For several years, the overexpression of the HER2 receptor in breast cancer has been correlated with a poor prognosis and an increased risk of developing brain metastases. Currently, the combination ...of anti-HER2 double blockade and taxane and trastuzumab emtansine (T-DM1) are considered the standard treatments for metastatic breast cancer overexpressing these receptors in the first and second line. Very recently, the development of a new antidrug conjugate, trastuzumab-deruxtecan, has improved the overall survival of patients, even in second-line treatment. However, trastuzumab-deruxtecan has become a new standard. Despite the benefits of these antidrug conjugates, this benefit in patients with brain metastases remains unclear. Tucatinib is a new tyrosine kinase inhibitor that has given hope for the treatment of these patients. The objective of this article was to review data on the established drugs and novel agents for HER2-positive MBC and to discuss how to incorporate anti-HER2 therapies in first and later-line settings.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Additional systemic treatment for early breast cancer in elderly is challenged by increasing comorbidities with age. We aimed to examine the effect of additional chemotherapy on overall ...survival in patients aged 70 years or older and the impact of comorbidities on chemotherapy benefit.
Methods
This retrospective monocentric cohort study includes data from all patients aged 70 years and older who underwent surgery for an early breast cancer from 1997 to 2016. A propensity score analysis allowed adjustment for chemotherapy prescription preferences based on tumour characteristics.
Results
Of 15,599 patients who had surgery for an early breast cancer, 1743 (11.2%) over 70 years old were included, of whom 269 (15.4%) had received additional chemotherapy. Median follow-up was 5.3 years. Multivariate analyses on the propensity-score weighted cohort (
n
= 1 354) identified improved overall survival in patients with chemotherapy
versus
without (HR 0.54, 95% CI 0.31–0.92). Chronic obstructive pulmonary disease (HR, 2.16, 95% CI 1.40–3.34) and polypharmacy (HR 1.40, 95%CI 1.07–1.84) were associated with worse overall survival. No statistically significant interactions were identified between these comorbidities and chemotherapy prescription.
Conclusion
Additional chemotherapy in elderly with early breast cancer is feasible and associated with overall survival benefit, supporting the importance of chemotherapy considerations in this population, and of avoiding undertreatment based on chronological age considerations alone.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate because 75% of patients are diagnosed with advanced stage III-IV disease. About 50% of patients are ...now treated with neoadjuvant chemotherapy followed by interval debulking surgery (IDS). In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent IDS. Across seven studies with more than 12,000 patients, including six large randomized clinical trials and a national cancer registry, along with a mega-analysis database with 5842 patients, the modeled CA-125 ELIMination rate constant K (KELIM), the calculation of which is based on the longitudinal kinetics during the first three cycles of platinum-based chemotherapy, was shown to be a reproducible indicator of tumor intrinsic chemosensitivity. Indeed, KELIM is strongly associated with the likelihood of complete IDS, subsequent platinum-free interval, progression-free survival, and overall survival, along with the efficacy of maintenance treatment with bevacizumab or veliparib. As a consequence, KELIM might be used to guide more subtly the medical and surgical treatments in a first-line setting. Moreover, it could be used to identify the patients with poorly chemosensitive disease, who will be the best candidates for innovative treatments meant to reverse the chemoresistance, such as cell cycle inhibitors or immunotherapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
A major question when treating HR+/HER2− metastatic breast cancer (MBC) is whether early introduction of chemotherapy (CT) increases endocrine resistance. We aimed to describe ...progression-free survival (PFS) under first endocrine therapy (ET) depending on whether given before or after CT in a large nationwide cohort, in the pre-CDK era.
Methods
The real-life retrospective ESME database includes all patients with MBC whose first-line treatment was initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. Our primary objective was to compare PFS from start of first ET in patients with HR+/HER2− MBC who received ET or CT first.
