Switch-Maintenance Gemcitabine After First-Line Chemotherapy In Patients With Malignant Pleural Mesothelioma

Malignant pleural mesothelioma is a rare but aggressive cancer of the pleural lining.

Malignant pleural mesothelioma accounted for 30,870 new cancer cases and 26,278 deaths worldwide in 2020.

In Egypt, Malignant pleural mesothelioma accounted for 337 new cases and 307 deaths in 2020.

Long-term exposure to asbestos is a well-established risk factor for Malignant pleural mesothelioma. It accounts for almost 80% of cases.

Malignant pleural mesothelioma is classified into three histologic subtypes: epithelioid, sarcomatoid, and biphasic. Epithelioid histology confers the most favorable prognosis and sarcomatoid the least.

The majority of patients with Malignant pleural mesothelioma present with breathlessness, chest pain or both. Other symptoms include fatigue, anorexia, weight loss, sweats and malaise.

Radiological imaging should be undertaken in all patients as it can provide valuable diagnostic and staging information. Further investigation of suspected Malignant pleural mesothelioma requires sampling of pleural fluid for biochemical and cytological examination. Biopsies are usually required to confirm the diagnosis and identify the histological sub-type.

Patients with Malignant pleural mesothelioma should be managed by an experienced multidisciplinary team. Treatment options include surgery, radiation therapy and chemotherapy.

Front line polychemotherapy is considered the standard of care, whereas single agent chemotherapy has shown limited efficacy with disappointing response rates.

A pivotal trial led to the establishment of Cisplatin and Pemetrexed as standard first line regimen for unresectable Malignant pleural mesothelioma.

A recent phase II trial from Cancer and Leukemia Group B showed that maintenance Pemetrexed after 4 to 6 cycles of doublet chemotherapy induction did not prolong progression free survival over placebo.

Adding Bevacizumab to first line platinum doublet resulted in an overall survival and progression free survival gain in the phase III French trial MAPS .Bevacizumab was continued as maintenance every three weeks following completion of six cycles of chemotherapy.

In a phase III trial NVALT 5 , Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy showed no benefit in time to progression.

First line Nivolumab plus Ipilimumab in phase III trial checkmate 743 provided significant and clinically meaningful improvements in overall survival versus standard of care chemotherapy.

Unfortunately, nearly all patients progress during or after first-line therapy, and no standard second line recommended treatments exist after platinum based regimen. Retreatment with pemetrexed, eventually associated with platinum compound, may be offered in patients who achieved durable disease control more than 6 months with first line chemotherapy.

Single agent chemotherapy with Vinorelbine or Gemcitabine is the preferred choice as second line treatment , mainly based on retrospective analyses or small phase II trials.

Inclusion criteria

• Being at least 18 years old
• Histologically or cytologically confirmed unresectable malignant pleural mesothelioma
• ECOG Performance status 0-2
• Completed at least four cycles of first line platinum (cisplatin or carboplatin) and pemetrexed combination chemotherapy before study entry
• No evidence of disease progression following first-line treatment based on radiological criteria.
• Adequate organ function is mandatory, defined as haemoglobin of at least 8.5 mg/dl, platelets of at least 100×10⁹ per L, and neutrophils of at least 1×10⁹/L.

Exclusion criteria

• Progression of disease after first line
• Pregnant females
• ECOG Performance 3-4
• Patients with sarcomatoid mesothelioma
• Patients who are candidates for curative surgery