in HR+/HER2+ breast cancer. Patients with initially positive axillary lymph nodes also required an ultrasound-guided fine needle aspiration or core biopsy of the lymph node marked at baseline. Neoadjuvant therapy with paclitaxel, carboplatin, trastuzumab, and pertuzumab was administered for up to 9 cycles. If rCR was achieved, therapy duration was reduced. This approach was safe, with 3‑year event-free survival (EFS) rates of 96% in the HR− subgroup and 97% in the HR+ subgroup. However, the phase II design and complex rCR definition limit its immediate clinical application.
Table 1
Increasing benefit of an anthracycline with increasing Oncotype DX Recurrence Score
RS | Adj-HR, DRFI |
|---|---|
15 | 1.00 (0.51–1.95) |
20 | 0.96 (0.53–1.75) |
25 | 0.89 (0.49–1.61) |
30 | 0.79 (0.45–1.39) |
35 | 0.69 (0.40–1.18) |
40 | 0.60 (0.34–1.05) |
45 | 0.52 (0.27–0.98) |
50 | 0.45 (0.21–0.96) |
Immunotherapy
Geyer et al. (GS3-05): NSABP b-59/GeparDouze—atezolizumab +chemotherapy in early TNBC [4]
The NSABP B‑59/GeparDouze study, a US–German collaboration, was a multicenter, double-blind, randomized, placebo-controlled phase III trial for patients with early TNBC with tumors > 2 cm or positive lymph nodes. A total of 1550 patients received neoadjuvant chemotherapy plus either placebo or the anti-PD-L1 antibody atezolizumab, followed by postoperative continuation of atezolizumab or placebo for a total of one year. Postoperative capecitabine was allowed for patients without pCR. Although atezolizumab increased pCR rates from 57.0 to 63.3%, the primary endpoint EFS, was not significantly different after a median follow-up of 49 months (HR 0.80; 95% confidence interval [CI] 0.62–1.03; P = 0.08). As expected, atezolizumab was associated with immune-related side effects.
The lack of EFS improvement contrasts with the KEYNOTE-522 study, which showed benefits from the addition of the anti-PD‑1 antibody pembrolizumab (Schmid P et al. N Engl J Med 2024; PMID: 39282906). Possible explanations include a lower-risk population and better chemotherapy regimens in the NSABP B‑59 study (dose-dense, adjuvant capecitabine allowed), and differences between anti-PD-L1 and anti-PD‑1 antibodies. Notably, a large biomarker analysis in KEYNOTE-522 presented at the SABCS 2024 meeting failed to identify predictive biomarkers for pembrolizumab efficacy (O’Shaughnessy et al. SABCS 2024; LB1–07).
Shao et al. (GS3-06): CamRelief—camrelizumab +chemotherapy in early TNBC [5]
The CamRelief study evaluated the efficacy of the Chinese anti-PD‑1 antibody camrelizumab in early or locally advanced TNBC. In this randomized, double-blind, phase III trial involving 441 patients, camrelizumab combined with chemotherapy significantly improved the pathological complete response (pCR) rate compared to placebo (56.8% vs. 44.7%; P = 0.0038). However, similarly to the NSABP B‑59 study, there was no statistically significant difference in EFS (HR 0.80; 95%CI 0.46–1.42; P = 0.224) or distant disease-free survival (DDFS; HR 0.62; 95%CI 0.29–1.33; P = 0.107) between the two groups.
Side effect management
Karsten et al. (GS1–06): PRO-B—patient-reported outcomes via app and alert system [6]
The multicenter, randomized PRO‑B study examined whether weekly collection of patient-reported outcomes (PROs) via an app, linked to an alert system for the treating breast center, affected fatigue and survival in patients with metastatic breast cancer undergoing active antitumor therapy. The control group reported symptoms every 3 months without alerts. After 6 months, patients in the experimental arm experienced significantly less fatigue. Additionally, 12-month overall survival was significantly improved (87.6% vs. 84.7%; HR 0.71; 95%CI 0.51–0.99; P = 0.043). In the TNBC subgroup, a similar trend was observed, though not statistically significant.
Peppone et al. (RF2–06): olanzapine vs. prochlorperazine for refractory nausea [7]
A large double-blind, placebo-controlled phase III study in the USA compared olanzapine and prochlorperazine for refractory chemotherapy-induced nausea. Among 1363 patients, those experiencing significant nausea despite standard prophylaxis after cycle one were randomized to receive olanzapine, prochlorperazine, or placebo during the second chemotherapy cycle. Both medications significantly reduced nausea compared to placebo, but olanzapine was more effective in controlling severe nausea and improving quality of life.
Take-home messages
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Chemotherapy optimization: In TAILORx, only patients with an Oncotype DX Recurrence Score ≥ 31 benefited from adjuvant anthracycline-containing chemotherapy. In WSG-ADAPT, weekly nab–paclitaxel showed higher pathological complete response (pCR) rates than biweekly paclitaxel, but without significant DFS improvement. TRAIN‑3 demonstrated that shortened neoadjuvant chemoimmunotherapy (3 or 6 cycles) was as effective as 9 cycles in HER2-positive breast cancer, provided a strict radiological complete response was achieved.
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Immunotherapy in early TNBC: Atezolizumab and camrelizumab increased pCR rates when combined with chemotherapy, but did not significantly impact event-free survival.
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Side effect management: Olanzapine proved superior to prochlorperazine in treating refractory chemotherapy-induced nausea. Collecting patient-reported outcomes (PROs) via apps with alert systems not only improved quality of life but also enhanced survival in patients with metastatic breast cancer.
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Conflict of interest
S.P. Gampenrieder received honoraria from Roche, Daiichi Sankyo, Seagen, Novartis, BMS, AstraZeneca, Pfizer, Janssen, Gilead, Eli Lilly and MSDM; travel support from Roche, Amgen, Novartis, Pfizer, Bayer, Celgene, Daiichi Sankyo, Janssen and Gilead; and research grants from Roche, Daiichi Sankyo, Novartis, Pfizer, Caris Life Sciences, Lilly, Seagen, Gilead, AstraZeneca and Stemline Therapeutics. V. Castagnaviz received honoraria from Daiichi Sankyo, AstraZeneca, Roche, Novartis, Roche, and travel grants from Eli Lilly, Daiichi Sankyo, Gilead, Pfizer, Seagen, AstraZeneca, Roche, Caris Life Science, Pierre Fabre.
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