Category: 3. Business

Dalpiciclib (SHR6390; Jiangsu Hengrui Medicine Co) in combination with endocrine therapy (ET) significantly improved progression-free survival (PFS) in first- and later-line settings for hormone receptor-positive (HR+)/HER2– advanced breast cancer. These data, from a first interim analysis of the phase 3 DAWNA-A trial (NCT03927456), were presented at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago.¹

Dalpiciclib is an oral CDK4/6 inhibitor that targets overexpressed CDK4/6 proteins to interrupt cancer cell proliferation. It is approved in China by the National Medical Products Administration in combination with fulvestrant (Falsodex; AstraZeneca) for the treatment of relapsed/progressed HR+/HER2- advanced breast cancer. As of 2025, it’s not approved by the FDA.^2,3

DAWNA-A is a randomized, double-blind, phase 3 study evaluating dalpiciclib plus ET as adjuvant therapy in 5274 patients (ages 18 to 75) with stage 2 to 3 HR+/HER2– breast cancer and pathologically confirmed ipsilateral axillary lymph node involvement. They were randomized 1:1 to receive either daily dalpiciclib at a dosage of 125 mg (3 weeks on/1 week off for 2 years) plus ET (letrozole 2.5 mg; anastrozole 1 mg; tamoxifen 10 mg; toremifene 60 mg daily for 5 years; n = 2640) or placebo + ET (n = 2634). The trial’s primary end point was invasive disease-free survival (iDFS), with secondary end points including DFS, distant DFS (DDFS), overall survival (OS), and safety.⁴

Pre- and perimenopausal patients received LHRH agonists, with use in perimenopausal patients determined at the investigator’s discretion. Stratification factors included menopausal status (pre/perimenopausal vs postmenopausal), clinical stage (2 vs 3), number of involved lymph nodes (<4 vs ≥4), and receipt of adjuvant chemotherapy (yes vs no).⁴

At the median follow-up of 20.3 months, patients treated with dalpiciclib in combination with ET achieved superior iDFS compared with the placebo group (HR 0.56, 95% CI 0.43–0.71; 1-sided P < .0001), and these benefits were consistent across subgroups. Additionally, dalpiciclib plus ET was preferred over placebo plus ET by DFS and distant DFS.⁴

“The phase III DAWNA-A met its primary end point at the first internal analysis, with significant iDFS benefits with dalpiciclib plus [ET] versus placebo plus [ET],” said Zhi-Ming Shao, PhD, Fudan University Shanghai Cancer Center, in their presentation.⁴

The safety profile was favorable, with no deaths due to treatment-related adverse events (TRAEs). Treatment-related adverse events (TRAEs) occurred in 3.7% of patients in the dalpiciclib arm and 1.5% in the placebo arm, leading to treatment discontinuation in 2.1% and 0.8% of patients, respectively.⁴

“Our data supports dalpiciclib plus [ET] as a neoadjuvant treatment option for [HR+/HER2–] early breast cancer, especially in Chinese populations,” concluded Shao.⁴

REFERENCES

1. A study of SHR6390 in combination with fulvestrant in patients with HR positive and HER2 negative advanced breast cancer. Updated June 3, 2021. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT03927456

2. New CDK4/6 Inhibitor offers benefits for advanced-stage, hormone receptor-positive, HER2-negative breast cancer. Breastcancer.org. November 16, 2022. Accessed July 11, 2025. https://www.breastcancer.org/research-news/new-cdk46-inhibitor-offers-benefits-for-advanced-stage-hormone-receptor-positive-her2-negative-breast-cancer

3. NMPA approves AiRuiKang® (dalpiciclib) in combination with fulvestrant for the treatment of relapsed/progressed HR+/HER2- advanced breast cancer. Hengrui. January 3, 2021. Accessed July 11, 2025. https://www.hengrui.com/en/media/detail-149.html

4. Shao ZM, Hao J, Wang S, et al. Dalpiciclib (Dalp) plus endocrine therapy (ET) as adjuvant treatment for HR+/HER2– early breast cancer (BC): The randomized, phase 3, DAWNA-A trial. 2025 ASCO Annual Meeting. Chicago, IL. Abstract 515

RIYADH, (UrduPoint / Pakistan Point News / WAM – 11th Jul, 2025) The non-oil trade surplus of Saudi Arabia with the Gulf Cooperation Council (GCC) countries recorded an annual growth rate of 203.2% to more than SAR2 billion in April. It soared to around SAR3,511 million from SAR1,158 million in the same month last year.

