Stage 4 Lung Cancer Life Expectancy

Experimental Drugs Could Help Lung Cancer Treatment Research Enter A New Era

More people with non-small cell lung cancer (NSCLC) are likely to benefit from new drugs that target molecular alterations in tumor cells, with less need for chemotherapy, following results of multiple clinical trials reported for the first time in late-breaking presentations at the ESMO Congress 2023.

Better outcomes were achieved with combinations of experimental new drugs targeting common and rare tumor mutations than with standard treatments, with improvements seen in both early and late-stage NSCLC—the type of lung cancer responsible for approximately eight out of 10 cases of the disease.

"The results are very impressive and mean that we can expect major changes in first-line treatment for patients with NSCLC with these targetable tumor cell alterations, and in the way we care for patients whose previous treatment has stopped working," said Professor Alessandra Curioni-Fontecedro, University of Fribourg, Switzerland.

"As a result, it will be more important than ever that lung cancer is diagnosed and treated by lung cancer specialists with access and understanding of molecular testing and findings," she added.

Dr. Elene Mariamidze, Todua Clinic, Tbilisi, Georgia, agreed adding, "We are entering an era of personalized medicine in NSCLC where we are using combinations of novel, targeted agents, and it will be essential to know the whole mutational burden of each patient at diagnosis so we can properly plan the most effective and least toxic approach. The future of lung cancer care lies in finding the right combination of targeted treatment, or chemotherapy with immunotherapy for each patient."

Both Curioni-Fontecedro and Mariamidze highlighted data from studies using a new combination of targeted drugs in patients with advanced or metastatic NSCLC who had an EGFR mutation—one of the most common tumor mutations.

When people were given the combination as first-line treatment, progression-free survival (PFS) was significantly better than with the current most effective treatment for the mutation. In people who had already progressed on this current standard of care, the new targeted drugs, combined with chemotherapy, significantly improved PFS compared with chemotherapy alone.

"We still need to see that the new combination leads to improved overall survival compared with current treatment. We also need to understand more about the effects in patients with brain metastases as it appears that one of the newer EGFR-targeting agents used in these studies has good penetration of brain tissue," said Curioni-Fontecedro.

"These studies show that patients now have a potentially new drug combination for their treatment that works partly by targeting EGFR mutations, and partly by directing immune cells to destroy cancer cells. The fact that the combination worked better than the current standard of care, not just better than placebo, shows tangible benefits for this new approach," added Mariamidze.

Results of NSCLC studies presented at the ESMO Congress 2023 also suggest that using mutation-targeted treatment can reduce the need for chemotherapy in some patients, including those with some rarer tumor alterations for which targeted treatment options have previously been limited. These include patients with operable, early stage ALK-positive NSCLC, those with RET-mutated advanced NSCLC, and those with the less common, more difficult to treat EGFR mutation, Exon 20 insertion, advanced NSCLC.

In addition, study data reinforce the value of adding immunotherapy to chemotherapy in some types of NSCLC, including the use of this treatment before surgery for patients with operable cancers to shrink tumors and indicate likely response to further treatment after surgery (so called, neoadjuvant treatment).

"We know that patients have a better prognosis if pre-surgical treatment of lung cancer leads to tumor disappearance on pathology reports after surgery (pCR-pathologic complete response) than if there are still obvious cancer cells present in post-surgical material. The new results show that adding immunotherapy to chemotherapy before surgery, and then continuing with maintenance immunotherapy for a year after surgery, is more effective than just giving chemotherapy before surgery," Mariamidze pointed out.

Even for patients with advanced or metastatic NSCLC who have relapsed following previous treatments and can only be given chemotherapy, there is good news. Directing chemotherapy more precisely at tumors using antibody drug conjugates, namely antibodies that recognize specific proteins commonly found in lung cancers significantly improved PFS compared to currently used chemotherapy.

"The approach using these antibody drug conjugates will make a big difference for the majority of patients with advanced or metastatic NSCLC who have stopped responding to first and second-line treatments, irrespective of whether they have targetable mutations. We need to know more about the side-effects of this approach but these findings are likely to change the standard of care for these patients," said Curioni-Fontecedro.

Following such promising NSCLC data presented at ESMO 2023, the next step for both Curioni-Fontecedro and Mariamidze is to better understand the sequence of treatments that will give the best outcomes for patients.

"We still face the dilemma of what we do after patients have had these promising new drugs and need further treatment. It will be very important to understand the sequencing of treatment now that we have so many more options for treating NSCLC so that we can achieve the best possible results for each patient," said Curioni-Fontecedro.

"Very few patients benefit from one therapy alone, and most will need combinations of treatments at different times in their lung cancer care. We need further research to show when and how to target different mutations, possibly including new targets, and to help establish the ideal treatment plan for patients with lung cancer who develop extensive disease," concluded Mariamidze.

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Alecensa Reduces Recurrence, Mortality Risk In Lung Cancer Subset

Patients with ALK-positive, early-stage non-small cell lung cancer obtained significant improvement in disease-free survival.

Patients with ALK-positive, early-stage non-small cell lung cancer obtained significant improvement in disease-free survival.

Patients with resected ALK-positive non-small cell lung cancer (NSCLC) experienced a significant improvement in disease-free survival when treated with Alecensa (alectinib), an oral ALK inhibitor, according to recent trial results.

Findings from the phase 3 ALINA trial, which were presented at the 2023 ESMO conference, showed that the targeted therapy elicited superior outcomes than platinum-based chemotherapy across all prespecified subgroups.

Key Findings

The median follow up was 27.9 months with Alecensa and 27.8 months with chemotherapy.

