Citations 2
Impact of BMI in Patients With Early Hormone Receptor–Positive Breast Cancer Receiving Endocrine Therapy With or Without Palbociclib in the PALLAS Trial
Pfeiler, Georg , Hlauschek, Dominik , Mayer, Erica L. , Deutschmann, Christine , Martín, Miguel , Loibl, Sibylle , Balić, Marija , Park, Haeseong , Prat, Aleix , Bajetta, Emilio, Balko, Justin M. , Bellet-Ezquerra, Merixtell, Bliss, Judith M. , Burstein, Harold J. , Fohler, Hannes, Haddad, Tufia C. , Jassem, Jacek , Lee, Soo Chin , Los, Maartje , Mamounas, Eleftherios P. , Morris, Patrick G. , Gal‐Yam, Einav Nili , Ring, Alistair , Shepherd, Lois E. , Thomssen, Christoph , Machacek‐Link, Jana, Schurmans, Céline , Huang, Xin , Gauthier, Eric , Fesl, Christian , Dueck, Amylou C. , Gnant, Michael , Investigators, on behalf of the PALLAS Groups and, Cameron, David , Steger, Guenther G. , Bellet, Meritxell , Dueck, A. C. , Martin, Miguel , Zdenkowski, Nicholas , Loibl, Sibylle , Balic, Marija , Park, Haeseong , Isaacs, Claudine , Wrangle, John M , Bliss, Judith , Burstein, Harold J , Cardoso, Fatima , Foukakis, Theodoros , Gelmon, Karen A , Goetz, Matthew P , Haddad, Tufia C , Iwata, Hiroji , Jassem, Jacek , Lee, Soo-Chin , Mamounas, Eleftherios P. , Miller, Kathy D , Munzone, Elisabetta , Gal-Yam, Einav Nili , Shepherd, LE , Singer, Christian F , Thomssen, Christoph , Tseng, Ling-Ming , Valagussa, Pinuccia , Winer, Eric , Wolff, Antonio C , Zoppoli, Gabriele M. , Schurmans, Céline , Huang, Xin , Gauthier, Eric , Fesl, Christian , DeMichele, Angela , Gnant, Michael , Mayer, Erica L , Prat, Aleix , Cameron, David , Strobl, Stephanie , Meisel, Jane Lowe , Isaacs, Claudine , Cardoso, Fátima , Gelmon, Karen A. , Goetz, Matthew P. , Linderholm, Barbro Kristina , Miller, Kathy D. , Singer, Christian F. , Winer, Eric P. , Wolff, Antonio C. , DeMichele, Angela , Investigators, on behalf of the PALLAS Groups and, El-Abed, Sarra , Rugo, Hope S. , Traina, Tiffany A , Werutsky, Gustavo , Wolmark, Norman
Journal of Clinical Oncology | August 9, 2023 | Volume: 41 | Issue: 33 | Pages: 5118-5130
PURPOSE BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib. METHODS Patients were categorized at baseline according to WHO BMI categories. Neutropenia rates were assessed with univariable and multivariable logistic regression. Time to early discontinuation of palbociclib was analyzed with Fine and Gray competing risk models. Unstratified Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). 95% CIs were derived. RESULTS Of 5,698 patients included in this analysis, 68 (1.2%) were underweight, 2,082 (36.5%) normal weight, 1,818 (31.9%) overweight, and 1,730 (30.4%) obese at baseline. In the palbociclib arm, higher BMI was associated with a significant decrease in neutropenia (unadjusted odds ratio for 1-unit change, 0.93; 95% CI, 0.91 to 0.94; adjusted for age, race ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group at baseline, 0.93; 95% CI, 0.92 to 0.95). This translated into a significant decrease in treatment discontinuation rate with higher BMI (adjusted hazard ratio [HR] for 10-unit change, 0.75; 95% CI, 0.67 to 0.83). There was no significant improvement in iDFS with the addition of palbociclib to ET in any weight category (normal weight HR, 0.84; 95% CI, 0.63 to 1.12; overweight HR, 1.10; 95% CI, 0.82 to 1.49; and obese HR, 0.95; 95% CI, 0.69 to 1.30) in this analysis early in follow-up (31 months). CONCLUSION This preplanned analysis of the PALLAS trial demonstrates a significant impact of BMI on side effects, dose reductions, early treatment discontinuation, and relative dose intensity. Additional long-term follow-up will further evaluate whether BMI ultimately affects outcome.
Ixabepilone plus capecitabine improves overall survival in symptomatic patients with metastatic breast cancer previously treated with anthracycline and taxane in 2 large phase III studies.
Roché, Henri, Perez, Edith A. , Sparano, J. A., Peck, R., Hortobágyi, G. N., Conte, PierFranco , Xu, Binghe , Jassem, Jacek , Mukhopadhyay, P.
Cancer Research | December 30, 2010 | Volume: 69 | Issue: 2_Supplement | Pages: 6114
Abstract Abstract #6114 Introduction:
 Symptomatic patients (pts) with performance status (KPS) 70-80 with locally advanced or metastatic breast cancer (MBC) have worse prognosis than pts with good performance status and are often excluded from clinical trials. Ixabepilone (ixa), the first in a new class of antineoplastic agents, showed clinical benefit in 2 large clinical trials in combination with capecitabine (C) in MBC pts with tumors resistant to (study 046; JCO; 2007) or pretreated with anthracycline (A) and taxane (T) (study 048). In 048, ixa + C, compared to C alone, showed significant increases in PFS (HR 0.79 [0.69-0.90] and ORR (43% vs 29%). A trend toward increased OS was seen in 048 (HR 0.90 [0.78-1.03]) and 046 (HR 0.90 [0.77-1.05]) which did not reach statistical significance. In 046 and 048 trials, a survival benefit was seen with ixa + C in a predefined analysis in a subset of symptomatic KPS 70-80 pts (HR: 0.75 [0.58-0.98], 0.76 [0.60-0.96], respectively). We present a predefined pooled analysis of clinical outcomes in symptomatic pts from both studies to better evaluate the treatment effect in this subset.
 Methods:
 1973 pts with MBC previously treated with an A and T were randomized in phase III trials 046 and 048 to receive ixa (40mg/m2 IV over 3h Q3w) + C (1000mg/m2 PO BID x14d Q3w) or C alone (1250mg/m2 PO BID x14d Q3w). 606 pts from the 2 studies were KPS 70-80. Study outcomes included ORR, PFS and OS.
 Results:
 ORR, PFS and OS favored ixa + C in this pt population.
 
 In asymptomatic pts (KPS 90-100), similar improvement was observed in PFS and ORR; no benefit in OS was seen. Incidence of key treatment related grade 3/4 AEs for ixa + C in this subset of pts was similar to the overall population.
 Conclusions:
 In the pooled analysis, ixa + C demonstrates a survival benefit (2.8 mo) for symptomatic pts (KPS 70-80) failing A and T, which was consistently seen in this pt population in the individual studies as well, indicating that symptomatic pts can benefit from management of their disease and achieve overall clinical benefit with ixa combination. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6114.