Results
We identified 6293 patients who received at least one ET line during their first two therapeutic lines for MBC. As first-line therapy, 3832 (60.9%) received ET alone (ET1 1st group), whilst 2461 (39.1%) received CT, including 2024 patients (32.2%) with maintenance ET after CT (ET1 after CT group). Median PFS under first ET was 12.4 months (95% CI 11.9–13.1) in ET 1st group vs. 12.6 months in ET1 after CT group (95% CI 12.1–13.4), HR 0.96 (95% CI 0.90–1.01,
P
= 0.1277).
Conclusions
PFS under first ET appears identical whether prescribed before or after chemotherapy. These data suggest chemotherapy does not promote endocrine resistance.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). ...All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0; p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5; p < 0.00043) and shorter OS (HR 4.5; p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: ICIs have dramatically improved patient outcomes in different malignancies. However, the impact of liver metastases (LM) and number of metastatic sites (MS) remains unclear in patients ...treated with single-agent anti-PD(L)1. Methods: We aimed to assess the prognostic impact of LM and MS number on progression-free survival (PFS) and overall survival (OS) in a large single-arm retrospective multicentric cohort (IMMUCARE) of patients treated with anti-PD(L)-1 for different solid tumors. Results: A total of 759 patients were enrolled from January 2012 to October 2018. The primary tumor types were non-small cell lung cancer (71%), melanoma (19%), or urologic cancer (10%). At the time of ICI initiation, 167 patients (22%) had LM and 370 patients (49%) had more than MS. LM was associated with a shorter median PFS of 1.9 months (95% CI: 1.8−2.5) vs. 4.0 months (95% CI: 3.6−5.4) in patients without LM (p < 0.001). The median OS of patients with LM was of 5.2 months (95% CI: 4.0−7.7) compared with 12.8 months (95% CI: 11.2−15.1) (p < 0.001). Interestingly, LM were not associated with shorter PFS, or OS compared to other MS types (brain, bone, or lung) in patients with only one MS. Patients with multiple MS also had poor clinical outcomes compared to patients with only one MS. The presence of LM and MS number were independent prognostic factors on overall survival. Conclusion: The presence of LM or multiple MS were associated with poorer survival outcomes in patients treated with anti-PD(L)-1.
Age-related immune dysfunction might impair the efficacy of immune checkpoint inhibitors (ICIs) in older patients. We aimed to evaluate the impact of age on clinical outcomes and tolerance of ICIs in ...a real-life setting.
All patients receiving a single-agent ICI (cytotoxic T-lymphocyte-associated protein 4 CTLA-4 or programmed death(ligand)1 PD(L)-1 inhibitors) for the standard treatment of a locally advanced or metastatic cancer were included in this retrospective multicentric series. The primary end-point was overall survival (OS). Progression-free survival (PFS) and immune-related adverse events (irAEs) were secondary end-points. The impact of age was assessed using the threshold of 70 years.
A total of 410 patients were included, for 435 lines of treatment, including 150 lines (34%) given to patients aged 70 years or older. The primary tumour types were lung cancer (n = 304, 74%), melanoma (n = 79, 19%) and urologic cancer (n = 27, 7%). Most of the administered treatments were PD(L)-1 inhibitors (n = 356, 82%). Median follow-up reached 46 months in the CTLA-4 cohort, and 20 months in the PD(L)-1 cohort. In both treatment cohorts, age did not impact OS (respectively, HR = 0.82, 95% CI 0.5–1.4; log-rank P = 0.49 and HR = 0.9, 95% CI 0.7–1.1; log-rank P = 0.27) or PFS (HR = 0.7, 95% CI 0.4–1.1; log-rank P = 0.13 and HR = 0.9, 95% CI 0.7–1.1; log-rank P = 0.19). Grade 3–4 irAEs rates were not statistically different between older and younger patients (11% vs 12%, P = 0.87).
In a large real-world series of patients treated by ICI monotherapy, the long-term clinical outcomes were not statistically different between older or younger patients, with no increased immune-related toxicity.
•Long-term outcomes of elderly receiving immune checkpoint inhibitors (ICIs) are similar to those of younger patients.•ICI in older patients is not associated with increased immune-related toxicity.•ICI therapy represents an acceptable option for elderly with advanced cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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