ASCO Annual Meeting, Chicago, Illinois, US, 31 May-4 June 2024

Risk reduction from HPV vaccination goes beyond cervical cancer

Results from a new study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting suggest that the human papillomavirus (HPV) vaccine is effective in preventing the development of several types of cancers caused by HPV, most particularly head and neck cancer in males.

This study examined the HPV-vaccinated persons’ risk of developing cancers of the head and neck, anal areas, penis, vulva, vagina, and cervix. It also examined the HPV vaccine’s impact on need for surgical treatment of cancer and pre-cancerous lesions.

This study included 1,706,539 patients vaccinated for HPV and 1,706,538 age-matched control patients with no prior HPV-vaccination. A total of 56 per cent were female.

Males vaccinated for HPV had a lower risk of developing all HPV-related cancers (3.4 cases per 100,000 vaccinated patients vs 7.5 per 100,000 unvaccinated patients), as well as a lower risk of developing head and neck cancers compared to unvaccinated males (2.8 cases per 100,000 vaccinated patients vs 6.3 per 100,000 unvaccinated patients).

Females vaccinated for HPV had a lower risk of developing cervical cancer (7.4 cases per 100,000 vaccinated patients vs 10.4 per 100,000 unvaccinated patients) and a lower risk of developing all HPV-related cancers compared to unvaccinated females (11.5 cases per 100,000 vaccinated patients vs 15.8 per 100,000 unvaccinated patients).

However, the odds of developing head and neck cancers, and vulvar or vaginal cancer, were not significantly different in vaccinated females compared to those who had not received the vaccine.

Vaccinated females without a prior diagnosis of abnormal findings during a Pap test were less likely to develop precancerous dysplasia of the cervix and undergo invasive procedures to treat and prevent precancerous lesions.

Chemotherapy before and after surgery benefits some oesophageal cancer patients

For patients with locally advanced oesophageal adenocarcinoma that can be treated with surgery, chemotherapy treatment before and after surgery improved survival when compared to chemoradiotherapy before surgery. This is according to data from the phase 3 ESOPEC clinical trial, which was presented at the 2024 ASCO Annual Meeting.

The trial compared two treatment strategies for locally advanced oesophageal adenocarcinoma that could be treated with surgery. A total of 221 participants were randomised to the FLOT protocol (treatment with chemotherapy before and after surgery) arm and 217 participants were randomised to the CROSS protocol (treatment with chemoradiotherapy before surgery) arm. The majority (89 per cent) of the participants were men, who are more commonly affected by this cancer.

For all study participants, 403 started some form of treatment and 371 went on to receive surgery (191 in the FLOT arm and 180 in the CROSS arm).

In the 90 days after surgery, 4.3 per cent of the participants had died (3.2 per cent in the FLOT arm and 5.6 per cent in the CROSS arm), and after a median follow-up of 55 months, 218 participants had died (97 in the FLOT arm and 121 in the CROSS arm).

Median overall survival was 66 months (five years, six months) in the FLOT arm and 37 months (three years, one month) in the CROSS arm.

At three years, participants who received FLOT had a 30 per cent lower risk of dying than those who received CROSS. The three-year overall survival rates were 57 per cent for the FLOT arm and 51 per cent in the CROSS arm.

Of the 359 participants whose tumour regression status was known, a pathological complete response was achieved in 35 patients in the FLOT arm and 24 in the CROSS arm.

Researchers will now study whether surgery can be avoided in patients with cancers that have a complete pathological response to treatment with the FLOT or CROSS protocols and show no growth during active surveillance.

Antibody-drug conjugate shows good results in multiple myeloma

According to a new study presented at the 2024 ASCO Annual Meeting, adding the antibody-drug conjugate belantamab mafodotin to pomalidomide and dexamethasone for the treatment of relapsed or refractory multiple myeloma was more effective at slowing disease progression or death compared to current standard of care bortezomib plus pomalidomide and dexamethasone.

The recent DREAMM-7 clinical trial showed that a combination of belantamab mafodotin plus bortezomib and dexamethasone slowed the progression of multiple myeloma if the first treatment did not work when compared to daratumumab plus bortezomib and dexamethasone. The DREAMM-8 study combines belantamab mafodotin with pomalidomide and dexamethasone.

