Journal of Clinical Oncology最新文献

Purpose: Guidelines recommend cardiovascular (CV) risk assessment and counseling for cancer survivors. This study evaluated the automated heart-health assessment (AH-HA) clinical decision support tool to promote provider-patient CV health (CVH) discussions in outpatient oncology.

Methods: The AH-HA trial (WF-1804CD), coordinated by the Wake Forest National Cancer Institute Community Oncology Research Program Research Base, randomized practices to the AH-HA tool or usual care (UC) and enrolled survivors receiving routine care ≥6 months after curative cancer treatment. The tool displayed American Heart Association Life's Simple 7 CVH factors (BMI, physical activity, diet, smoking status, blood pressure, cholesterol, and glucose), populated from the electronic health record (EHR), alongside cancer treatments received with cardiotoxic potential. The primary end point was survivor-reported discussion of nonideal or missing CVH factors. A mixed-effects logistic regression model assessed the effect of AH-HA on CVH discussions, adjusting for practice.

Results: Five UC and four AH-HA practices enrolled 645 survivors (82% breast, 8% endometrial, 5% colorectal, and 5% lymphoma, prostate, or multiple types) from October 1, 2020, to February 28, 2023. Most survivors were female (96%; 84% White/non-Hispanic, 8% Black; 3% Hispanic). Nearly all survivors (98%) in AH-HA practices reported a discussion for ≥1 nonideal or missing CVH factor compared with 55% in UC (P < .001). The average number of survivor-reported factors discussed was higher in AH-HA compared with UC (mean, 4.06 v 1.27; P < .001), as were EHR-documented discussions (3.83 v 0.77; P = .03). Survivors in AH-HA practices were also significantly more likely to report a recommendation to see a primary care provider (39%) compared with UC practices (25%, P = .02). Reported recommendations to see a cardiologist were low (approximately 6%) and did not differ between groups.

Conclusion: The AH-HA tool was effective at promoting CVH discussions during routine follow-up care for survivors and recommendations to consult primary care.

Purpose: To investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to secondary cytoreductive surgery (SCS) without neoadjuvant chemotherapy has a benefit on progression-free survival (PFS), as opposed to SCS alone in patients with platinum-sensitive recurrent epithelial ovarian cancer (platinum-free interval, >6 months).

Methods: This was a multicenter randomized phase III study. Random assignment was performed at the time of surgery in cases with residual tumor ≤0.25 cm. HIPEC with cisplatin (CDDP) 75 mg/m² for 60 minutes at 41.5°C was administered at the end of surgery in the experimental arm. Both groups received postoperative platinum-based chemotherapy. The primary end point was PFS. The safety profile and postrecurrence survival (PRS) were the secondary end points.

Results: A total of 167 patients underwent random assignment, 82 patients to SCS plus HIPEC (experimental arm) and 85 to SCS alone (control arm). The median follow-up was 83 months (IQR, 64-102). The median PFS was 23 months (95% CI, 17 to 29) in the group that underwent surgery alone and 25 months (95% CI, 18 to 32) in the group that underwent cytoreductive surgery with HIPEC. The probability of PRS at 5 years was 61.6% (95% CI, 50.8 to 72.4) in the SCS group and 75.9% (95% CI, 66.5 to 85.3) in the SCS plus HIPEC group. The incidence of postoperative adverse events of any grade was similar between the two groups.

Conclusion: The addition of HIPEC to complete or nearly complete primary SCS did not confer a benefit in terms of PFS in patients with platinum-sensitive peritoneal recurrence.

Purpose: Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial.

Methods: Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory.

Results: After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, BRAF-mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% v 61%) and any-grade TRAEs leading to discontinuation (17% v 41%).

Conclusion: Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.

Strategies to bring clinical trials closer to patients gained momentum during the COVID-19 pandemic, enabling more participants to receive treatment and/or testing in their local communities. Incorporation of decentralized trial elements presents both opportunities and challenges, spanning regulatory, technical, and operational aspects. This ASCO research statement includes timely consensus-driven recommendations and a call for engagement of all research stakeholders. ASCO held multistakeholder meetings with leaders in oncology research and concluded that research-related regulatory and administrative requirements and burdens present critical barriers to decentralizing trials. One example is sponsor and contract research organization (CRO) use of US Food and Drug Administration (FDA)'s Statement of Investigator (Form 1572), which was found to exceed FDA's stated intent and used in conservative ways disproportionate to potential risks to participants and scientific integrity. As a result, research sites experience an avalanche of downstream administrative and regulatory activities that consume considerable resources. This statement recommends four key solutions to address such barriers and recalibrate regulatory and administrative expectations for decentralizing trials: (1) FDA should engage the research community in a public-private partnership to modernize standards and enable local access to trials; (2) sponsors and CROs should develop standards and protocols that accommodate flexible approaches, enable local participation, provide clarity around roles and requirements, and promote consistency; (3) research centers, networks, and sites should update policies and procedures to implement decentralized trial elements; and (4) research community should develop a streamlined, uniform mechanism to simplify regulatory data collection and documentation and use it consistently across trials. We can and must prioritize a concerted commitment to simplify and streamline regulatory requirements and practices to broaden access to and participation in cancer clinical trials.

Purpose: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME.

Methods: This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS).

Results: Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group).

Conclusion: This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.

Purpose: To investigate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of inavolisib, a potent and selective small-molecule inhibitor of p110α that promotes the degradation of mutated p110α, in combination with palbociclib and endocrine therapy (ET), in a phase I/Ib study in patients with PIK3CA-mutated, hormone receptor-positive/human epidermal growth factor receptor 2-negative locally advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT03006172).

Methods: Women ≥18 years of age received inavolisib, palbociclib, and letrozole (Inavo + Palbo + Letro arm) or fulvestrant (Inavo + Palbo + Fulv arm) until unacceptable toxicity or disease progression. The primary objective was to evaluate safety or tolerability.

Results: Fifty-three patients were included, 33 in the Inavo + Palbo + Letro arm and 20 in the Inavo + Palbo + Fulv arm. Median duration of inavolisib treatment was 15.7 and 20.8 months (cutoff: March 27, 2023), respectively. Treatment-related adverse events (TRAEs) occurred in all patients; the most frequent were stomatitis, hyperglycemia, and diarrhea; grade ≥3 any TRAE rates were 87.9% and 85.0%; 6.1% and 10.0% discontinued any treatment due to TRAEs in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. No PK drug-drug interactions (DDIs) were observed among the study treatments when administered. Confirmed objective response rates were 52.0% and 40.0% in patients with measurable disease, and median progression-free survival was 23.3 and 35.0 months in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. Available paired pre- and on-treatment tumor tissue and circulating tumor DNA analyses confirmed the effects of study treatment on pharmacodynamic and pathophysiologic biomarkers of response.

Conclusion: Inavolisib plus palbociclib and ET demonstrated a manageable safety profile, lack of DDIs, and promising preliminary antitumor activity.