Overall Survival in Patients with Endometrial Cancer Treated with Dostarlimab plus Carboplatin-Paclitaxel in the Randomized ENGOT-EN6/GOG-3031/RUBY Trial.

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer. At the first interim analysis, the trial met one of its dual-primary endpoints with statistically significant progression-free survival benefits in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase 3, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer who were randomly assigned (1:1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual-primary endpoint. RESULTS: A total of 494 patients were randomized (245 in dostarlimab arm; 249 in placebo arm). In the overall population, with 51% maturity, RUBY met the dual-primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death (HR = 0.69; 95% CI, 0.54-0.89; P = 0.0020) in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32; 95% CI, 0.17-0.63; nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair proficient/microsatellite stable (MMRp/MSS) population (HR = 0.79; 95% CI, 0.60-1.04; nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful overall survival benefit in the overall population of patients with primary advanced or recurrent endometrial cancer while demonstrating an acceptable safety profile.

Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study.

PURPOSE: In HER2-positive breast cancer (HER2+ BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC. METHODS: Patients with clinical stage II-III HER2+ BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion. RESULTS: In 30 evaluable patients, the pCR rate was 77% (95% CI 58-90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade ≥ 3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade ≥ 2 diarrhea (40%) than the standard loading dose (60%). CONCLUSION: pCR rates with our regimen were as high as reported with TCHP with fewer grade ≥ 3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+ BC. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT02789657.

Body mass index (BMI), postoperative appearance satisfaction, and sexual function in breast cancer survivorship.

PURPOSE: We sought to explore the correlation between BMI and postoperative sexual function, body image, and breast-specific sensuality before and after breast cancer surgery. METHODS: A cross-sectional survey of patients at least 1 year from surgery employed the Female Sexual Function Index (FSFI) and investigator-generated questions. Patients who underwent lumpectomy (L), mastectomy (M), and mastectomy with reconstruction (MR) were compared across three BMI groups: normal weight, overweight, and obese. RESULTS: Two hundred fifty-five patients underwent lumpectomy (L, n = 174), mastectomy (M, n = 22), or mastectomy with reconstruction (MR, n = 59). Median age was 57 (range 30-93) and median BMI was 28 (range 19-45). Obese and overweight women reported more appearance dissatisfaction (18.1 and 13.0%) than normal weight women (4.1%) (p = 0.01). Lower satisfaction was associated with increasing BMI within the MR group (p = 0.05). The obese group's median FSFI score met criteria for sexual dysfunction (25.90, range 11.30-33.10). More overweight women reported their chest played an important role in intimacy before and after surgery, but a postoperative decline in the importance of this role was observed in all groups. CONCLUSIONS: Greater post-treatment BMI is inversely related to postoperative appearance satisfaction, particularly in those undergoing mastectomy with reconstruction. The role of the breast in intimacy is greatest in overweight women, but decreases postoperatively in all BMI groups. IMPLICATIONS FOR CANCER SURVIVORS: Postoperative appearance satisfaction and sexual function seems to be correlated to post-treatment BMI, which highlights the need to encourage perioperative weight management for improved survivorship outcomes.

The impact of mastectomy type on the Female Sexual Function Index (FSFI), satisfaction with appearance, and the reconstructed breast's role in intimacy.

BACKGROUND: As mastectomy rates increase and overall survival for early breast cancer improves, a better understanding of the long-term consequences of mastectomy is needed. We sought to explore the correlation of specific mastectomy type with the Female Sexual Function Index (FSFI), body image satisfaction, and the reconstructed breast's role in intimacy. METHODS: This study is a secondary analysis of a cross-sectional survey including a retrospective chart review. Patients at least one year from primary surgery were invited to complete the survey between 2012 and 2014. Baseline characteristics and survey responses were compared between three mastectomy groups: total/modified radical (TMRM), skin-sparing (SSM), and nipple-sparing (NSM). All patients underwent reconstruction. RESULTS: Of 453 invited, 268 (59%) completed the survey. Sixty underwent mastectomy with reconstruction: 16 (27%) TMRM, 36 (60%) SSM, and 8 (13%) NSM. There were no significant differences in median total FSFI scores between groups, yet median FSFI scores for the NSM group indicated sexual dysfunction. After adjusting for receipt of chemotherapy and/or radiation, NSM had the lowest median desire score. There was a trend for the NSM group to be the least satisfied with postoperative appearance, but also more likely to report that the chest was "often" caressed during intimacy. However, nearly 40% of the NSM group reported that caress of the reconstructed breast was unpleasant. CONCLUSION: NSM offers patients the greatest opportunity for preservation of their native skin envelope and potentially enhanced cosmetic outcome, but our results did not demonstrate superior sexual function or body image outcomes in this group. By highlighting surgical consequences of mastectomy preoperatively, surgeons may better set realistic patient expectations regarding both aesthetic and functional outcomes after breast cancer surgery. With clearer expectations, patients will have a better opportunity for improved surgical decision-making.