In the DREAMM-8 study, people with relapsed and refractory multiple myeloma whose disease had progressed after at least one previous treatment (including lenalidomide) were randomised to receive belantamab mafodotin plus pomalidomide and dexamethasone, or BPd (n=155) or pomalidomide plus bortezomib and dexamethasone, or PVd (n=147). Of all the participants, 60 per cent were men, 86 per cent were white, and the average age was around 67 years.

After a median follow-up of 22 months, the median progression-free survival (PFS) was not reached for the participants who received BPd. For those who received PVd, the PFS was 12.7 months.

At the end of the first year, PFS was 71 per cent for those receiving BPd compared to 51 per cent of those receiving PVd.

The overall response rate was 77 per cent for those receiving BPd compared to 72 per cent for those receiving PVd. Additionally, 40 per cent of patients treated with BPd achieved a complete response or better compared to 16 per cent of patients who were treated with PVd. Among those with disease that responded to treatment, the median duration of response was not yet reached in those who received BPd, and it was 17.5 months in those who received PVd.

“This regimen could become an important treatment option for patients with multiple myeloma at first relapse and for subsequent relapses. It is suitable for a broad range of patients and can be given in a community oncology setting without the need for specialised cancer centre support,” said lead study author Dr Suzanne Trudel, Associate Professor at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada.

Trastuzumab deruxtecan significantly improves PFS in certain breast cancer patients

The antibody-drug conjugate trastuzumab deruxtecan delays cancer growth for women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer that has progressed following endocrine therapy, according to findings from a new phase 3 clinical trial. The data was presented at the 2024 ASCO Annual Meeting.

This study included 866 participants with metastatic breast cancer that was either HER2-low (713 participants) or HER2-ultralow (153 participants). All study participants had received at least one treatment with endocrine therapy, and nearly all participants (90.4 per cent) had also received targeted therapy with a CDK4/6 inhibitor.

The participants were randomly assigned to receive either trastuzumab deruxtecan (436 participants) or a chemotherapy of their doctor’s choice (430 participants, who received either capecitabine, nab-paclitaxel, or paclitaxel).

For those with HER2-low cancer, the PFS was 13.2 months for those who received trastuzumab deruxtecan vs 8.1 months for those who received chemotherapy. Similar results were seen in the small group of patients with HER2-ultralow cancer.

Overall, the patients with HER2-low cancer who received trastuzumab deruxtecan had a 38 per cent lower chance of their cancer growing or spreading compared to those who received chemotherapy.

For those with HER2-low cancer, the objective response rate (ORR) was 56.5 per cent for those who received trastuzumab deruxtecan vs 32.3 per cent for those who received chemotherapy.

For those with HER2-ultralow cancer, the ORR more than doubled for those who received trastuzumab deruxtecan compared with those who received chemotherapy (61.8 vs 26.3 per cent, respectively).

Participants who received trastuzumab deruxtecan were able to receive their treatment for a longer time without experiencing severe side-effects, with a median treatment length of 11 vs 5.6 months for those who received chemotherapy. 

Serious side-effects were more common in the trastuzumab deruxtecan group, with about 41 per cent of participants experiencing a serious side-effect vs about 31 per cent of those who received chemotherapy.

“These results also represent a potential shift in how we classify and treat metastatic breast cancer, as we may have the opportunity to use trastuzumab deruxtecan earlier in the treatment of HR+ metastatic breast cancer and expand trastuzumab deruxtecan into new metastatic breast cancer patients who previously have not been able to benefit from a targeted medicine post-endocrine therapy,” said Dr Giuseppe Curigliano, European Institute of Oncology, Milan, Italy.

The researchers are planning to continue following the patients to assess overall survival outcomes.

Osimertinib poised to change standard of care for some NSCLC cases

Osimertinib improves PFS in patients with unresectable stage III epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) that has been treated with chemoradiotherapy and may be a new standard of care for this population, suggests the results of the international phase 3 LAURA trial presented at the 2024 ASCO Annual Meeting.

“There are currently no approved targeted treatments specifically for unresectable stage III EGFRm NSCLC. With the superior efficacy results along with the robust magnitude of benefit in the LAURA study, osimertinib provides a solution to a large unmet need for this patient population,” said lead study author Dr Suresh S Ramalingam, FASCO, Winship Cancer Institute of Emory University, Atlanta, Georgia, US.

