Tagrisso Plus Chemo Extends Time Without Cancer Growth in NSCLC

At the 2026 European Lung Cancer Congress, researchers reported that combining Tagrisso (osimertinib) with platinum-based chemotherapy improved how long patients with EGFR-mutant advanced non–small cell lung cancer and TP53 mutations lived without their disease worsening, compared with Tagrisso alone. The findings from the TOP trial highlight a potential treatment approach for patients with cancer who have higher-risk disease features.

Main data that support the findings

Patients who received the combination of Tagrisso and chemotherapy experienced a median progression-free survival of 34 months compared with 15.6 months for those who received Tagrisso alone. This means patients in the combination group lived significantly longer without their cancer growing or spreading.

The benefit of the combination treatment was consistent across multiple patient groups, including differences in age, sex, smoking history, EGFR mutation type and whether cancer had spread to the brain or liver.

“These findings provide key evidence to support a molecular risk–guided, individualized treatment strategy for EGFR-mutated advanced NSCLC,” lead study author Dr. Yunpeng Yang said during the presentation. Yang is a member of the Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine in Guangzhou, China.

An early look at overall survival also showed a longer median survival with the combination approach, at 48.4 months compared with 36.5 months for Tagrisso alone.

Tumor response rates were higher with the combination. The overall response rate, which reflects how many patients had tumor shrinkage, was 82.9% with the combination versus 71.6% with Tagrisso alone. Additionally, more patients achieved disease control, defined as tumor shrinkage or stability, with the combination (91.8% versus 84.5%).

The duration of response was also longer with the combination, lasting a median of 32.7 months compared with 15.3 months for patients receiving Tagrisso alone.

Trial details

The TOP trial was a randomized, multicenter study that enrolled patients with previously untreated stage IV or recurrent nonsquamous non–small cell lung cancer with EGFR mutations and concurrent TP53 mutations.

A total of 292 patients were assigned to one of two groups: 146 patients received Tagrisso plus chemotherapy and 148 patients received Tagrisso alone. Chemotherapy included pemetrexed and carboplatin given every three weeks for four cycles, followed by maintenance therapy with Tagrisso and pemetrexed. Treatment continued until disease progression or side effects became too difficult to manage.

Patients enrolled in the study generally had good functional status, and those with stable brain metastases were allowed to participate. The median age in the combination group was 57 years, and most patients were female, had never smoked and had tumors with exon 19 deletion mutations.

At the time of analysis, more patients in the combination group remained on treatment compared with the Tagrisso-alone group.

The study evaluated several outcomes, including progression-free survival as the primary end point, as well as overall survival, response rates, duration of response, safety and patient-reported outcomes.

“The central debate has shifted from establishing the efficacy of combination therapy to another question: Which patient population truly needs treatment intensification?” Yang said.

Safety

Side effects were common in both groups, occurring in 97.9% of patients receiving the combination and 94.6% of those receiving Tagrisso alone. More severe side effects were reported more often with the combination, occurring in 62.4% of patients compared with 14.9% in the monotherapy group.

Serious side effects related to treatment occurred in 10.6% of patients receiving the combination and 1.4% of those receiving Tagrisso alone. One treatment-related death occurred in the combination group and was linked to low platelet counts.

Side effects led to treatment discontinuation in 26.2% of patients in the combination group compared with 1.4% in the Tagrisso-alone group. Dose reductions and interruptions were also more common with the combination.

Common side effects in the combination group included anemia, low white blood cell counts, low platelet counts, fatigue, decreased appetite, diarrhea, rash, nausea and constipation. Laboratory changes, such as increased liver enzymes and electrolyte imbalances, were also reported.

“The safety profile in this study was consistent with that reported in the phase 3 FLAURA2 study, with no new safety signals,” Yang reported.

“The most common [side effects] in the combination group were hematologic toxicities, and the majority of non-hematologic [side effects] were grade 1 (mild) or 2 (moderate). The most common [side effects] in the monotherapy group were lymphocyte count decrease and diarrhea,” Yang concluded.

References

1. “Tagrisso with or without chemotherapy as first-line treatment in EGFR-mutant advanced NSCLC with concurrent TP53 mutations (TOP study)” by Dr. Yunpeng Yang, et al., 2026 European Lung Cancer Congress.

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