According to preliminary data from the International Trade Bulletin for April, published by the General Authority for Statistics (GASTAT), the total volume of non-oil trade, including re-exports, between Saudi Arabia and GCC countries amounted to around SAR18,028 million. This reflects a year-on-year growth of 41.3%, with an increase of SAR5,271 million from SAR12,757 million in April 2024.

Non-oil commodity exports, including re-exports, rose by 55%, totaling SAR10,770 million, up from SAR6,958 million in April of the previous year, an increase of over SAR3,812 million, Saudi Press Agency (SPA) reported citing the GASTAT figures.

Meanwhile, the value of national non-oil commodity exports reached around SAR3,031 million, compared to SAR2,675 million in April 2024, achieving a year-on-year growth rate of 13.

3%, with an increase estimated at SAR356 million.

Additionally, the value of re-exports surged by 81%, reaching SAR7,738 million compared to SAR4,282 million, an increase of SAR3,456 million.

Saudi Arabia’s imports from GCC countries stood at SAR7,258 million in April 2025, compared to SAR5,799 million last year, achieving a year-on-year growth of 25.2%, with an increase of SAR1,459 million.

The data indicated that the United Arab Emirates ranked first in terms of non-oil trade volume with Saudi Arabia, amounting to SAR13,533 million, representing about 75.1% of the total.

Bahrain followed in second place with a trade value of SAR1,798 million (10%), while Oman ranked third with SAR1,454 million (8.1%). Kuwait was fourth with SAR819.9 million (4.5%), and Qatar came next with a value of SAR422.1 million (2.3%).

First-line treatment with dostarlimab-gxly (Jemperli) plus carboplatin and paclitaxel prolonged time to first subsequent therapy (TFST) and time to second subsequent therapy (TSST) vs placebo plus chemotherapy in patients with primary advanced or recurrent endometrial cancer regardless of age, according to findings from a post hoc analysis of part 1 of the phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial (NCT03981796).¹

Results presented during the 2025 ESMO Gynecological Cancers Congress showed that, in the overall patient population (n = 494), the median TFST increased from 10.2 months (95% CI, 9.1-10.9) with the placebo regimen (n = 249) to 15.3 months (95% CI, 12.3-20.1) with the dostarlimab regimen (n = 245; HR, 0.63; 95% CI, 0.51-0.78). The median TSST with the dostarlimab regimen increased to 31.3 months (95% CI, 24.6-40.8) from 19.9 months (95% CI, 16.3-23.1) with the placebo regimen (HR, 0.67; 95% CI, 0.53-0.85).

Among those 70 years of age or older (n = 145), TFST and TSST were prolonged by 8.7 and 8.0 months, respectively, with the dostarlimab (n = 74) vs placebo (n = 71) regimens. For patients younger than 70 years of age (n = 349), the median TFST and TSST were prolonged by 2.9 and 12.6 months, with these respective regimens (n = 171; n = 178).

Comparable results were seen in the mismatch repair–proficient (pMMR)/microsatellite stable (MSS) patient population (n = 376). In this patient population, dostarlimab plus chemotherapy (n = 192) increased the median TFST from 10.2 months (95% CI, 9.0-10.8) with the placebo regimen (n = 184) to 12.7 months (95% CI, 11.4-17.1), translating to a HR of 0.73 (95% CI, 0.58-0.92). The median TSST improved from 18.7 months (95% CI, 15.3-22.0) with the placebo regimen to 26.8 months (95% CI, 22.1-32.6) with the dostarlimab combination (HR, 0.73; 95% CI, 0.57-0.94).

Among those 70 years or older (n = 110), the median TFST and TSST were prolonged by 5.8 and 4.9 months, respectively, with dostarlimab (n = 57) vs placebo (n = 53). Patients younger than 70 years of age (n = 266) saw a 2.3- and 10.8-month increase, respectively, in median TFST and TSST with the dostarlimab (n = 135) and placebo (n = 131) regimens.