The LAURA trial enrolled people with unresectable stage III NSCLC with EGFR mutations without any disease progression during/after definitive platinum-based chemoradiotherapy. People were randomly assigned on a two-to-one basis to receive osimertinib (143 patients) or a placebo (73 patients).

Osimertinib significantly improved PFS compared with placebo. The median PFS was 39 months in the osimertinib group vs six months with the placebo group.

In the osimertinib group, 74 per cent of participants did not have any cancer growth after 12 months and 65 per cent did not have any cancer growth after 24 months. This is compared with 22 per cent and 13 per cent in the placebo group, respectively.

Osimertinib showed a higher objective response rate when compared with placebo (57 vs 33 per cent, respectively).

The rate of new metastases to the brain was lower in the osimertinib arm (8 per cent) when compared with placebo (29 per cent).

Dual immunotherapy treatment before surgery in melanoma patients

Neoadjuvant immunotherapy given for stage III melanoma, followed by adjuvant therapy only if there is not a deep response to treatment, promises better outcomes for patients than the current standard of care, which is adjuvant immunotherapy alone.

This is according to data from the phase 3 NADINA trial presented at the 2024 ASCO Annual Meeting.

Recent evidence from phase 1 and phase 2 clinical trials has suggested that adding immunotherapy before surgery (neoadjuvant therapy) may help improve patient outcomes.

In the phase 3 NADINA trial, researchers studied whether treatment with ipilimumab and nivolumab before lymph nodes were surgically removed was more effective than treatment with nivolumab after the removal of lymph nodes.

If this treatment did not destroy 90 per cent or more of the tumour cells in the surgically removed lymph nodes (major pathological response), patients would receive adjuvant therapy with nivolumab or, if the tumour contained a mutation in the BRAF gene, they would receive the targeted therapies dabrafenib plus trametinib.

The study included a total of 423 patients; 212 participants receiving neoadjuvant therapy; and 211 participants receiving adjuvant therapy. About two-thirds of the patients were men, and the average age of all participants was about 60 years. The patients were followed for a median of 9.9 months.

The researchers found that there were significantly fewer disease-related events among those who received neoadjuvant therapy than those who received adjuvant therapy (28 vs 72 events, respectively). Those who received neoadjuvant therapy had a 27 per cent absolute reduction in the risk of the disease returning in the first 12 months.

Lymphadenectomy may not be necessary for patients with advanced ovarian cancer

Some patients with advanced epithelial ovarian cancer may not require lymphadenectomy during surgery after chemotherapy, according to research presented at the ASCO 2024 Meeting. The standard approach for this diagnosis is surgery followed by chemotherapy.

Previously, patients would receive lymphadenectomy during their primary surgery; however, surgery without lymphadenectomy became the standard of care following results from the LION clinical trial published in 2019, which showed that omitting lymphadenectomy did not have a negative impact on survival for these patients.

“We already had similar results in patients treated for advanced ovarian cancer with primary surgery followed with adjuvant chemotherapy from the LION trial,” said Lead Author Dr Jean-Marc Classe, Institut de Cancerologie de l’Ouest, Nantes University, Nantes, France. 

“Today, the more frequent strategy in the case of advanced ovarian cancer is interval surgery, which is surgery after neoadjuvant chemotherapy is given. After the publication of the LION trial, the remaining question was: What is the best strategy for considering the removal of the lymph nodes after neoadjuvant chemotherapy? CARACO helps answer this question for some patients.”

The phase III CARACO trial enrolled 379 people with advanced epithelial ovarian cancer whose lymph nodes did not show signs of cancer before or during primary surgery. Between December 2008 and March 2020, participants in the CARACO study were randomly assigned to either undergo a lymphadenectomy or not.

Three-quarters of all participants received chemotherapy prior to surgery, and following the procedure, had no signs of cancer remaining (88 per cent of those who received a lymphadenectomy vs 86 per cent of those who did not).  

After a median follow-up of nine years, researchers found that omitting lymphadenectomy did not impact survival outcomes. Participants who received a lymphadenectomy experienced more serious complications following surgery than those who did not, including needing additional surgery to manage complications from the initial operation, such as bleeding or fluid buildup and needing a transfusion. However, the percentage of participants who died within 60 days of surgery was relatively similar between groups.