Paclitaxel has been a mainstay of cancer chemotherapy for more than thirty years, and even in an era dominated by targeted agents and immunotherapy, reformulating this well-established drug is quietly reshaping treatment paradigms. A Chinese phase III study of oral paclitaxel solution in gastric cancer, led by Prof. Li Jin, President of Shanghai GOBROAD Cancer Hospital, which is affiliated with China Pharmaceutical University, has now been published. The results show that oral paclitaxel solution is not only non-inferior to the intravenous formulation in median progression-free survival, but significantly extends median overall survival from 6.54 months to 9.13 months (P=0.006), a clear demonstration of superiority in overall survival.
From intravenous infusion to oral administration, and from inpatient treatment to home-based management, the change involves far more than the route of delivery. It reflects a deeper concern for patients' quality of life and for long-term survival benefit. In this interview, Prof. Li Jin looks back at the origins of the study, explains why overall survival improved so markedly, discusses the specific advantages of an oral formulation in the immunotherapy era, and outlines a future in which advanced cancer is managed at home as a chronic disease.
Why Reformulate a Drug That Has Been in Use for Thirty Years?
Our decision to run this study came largely from a pain point we have faced for years in clinical practice: second-line treatment of advanced gastric cancer. The standard second-line options are paclitaxel or docetaxel monotherapy, or a taxane combined with the anti-angiogenic agent ramucirumab. In practice, however, we found that survival was not meaningfully prolonged after intravenous paclitaxel plus ramucirumab. Intravenous administration also places a considerable burden on patients. Patients who reach second-line treatment are generally in poor physical condition, and travelling repeatedly to hospital, queueing and sitting through an intravenous infusion is an extremely unfriendly experience.
We therefore began to ask whether a better formulation, one that makes treatment safer, more effective and more convenient, could improve patients' willingness to continue treatment. That was the core motivation for this clinical study.
This is not the development of a new molecular entity. It is a formulation improvement built on existing intravenous paclitaxel: changing the route from intravenous infusion to oral administration so that treatment is easier to receive. On the basis of the good safety and efficacy data observed in earlier trials, we believed this improvement could bring patients real benefit. The study has now been completed, oral paclitaxel solution has been approved for marketing by China's National Medical Products Administration, and the results have been published in an international academic journal, clear recognition of both the study's international standing and its practical value for patients.
An Unexpected Result: Overall Survival Extended from 6.54 to 9.13 Months
Before this study began, the Korean DREAM study had already shown that oral paclitaxel solution was non-inferior to intravenous paclitaxel for both progression-free survival (2.96 versus 2.63 months) and overall survival (9.74 versus 8.85 months). When we designed our trial, our expectation was therefore to confirm non-inferiority and to offer clinicians a convenient alternative that would allow patients to be treated at home instead of travelling to hospital repeatedly.
As the study progressed and the final data were read out, we had an unexpectedly large surprise: the oral solution not only met non-inferiority in median progression-free survival (3.02 versus 2.89 months, p=0.311), but extended median overall survival from 6.54 months to 9.13 months (P=0.006).
This result means that the study delivered not only convenience but also superior efficacy. It was a highly successful trial, and it reflects the quality of clinical research in China: compared with the Korean DREAM study, our trial used more standardised eligibility criteria, produced cleaner data and was of higher quality overall, which allowed the true advantage of the drug to emerge.
We went on to analyse in depth why an oral drug could produce such a significant overall survival gain. We found that, among patients whose second-line treatment had failed, more patients in the oral group went on to receive third-line treatment, and they stayed on third-line treatment for longer. This suggests that oral paclitaxel solution better preserves patients' performance status, enabling them to tolerate subsequent lines of therapy.
From a pharmacological perspective, oral and intravenous paclitaxel share an identical molecular structure, and with similar plasma exposure progression-free and overall survival should in theory be similar. The difference in overall survival is therefore unlikely to arise from the intrinsic efficacy of the drug. The most likely explanation is that the oral formulation better maintains patients' physical condition, allowing them to receive subsequent treatment in better shape and ultimately extending overall survival. In short, patients lived better, and because they lived better, they lived longer.
