ESMO: New standard of care for advanced cervical cancer recommended by researchers

9th November 2023

A short course of induction chemotherapy (IC) ahead of standard treatment with chemotherapy and radiation reduces the rate of relapse and death in women with locally advanced cervical cancer, according to preliminary study findings presented at the European Society for Medical Oncology (ESMO) Congress 2023.

The INTERLACE phase 3 trial enrolled 500 women with squamous, adeno or adenosquamous carcinoma stages IB1/2 to IVA from hospitals in the UK, Mexico, India, Italy, and Brazil over 10 years.

The median patient age was 46 years, overall most women (77%) had stage II cancer, and more than half (57%) were lymph node negative, researchers reported in an abstract simultaneously published in the Annals of Oncology.

Patients were randomised to receive standard chemoradiation (CRT), consisting of external radiation with weekly cisplatin and brachytherapy, or an initial six-week course of IC with carboplatin AUC2 and paclitaxel 80mg/m² followed by standard CRT.

Researchers found women who received IC followed by CRT had five-year progression-free survival rates of 73% compared to 64% in the women who had received CRT alone.

The corresponding five-year overall survival rates were 80% for the IC and CRT group versus 72% for the standard care group.

Given these results, the study authors said IC with CRT should be considered a new standard of care, adding that carboplatin and paclitaxel were cheap, accessible and already approved for patient use.

Lead investigator Dr Mary McCormack, honorary lecturer at UCL Cancer Institute and consultant clinical oncologist at University College London Hospitals, said the trial showed this short course of additional chemotherapy could reduce the risk of the cancer returning or death by 35%.

‘This is the biggest improvement in outcome in this disease in over 20 years,’ she added.

The median overall treatment time for CRT was 45 days in both arms, the researchers reported, with a median interval of seven days between IC and CRT.

They added that 92% of IC patients had five or six cycles of carboplatin and paclitaxel.

Of the IC and CRT group, 84% had four or five cycles of cisplatin while the figure was 89% in the CRT alone group.

Grade ≥3 adverse events were seen in 59% of patients in the IC and CRT group compared with 48% of patients in the CRT alone group.

Commenting on the findings, Professor Ana Oaknin, head of the gynecologic tumors unit at the Vall d´Hebron University Hospital, Barcelona, Spain, called the results encouraging, given the high unmet need for new treatments for advanced cervical cancer.

‘However, it is important to consider the population recruited and the large proportion of patients who had node-negative disease, as we know that positive lymph nodes are indicative of a high risk of relapse,’ she added.

‘Further analysis, in terms of nodal status, would be useful in determining the suitability of the induction chemotherapy approach for different relapse risk groups.’

Professor Oaknin, who was not involved in the research, said ongoing, planned trials might provide information on other ways to improve outcomes beyond CRT alone in high-risk locally advanced cervical cancer.

These included the phase 2 ATOMICC trial investigating anti-PD1 therapy with dostarlimab and the phase 3 e-VOLVE Cervical Study trial assessing the use of the monovalent bispecific human IgG1 monoclonal antibody volrustomig.

Booster COVID-19 vaccination improves immune response in cancer patients undergoing treatment

21st January 2022

A booster COVID-19 dose administered to cancer patients on active treatment leads to an improved immune response in those fully vaccinated

A booster COVID-19 dose to cancer patients with solid tumours in receipt of active treatment, improves their immune response, according to the results of a study by a team from the University Paris Est Créteil, Paris, France.

Since the start of the COVID-19 pandemic, cancer patients have been deemed to be at high risk and thus a priority group for access to available vaccines. Nevertheless, as cancer patients were excluded from the vaccine efficacy trials, the nature and level of the immunogenic response to vaccination among cancer patients was uncertain.

Data from a study among cancer patients on treatment has shown that after a first dose, 29% of patients were seropositive and that this rate increased to 86% after the second dose. But there appears to be only one study in patients with cancer who have received a third dose of vaccine and which appeared to show greater immunogenicity.

For the present study, the French team wanted to evaluate the immunogenicity of two and three doses of a COVID-19 vaccine in cancer patients currently receiving chemotherapy and how this was affected by the type of oncology treatment and the timing of vaccination.

Using a prospective, observational design, the team included patients with solid organ active cancer, which they defined as ‘histologic confirmation of solid cancer under treatment within the previous 6 weeks or starting treatment during the next 2 weeks.’

The researchers collected information on the patient’s cancer diagnosis, therapy and cancer stages. All patients had received two doses of BNT162b2 on days 0 and 21 and those who had a prior history of COVID-19 infection or evidence of antibodies before vaccination were excluded.

A booster COVID-19 (i.e., third) dose was offered to all of those who had a weak humoral response one month after the second dose, which was defined by an anti-spike protein antibody level below 1000 units.

Findings

In total, 163 patients with a median age of 66 years (53% male) were included in the analysis. The most common form of treatment was chemotherapy (75%), followed by targeted therapy (16%) and immunotherapy (9%).

One month after the first vaccine, only 15% of patients had anti-spike antibody titres > 1000, although one month after the second dose, this proportion increased to 65%. A booster COVID-19 dose was offered to 36 patients whose antibody level remained below 1000 units, one month after the second dose. This resulted in 75% of these patients, achieving antibody levels > 1000, one month after their third dose.

In their analysis, age, sex, cancer type, lymphopenia and use of corticosteroids four or more weeks before vaccination, were not associated with the level of immune response at the time of the second dose or even 28 days after the second dose.

However, patients receiving either chemotherapy or targeted therapy had a lower anti-spike level than those given immunotherapy (odds ratio, OR = 5.4, 95% CI 1.5 – 20.2, p = 0.02). Other factors such as the time between vaccination and intravenous chemotherapy administration were also not associated with the intensity of the humoral response.

The authors concluded that a booster COVID-19 dose among those with solid tumours and in receipt of treatment, improved the immune response, highlighting the importance of a third dose in this patient cohort.

Citation

Fenioux C et al. SARS-CoV-2 Antibody Response to 2 or 3 Doses of the BNT162b2 Vaccine in Patients Treated With Anticancer Agents JAMA Oncol 2022.