According to a recent study, combination therapy with nivolumab plus gemcitabine-cisplatin yielded significantly better outcomes in patients with previously untreated advanced urothelial carcinoma when compared to gemcitabine-cisplatin alone. This study’s findings were published in The New England Journal of Medicine.

This phase 3, multinational, open-label trial included 608 patients with previously untreated unresectable or metastatic urothelial carcinoma. They were randomly assigned to receive either 360mg of intravenous nivolumab plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to 6 cycles, and later on, 480mg nivolumab every 4 weeks for a maximum of 2 years or gemcitabine-cisplatin alone every 3 weeks for up to 6 cycles. The primary outcomes of the study were overall and progression-free survival.

At the median follow-up of 33.6 months, it was observed that with nivolumab-combination therapy (21.7 months), overall survival was longer than with gemcitabine-cisplatin alone (18.9). Similarly, progression-free survival was also longer with nivolumab-combination therapy at 7.9 months compared to 7.6 months with gemcitabine-cisplatin alone (hazard ratio for progression or death,0.72; 95% Cl, 0.59 to 0.88; P = 0.001). At the end of one year, the progression-free survival was 34.2% for nivolumab-combination therapy and 21.8% for gemcitabine-cisplatin alone.

From the above findings, it can be concluded that combination therapy with nivolumab plus gemcitabine-cisplatin may result in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma.

A recent study suggests that neoadjuvant chemotherapy (NACT) along with TPF (docetaxel, cisplatin, and 5FU) shows higher survival benefit over TP (docetaxel and cisplatin) in treating borderline resectable oral cancers. The study findings were published in the European Journal of Cancer.

This phase 3, randomized, superiority study included 495 adult patients with borderline resectable locally advanced oral cancers. These participants were randomized in a 1:1 ratio to receive either TP (N=248) or TPF (N=247). The primary endpoint of the study was overall survival (OS) while the secondary endpoints were adverse events and progression-free survival (PFS).

At the end of 5 years, the OS in TP and TPF arms were 18.5% and 23.9%, respectively. Post NACT, 43.8% of the patients were deemed resectable, but only 34.5% underwent surgery. The 5-year OS was found to be 50.7% in the surgically resected cohort while it was 5% in the unresected cohort following NACT. Adverse events of Grade 3 or above were seen in 97 patients in the TP arm and 179 patients in the TPF arm.

Based on the above results, it can be concluded that NACT with TPF may show greater survival benefit over TP in case of patients with borderline resectable oral cancers and those who can undergo surgery may achieve a relatively good and sustained survival.

Transarterial Chemoembolization (TACE) combined with Lenvatinib (LEN) improves clinical outcomes and is a promising first-line treatment for advanced hepatocellular carcinoma (HCC). This study was published in the Journal of Clinical Oncology.

A multicenter, randomized phase III trial compared 170 advanced HCC patients receiving LEN plus on-demand TACE (LEN-TACE) and 168 advanced HCC patients receiving just LEN monotherapy. LEN was given within 3 days after random assignment and TACE was given one day after the LEN initiation. The primary end point was the overall survival (OS).

After a median follow-up of 17.0 months, the median OS was longer in the LEN-TACE group (17.8 months) than in the LEN monotherapy group (11.5 months) (hazard ratio, 0.45; p < .001). The median progression-free survival in the LEN-TACE group was 10.6 months, whereas in the LEN monotherapy group, it was 6.4 months (hazard ratio, 0.43; p < .001)

This study showed that a combination of TACE and LEN improves clinical outcomes and is a potential first-line treatment for advanced HCC patients.

A recent study showed that the combination of osimertinib with platinum-pemetrexed exhibited improved central nervous system (CNS) efficacy when compared to osimertinib monotherapy. This study’s findings were published in the Journal of clinical oncology. 

In the phase 3 FLAURA2 trial, patients were assigned randomly to receive either osimertinib with platinum-pemetrexed (n= 279) or osimertinib monotherapy (n=278) until disease progression or discontinuation. Brain scans were conducted for all patients at the baseline and upon progression, as well as at scheduled evaluations until progression for those with baseline CNS metastases. The scans were evaluated by a neuroradiologist through a CNS blinded independent central review (BICR).

Based on the baseline CNS BICR, a total of 118 out of 279 patients in the combination group and 104 out of 278 patients in the monotherapy group were included in the CNS full analysis set (cFAS) due to having ≥ one measurable and/or nonmeasurable CNS lesion. Among them, 40 patients from the combination group and 38 patients from the monotherapy group had ≥ one measurable target CNS lesion and were part of the post hoc CNS evaluable-for-response set (cEFR). The hazard ratio (HR) for CNS progression or death was 0.58 in the cFAS , while it was 0.67 for patients who did not have CNS metastases at baseline. The CNS objective response rates in the cFAS were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78), with 59% versus 43% achieving CNS complete response (CR). In the cEFR, CNS ORRs were 88% (73 to 96) versus 87% (72 to 96), with 48% versus 16% achieving CNS CR.

Thus, it can be concluded that the combination of osimertinib and platinum-pemetrexed demonstrated enhanced CNS efficacy compared to osimertinib alone. Additionally, this combination therapy may delay CNS progression, regardless of the baseline CNS metastasis status. These findings strongly support the use of this treatment as a new first-line approach for patients diagnosed with EGFR-mutated advanced non-small cell lung cancer (NSCLC), including those with CNS metastases.