In the Immunotherapy Era: No Steroid Premedication, and a Treatment Patients Can Pause
Immunotherapy combined with chemotherapy is now the mainstream first-line approach in advanced gastric cancer. There is an international consensus that steroid use should be minimised during immunotherapy so as not to compromise its efficacy. When choosing a chemotherapy backbone in the second line, clinicians must therefore pay close attention to its effect on the immune microenvironment.
Conventional taxanes require routine steroid premedication, and steroids themselves are immunosuppressive. This inevitably interferes with the patient's immune microenvironment and may even weaken the efficacy of subsequent immunotherapy. One of the greatest advantages of oral paclitaxel solution is that it requires no steroid premedication, and therefore does not affect the patient's immune environment.
There is also a fundamental difference in dosing flexibility. Intravenous paclitaxel is given as a single infusion, and once the drug has entered the body it cannot be withdrawn. With oral paclitaxel, if adverse reactions or excessive toxicity occur during treatment, the patient can pause treatment at any time and avoid a marked decline in performance status.
Some clinicians are already exploring optimised dosing schedules on their own initiative, for example one dose in the morning and one in the evening, in order to prolong plasma exposure and increase the area under the concentration-time curve (AUC), which may improve efficacy. Because each dose is lower, this repeated low-dose approach is better tolerated and may also be more effective. These explorations are valuable for further research. Once investigator-initiated trials have accumulated to a sufficient scale, big-data and real-world analyses may identify schedules better than those available today, at which point formal registration trials can test the refined schedule against the standards of evidence-based medicine.
From Hospital Treatment to Home Management
I believe this model of home management is entirely achievable. In China, second-line treatment of advanced gastric cancer includes, besides taxanes, regimens combined with ramucirumab. Earlier work led by Prof. Xu Ruihua of Sun Yat-sen University Cancer Center on paclitaxel plus fruquintinib showed numerical prolongation of both progression-free and overall survival, although overall survival did not reach statistical significance. Taking into account the efficacy, cost and accessibility of fruquintinib, the CSCO guidelines have included it as a recommendation.
Extending this logic, could we achieve a fully oral home regimen of oral paclitaxel plus oral fruquintinib? This is a direction worth exploring. A dedicated study would be needed to test whether the combination can push median overall survival beyond the 9.13 months already achieved with oral paclitaxel monotherapy, towards 10 to 12 months. If it can, that would confirm the reliability of a fully oral approach and genuinely deliver the goal of home-based management.
With a fully oral regimen, patients would not need to travel to a large specialist hospital. They could complete basic tests in their community, transmit the results remotely to their physician, and in future even have medicines delivered to their home through internet-based medical services. Given the favourable safety profile of oral paclitaxel combined with an oral anti-angiogenic targeted agent, I believe this goal is achievable.
Consultation and Clinical Focus
Prof. Li Jin holds outpatient clinics at Shanghai GOBROAD Cancer Hospital every Monday (all day), Wednesday morning and Saturday morning. His clinical practice focuses on gastrointestinal tumours, with particular expertise in molecular targeted therapy and immunotherapy for gastrointestinal malignancies, clinical research on novel anticancer drugs, and multidisciplinary discussion of complex solid tumours.
Shanghai GOBROAD Cancer Hospital, affiliated with China Pharmaceutical University, is a tertiary medical insurance designated institution located at 170 Taibei East Road, Pudong New Area, Shanghai. The hospital specialises in solid tumours, brings together renowned Chinese and international expert teams, and is built around clinical research and public-benefit services.
This article is a press summary based on the interview with Prof. Li Jin published by Shanghai GOBROAD Cancer Hospital and on the publicly reported results of the Chinese phase III study of oral paclitaxel solution. It is intended for general informational purposes only and does not constitute medical advice, diagnosis, or treatment. Please consult a qualified physician for any medical decision.