“With more than 3 years of follow-up, these results demonstrate the efficacy and tolerability of frontline dostarlimab plus carboplatin and paclitaxel in patients aged 70 years or older…,” Ilana Cass, MD, and colleagues wrote in a poster presentation of the data. Cass is a professor of Obstetrics and Gynecology and chair of the Department of Obstetrics and Gynecology at Geisel School of Medicine, Dartmouth University, in Lebanon, New Hampshire.

Study Background and Design

Previously reported data from RUBY supported the July 2023 FDA approval of dostarlimab in combination with carboplatin and paclitaxel, followed by dostarlimab monotherapy, for adult patients with primary advanced or recurrent endometrial cancer that is dMMR or microsatellite instability high (MSI-H).²

The randomized, double-blind, multicenter study enrolled patients with primary advanced or recurrent endometrial cancer, who were randomly assigned to receive either dostarlimab plus carboplatin and paclitaxel every 3 weeks, followed by dostarlimab monotherapy every 6 weeks for no more than 3 years; or placebo plus carboplatin and paclitaxel, followed by placebo monotherapy.¹ Patients were also categorized as younger than 70 years of age vs 70 years of age or older.

The study’s dual primary end points were progression-free survival (PFS) and overall survival (OS) in the overall population, and PFS in the mismatch repair–deficient/MSI-H patient population. Safety served as a secondary end point, and a subgroup analysis of safety according to age group was performed as a post hoc analysis.

In the current analysis, investigators evaluated TFST, TSST, and safety by age subgroup in the overall and pMMR/MSS patient populations from RUBY. The data cutoff for this post hoc analysis was September 22, 2023, at the time of the second interim analysis.

TFST and TSST were defined as the time from randomization to either the initiation of the first dose of the first or second subsequent anticancer therapy, respectively; or death by any cause.

Additional Subgroup Efficacy and Safety Data

All patients in both treatment arms experienced treatment-emergent adverse effects (TEAEs) regardless of age subgroup, and safety outcomes in both age subgroups were consistent with that of the overall patient population.

Similar increases in safety-related events for both treatment arms were observed in patients aged 70 years or older vs younger than 70 years. The incidence of grade 3 or higher TEAEs in patients aged 70 years or older increased by 5.5% and 8.5% in the dostarlimab and placebo arms, respectively, vs those younger than 70 years. Increases in the rates of serious AEs (+7.5% in the dostarlimab arm; +16.0% the placebo arm), treatment-related immune-related AEs (+4.3%; +4.8%), and TEAEs that led to the discontinuation of dostarlimab or placebo (+6.8%; +0.5%) were also observed.

The rate of immune-related adverse effects (irAEs) related to dostarlimab was higher in the 70 years of age or older subgroup (43.7%) vs the younger than 70 years subgroup (39.4%); the incidence of placebo-related irAEs similarly increased between these respective subgroups (19.7%; 14.9%).

However, death due to TEAEs in the dostarlimab arm was numerically lower in patients 70 years or older (1.4%) vs patients younger than 70 years (2.4%). No deaths due to TEAEs occurred in the placebo arm for either age subgroup.

“Together with the statistically significant PFS and OS benefits and favorable long-term safety profile, these findings support the frontline use of dostarlimab plus carboplatin and paclitaxel as a standard of care in all patients with primary advanced or recurrent endometrial cancer regardless of age,” Cass and coauthors concluded.

Disclosures: Cass had nothing to disclose.

Reference

1. Cass I, Herrstedt J, Jackson A , et al. Time to next treatment by age subgroup in patients with primary advanced or recurrent endometrial cancer (pA/rEC) in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. ESMO Open. 2025;10(suppl 5):105175. doi:10.1016/j.esmoop.2025.107
2. Jemperli (dostarlimab) plus chemotherapy approved in the US as the first new frontline treatment option in decades for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GlaxoSmithKline. July 31, 2023. Accessed July 10, 2025. https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-chemotherapy-approved-in-us-for-new-indication/