Patients with stage 2 to 3A disease who received Alecensa (116 patients) had a 76% reduced risk of disease recurrence or death compared with those who received platinum-based chemotherapy (115 patients). Among these two groups, the median DFS (the time after treatment ends when a patient with cancer has no signs or symptoms of cancer) was not reached with Alecensa versus 44.4 months with chemotherapy.

Further, the two-year DFS rates were 93.8% versus 63%, respectively. The three-year DFS rates were 88.3% versus 53.3%.

In the intention-to-treat population, which included the entire study population with stage 1B-3A disease, the median DFS was not reached among patients who received Alecensa (130 patients) versus 41.3 months among those who received chemotherapy (127 patients).

Also in the intention-to-treat population, the rates of two-year DFS were 93.6% versus 63.7% and the three-year DFS rates were 88.7% versus 54%, respectively.

Of note, the rate of severe or life-threatening side effects was similar between the two groups: 30% and 31% of patients receiving targeted or chemotherapy, respectively, reported high-grade side effects. No deaths from side effects were reported in either cohort.

"Treatment with adjuvant (Alecensa) resulted in a statistically significant and clinically meaningful improvement in DFS compared with chemotherapy," Dr. Ben Solomon, a Medical Oncologist at the Peter MacCallum Cancer Centre in Australia, said in a presentation of the data.

"The DFS benefit was seen consistently across subgroups and an (improvement) in (central nervous system)-DFS was observed," Solomon said.

Significance

Among patients with NSCLC, approximately 4% to 5% will harbor an ALK rearrangement. These patients tend to be 55 years or younger, to not have a history of smoking, and to be at a higher risk of brain metastases — nearly half of patients with ALK alterations develop brain metastases.

Approximately 30% to 40% of patients with NSCLC will receive a diagnosis of resectable disease. Unfortunately, nearly half of patients with early-stage disease will experience disease recurrence after surgery, highlighting the importance of effective adjuvant options in this space.

The standard treatment approach following surgery is currently platinum-based chemotherapy for patients with stage 2B to 3A, ALK-positive disease; however, this modality is associated with modest improvements in survival outcomes. Similarly, immunotherapy approaches have not been fruitful for patients with resected, ALK-positive disease.

Alecensa already plays a role for certain patients with ALK-positive NSCLC. For patients with advanced disease who have not yet undergone resection, Alecensa is the preferred front-line regimen. Three distinct phase 3 trials have demonstrated significant progression-free survival benefits and intracranial control with Alecensa versus crizotinib in this setting. It is also associated with a high rate of intracranial activity. As of August 2023, it is estimated that more than 92,000 patients with ALK-positive disease have been treated with the oral TKI.

The current findings are the first to compare this agent against platinum-based chemotherapy in a population of ALK-positive patients in the adjuvant setting.

Secondary Outcomes

"In terms of the subgroup analysis, benefit in favor of (Alecensa) was seen across all the pre-defined subgroups evaluated, including stage and nodal status," Solomon emphasized in the presentation.

When looking at DFS by stage, the two-year results continued to favor Alecensa. For those with stage 1B disease (26 patients), stage 2 (92 patients) and stage 3A (139 patients) disease, respectively, the rates of DFS after 2 years were 92.3%, 95.6%, and 92.7% with Alecensa versus 71.6%, 66.3%, and 60.7%, respectively.

Therefore, the reduced risk of death or recurrence was 79% with stage 1B, 76% with stage 2 and 75% with 3A disease, respectively.

In addition, four patients receiving Alecensa versus 14 patients receiving chemotherapy in the intention-to-treat population experienced brain recurrence. The rate of central nervous system DFS at two years was 98.4% versus 85.8%, respectively. At three years, the rates were 95.5% versus 79.7%.

Regarding the agent's safety summary, the median duration of treatment was 23.9 months with Alecensa and 2.1 months with chemotherapy, leading to a longer safety follow-up time with the targeted treatment. The rate of any-grade side effects was 98% versus 93%, respectively. Of note, a higher percentage of patients receiving Alecensa needed to dose reduce because of a side effect (26% versus 10%) or interrupt treatment because of a side effect (27% versus 18%), although fewer needed to discontinue treatment overall (5% versus 13%).

The most common side effects reported with Alecensa were increased in blood creatine phosphokinase (indicating injury or stress to muscle tissue, the brain or the heart), constipation, and increases in aspartate aminotransferase and alanine aminotransferase (both of which indicate liver disease), as well as an increased in blood bilirubin (which may indicate liver dysfunction). In the chemotherapy arm, the most common side effects were nausea, constipation, anemia and decreased appetite.

"Adjuvant (Alecensa) was tolerable and in line with the known safety profile of (Alecensa)," Solomon concluded. "Adjuvant (Alecensa) represents an important new treatment strategy for patients with resected, stage 1B-3A, ALK-positive, NSCLC."

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Roche Lung Cancer Drug Reduced Risk Of Recurrence, Death In Late-Stage Trial

By Adria Calatayud

Roche Holding's Alecensa drug reduced the risk of disease recurrence or death in a phase 3 trial for a type of non-small cell lung cancer at an early stage, the company said Wednesday.

The Swiss pharmaceutical giant said a primary analysis of the study results showed Alecensa reduced the risk of disease recurrence or death by 76% compared with platinum-based chemotherapy, demonstrating a statistically significant and clinically meaningful improvement in disease-free survival.

The safety and tolerability of the drug in the trial were consistent with previous studies and no unexpected safety findings were observed, Roche said.

The company said it is conducting further analysis of overall survival estimates given that data were immature at this stage.

Roche will submit data from the trial to global health authorities, including the U.S. Food and Drug Administration and the European Medicines Agency, it said.

Write to Adria Calatayud at adria.Calatayud@dowjones.Com

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